Articles tagged as "Africa"

Age-disparate sexual partnerships - it’s more complicated than sugar daddies and blessers

Editor’s notes: Sugar daddies and blessers are men who provide gifts, money or other benefits to much younger women in exchange for sex.  These relationships are inevitably complex and are often seen as an important mode of transmission for HIV, particularly in Southern and East Africa.  Health education campaigns have raised the issue and aimed to discourage young women from having sex with older men.  However, the research on age-disparate relationships has been harder to interpret. Some studies show that having older partners is not necessarily an independent risk factor for HIV acquisition and others demonstrate a clear age difference in some couples where phylogenetics makes transmission seem very likely.  Nor do all age-disparate relationships involve sugar daddies or blessers.  Many women choose partners who are a few years older than themselves without such clear cut transactional motives.

This month saw Akulian et al. conclude that “age of sexual partner is a major risk factor for HIV acquisition” with frighteningly high rates of HIV incidence of 9.7 per 100 person years occurring among women aged 15-24 years old reporting partnerships with men aged 30-34 years old.  Yet the same research group (Harling et al.), in the same geographic community three years ago, concluded that “partner age disparity did not predict HIV acquisition” and cautioned against using resources for public health campaigns to reduce such partnerships.  A recent paper (de Oliveira et al.) from another research setting, also in KwaZulu-Natal, used phylogenetics to link isolates that were likely to be transmission pairs.  They too found that younger women (aged younger than 25 years) were more likely to have older male partners.  On average in the couples linked by phylogenetics the age difference was 8.7 years when the woman was younger than 25 but only 1.1 years when she was older than 25 years.

This month Schaefer et al. also demonstrated that in the Manicaland cohort in Zimbabwe, where incidence is somewhat lower than in KwaZulu-Natal, young women aged 15-24 years in partnerships with older men were likely to become  HIV positive .  They note that even the introduction of ART has not changed this observed finding, suggesting that the failure to reach men as effectively as we are reaching women, may be a significant reason for ongoing transmission.

The Akullian et al. paper used statistical techniques to smooth the observations from more than 1000 seroconversions observed in more than 25 000 person years of follow-up.  Harling et al. followed the cohort of women aged 15-29 years in the study area and observed 458 seroconversions over 5913 woman years of observation.  Although age-disparate relationships were common, age disparity was not an independent risk factor for HIV infection.  Akullian et al. explain that the real risk is from men aged 25-34 years.  Men in this age group are more likely to have recently acquired HIV, as it is the peak age group for incidence in males.  They are therefore likely to be particularly infectious with higher viral loads. They are also a group that has a low uptake of HIV testing and linkage to ART. 

The rates of ART use and HIV prevalence of older male partners for young women was explored by Evans et al. using data from the South African 2012 National HIV survey.  They found that male partners who were considerably older were more likely to be taking ART and so were likely to transmit fewer infections to their partners, which would tie in well with the Akullian et al. hypothesis of the highest risk being men aged 25-34 years.  The highest incidence is among young women, and these women are most likely to have partners in the 25-34 year old age band.  So we must be careful not to over-generalize.  This helps to explain the apparently differing results from these various studies.  If all age-disparate relationships are included in epidemiological studies, the important impact of transmission from recently infected and untreated 25-34 year old men to their younger female partners aged younger than 25 years may be diluted.

All these studies come from South Africa (usually KwaZulu-Natal) and Zimbabwe and so further detailed epidemiology supported by phylogenetics would be welcome from elsewhere.  Nonetheless, these various studies do translate into a clear message for action.  We need to work hard to find better ways to engage men aged 25-34 years, encourage them to get tested for HIV (see the HIV self-testing approaches above for instance) and link them to care and effective treatment much more efficiently than we are doing at present. 

Sexual partnership age pairings and risk of HIV acquisition in rural South Africa.

Akullian A, Bershteyn A, Klein D, Vandormael A, Bärnighausen T, Tanser F. AIDS. 2017 Jul 31;31(12):1755-1764. doi: 10.1097/QAD.0000000000001553.

Objective: To quantify the contribution of specific sexual partner age groups to the risk of HIV acquisition in men and women in a hyperendemic region of South Africa.

Design: We conducted a population-based cohort study among women (15-49 years of age) and men (15-55 years of age) between 2004 and 2015 in KwaZulu-Natal, South Africa.

Methods: Generalized additive models were used to estimate smoothed HIV incidence rates across partnership age pairings in men and women. Cox proportional hazards regression was used to estimate the relative risk of HIV acquisition by partner age group.

Results: A total of 882 HIV seroconversions were observed in 15  935 person-years for women, incidence rate = 5.5 per 100 person-years [95% confidence interval (CI), 5.2-5.9] and 270 HIV seroconversions were observed in 9372 person-years for men, incidence rate = 2.9 per 100 person-years (95% CI, 2.6-3.2). HIV incidence was highest among 15-24-year-old women reporting partnerships with 30-34-year-old men, incidence rate = 9.7 per 100 person-years (95% CI, 7.2-13.1). Risk of HIV acquisition in women was associated with male partners aged 25-29 years (adjusted hazard ratio; aHR = 1.44, 95% CI, 1.02-2.04) and 30-34 years (aHR = 1.50, 95% CI, 1.08-2.09) relative to male partners aged 35 and above. Risk of HIV acquisition in men was associated with 25-29-year-old (aHR = 1.72, 95% CI, 1.02-2.90) and 30-34-year-old women (aHR = 2.12, 95% CI, 1.03-4.39) compared to partnerships with women aged 15-19 years.

Conclusion: Age of sexual partner is a major risk factor for HIV acquisition in both men and women, independent of one's own age. Partner age pairings play a critical role in driving the cycle of HIV transmission.

Abstract Full-text [free] access

 

Do age-disparate relationships drive HIV incidence in young women? Evidence from a population cohort in rural KwaZulu-Natal, South Africa.

Harling G, Newell ML, Tanser F, Kawachi I, Subramanian SV, Bärnighausen T.J Acquir Immune Defic Syndr. 2014 Aug 1;66(4):443-51. doi: 10.1097/QAI.0000000000000198.

Background: Based on ethnographic investigations and mathematical models, older sexual partners are often considered a major risk factor for HIV for young women in sub-Saharan Africa. Numerous public health campaigns have been conducted to discourage young women from relationships with older men. However, longitudinal evidence relating sex partner age disparity to HIV acquisition in women is limited.

Methods: Using data from a population-based open cohort in rural KwaZulu-Natal, South Africa, we studied 15- to 29-year-old women who were HIV seronegative at first interview between January 2003 and June 2012 (n = 2444). We conducted proportional hazards analysis to establish whether the age disparity of women's most recent sexual partner, updated at each surveillance round, was associated with subsequent HIV acquisition.

Results: A total of 458 HIV seroconversions occurred over 5913 person-years of follow-up (incidence rate: 7.75 per 100 person-years). Age disparate relationships were common in this cohort; 37.7% of women reported a partner 5 or more years older than themselves. The age disparity of women's partners was not associated with HIV acquisition when measured either continuously [hazard ratio (HR) for 1-year increase in partner's age: 1.00, 95% confidence interval (CI): 0.97 to 1.03] or categorically (man ≥5 years older: HR, 0.98; 95% CI: 0.81 to 1.20; man ≥10 years older: HR, 0.98; 95% CI: 0.67 to 1.43). These results were robust to adjustment for known sociodemographic and behavioral HIV risk factors and did not vary significantly by women's age, marital status, education attainment, or household wealth.

Conclusions: HIV incidence in young women was very high in this rural community in KwaZulu-Natal. Partner age disparity did not predict HIV acquistion. Campaigns to reduce age-disparate sexual relationships may not be a cost-effective use of HIV prevention resources in this setting.

Abstract Full-text [free] access

 

Transmission networks and risk of HIV infection in KwaZulu-Natal, South Africa: a community-wide phylogenetic study.

de Oliveira T, Kharsany AB, Gräf T, Cawood C, Khanyile D, Grobler A, Puren A, Madurai S, Baxter C, Karim QA, Karim SS. Lancet HIV. 2017 Jan;4(1):e41-e50. doi: 10.1016/S2352-3018(16)30186-2. Epub 2016 Dec 1.

Background: The incidence of HIV infection in young women in Africa is very high. We did a large-scale community-wide phylogenetic study to examine the underlying HIV transmission dynamics and the source and consequences of high rates of HIV infection in young women in South Africa.

Methods: We did a cross-sectional household survey of randomly selected individuals aged 15-49 years in two neighbouring subdistricts (one urban and one rural) with a high burden of HIV infection in KwaZulu-Natal, South Africa. Participants completed structured questionnaires that captured general demographic, socioeconomic, psychosocial, and behavioural data. Peripheral blood samples were obtained for HIV antibody testing. Samples with HIV RNA viral load greater than 1000 copies per mL were selected for genotyping. We constructed a phylogenetic tree to identify clusters of linked infections (defined as two or more sequences with bootstrap or posterior support ≥90% and genetic distance ≤4·5%).

Findings: From June 11, 2014, to June 22, 2015, we enrolled 9812 participants, 3969 of whom tested HIV positive. HIV prevalence (weighted) was 59·8% in 2835 women aged 25-40 years, 40·3% in 1548 men aged 25-40 years, 22·3% in 2224 women younger than 25 years, and 7·6% in 1472 men younger than 25 years. HIV genotyping was done in 1589 individuals with a viral load of more than 1000 copies per mL. In 90 transmission clusters, 123 women were linked to 103 men. Of 60 possible phylogenetically linked pairings with the 43 women younger than 25 years, 18 (30·0%) probable male partners were younger than 25 years, 37 (61·7%) were aged 25-40 years, and five (8·3%) were aged 41-49 years: mean age difference 8·7 years (95% CI 6·8-10·6; p<0·0001). For the 92 possible phylogenetically linked pairings with the 56 women aged 25-40 years, the age difference dropped to 1·1 years (95% CI -0·6 to 2·8; p=0·111). 16 (39·0%) of 41 probable male partners linked to women younger than 25 years were also linked to women aged 25-40 years. Of 79 men (mean age 31·5 years) linked to women younger than 40 years, 62 (78·5%) were unaware of their HIV-positive status, 76 (96·2%) were not on antiretroviral therapy, and 29 (36·7%) had viral loads of more than 50 000 copies per mL.

Interpretation: Sexual partnering between young women and older men, who might have acquired HIV from women of similar age, is a key feature of the sexual networks driving transmission. Expansion of treatment and combination prevention strategies that include interventions to address age-disparate sexual partnering is crucial to reducing HIV incidence and enabling Africa to reach the goal of ending AIDS as a public health threat.

Abstract access 

 

Age-disparate relationships and HIV incidence in adolescent girls and young women: evidence from Zimbabwe.

Schaefer R, Gregson S, Eaton JW, Mugurungi O, Rhead R, Takaruza A, Maswera R, Nyamukapa C. AIDS. 2017 Jun 19;31(10):1461-1470. doi: 10.1097/QAD.0000000000001506.

Objective: Age-disparate sexual relationships with older men may drive high rates of HIV acquisition in young women in sub-Saharan Africa, but evidence is limited. We investigate the association between age-disparate relationships and HIV incidence in Manicaland, Zimbabwe.

Design: A general-population open-cohort study (six surveys) (1998-2013).

Methods: A total of 3746 young women aged 15-24 years participated in consecutive surveys and were HIV-negative at the beginning of intersurvey periods. Last sexual partner age difference and age-disparate relationships [intergenerational (≥10 years age difference) and intragenerational (5-9 years) versus age-homogeneous (0-4 years)] were tested for associations with HIV incidence in Cox regressions. A proximate determinants framework was used to explore factors possibly explaining variations in the contribution of age-disparate relationships to HIV incidence between populations and over time.

Results: About 126 HIV infections occurred over 8777 person-years (1.43 per 100 person-years; 95% confidence interval = 1.17-1.68). Sixty-five percent of women reported partner age differences of at least 5 years. Increasing partner age differences were associated with higher HIV incidence [adjusted hazard ratio (aHR) = 1.05 (1.01-1.09)]. Intergenerational relationships tended to increase HIV incidence [aHR = 1.78 (0.96-3.29)] but not intragenerational relationships [aHR = 0.91 (0.47-1.76)]. Secondary education was associated with reductions in intergenerational relationships [adjusted odds ratio (aOR) = 0.49 (0.36-0.68)]. Intergenerational relationships were associated with partners having concurrent relationships [aOR = 2.59 (1.81-3.70)], which tended to increase HIV incidence [aHR = 1.74 (0.96-3.17)]. Associations between age disparity and HIV incidence did not change over time.

Conclusion: Sexual relationships with older men expose young women to increased risk of HIV acquisition in Manicaland, which did not change over time, even with introduction of antiretroviral therapy.

Abstract  Full-text [free] access 

 

HIV prevalence and ART use among men in partnerships with 15-29 year old women in South Africa: HIV risk implications for young women in age-disparate partnerships.

Evans M, Maughan-Brown B, Zungu N, George G. AIDS Behav. 2017 Aug;21(8):2533-2542. doi: 10.1007/s10461-017-1741-6.

This study assesses whether men's ART use mitigates HIV-risk within age-disparate partnerships. Using data from the 2012 South African National HIV survey, we analyzed differences in HIV prevalence and ART use between men in age-disparate and age-similar partnerships with young women aged 15-29 using multiple logistic regression analyses. Within partnerships involving women 15-24 years old, men in age-disparate partnerships were more likely to be HIV-positive (5-9 year age-gap: aOR 2.8, 95%CI 1.4-5.2; p < 0.01; 10+ year age-gap: aOR 2.2, 95%CI 1.0-4.6; p < 0.05). Men in age-disparate partnerships who were 5-9 years older were significantly more likely to be HIV-positive and ART-naïve (aOR 2.4, 95%CI 1.2-4.8; p < 0.05), while this was not the case for men 10+ years older (aOR 1.5, 95%CI 0.7-3.6; p = 0.32). No evidence was found that 25-29 year old women were at greater HIV-risk in age-disparate partnerships. Our results indicate that young women aged 15-24 have a greater likelihood of exposure to HIV through age-disparate partnerships, but ART use among men 10+ years older could mitigate risk.

Abstract access 

 

Africa
South Africa, Zimbabwe
  • share
0 comments.

Some key considerations for surveys of key populations

Editor’s notes: A key challenge for epidemiological research involving key populations is to find a representative sample.  Whereas national surveys such as demographic health surveys (DHS) and PHIA can use the total population to create a sampling frame from which to draw individuals at random, researchers interested in key populations have to use a range of methods, all of which have limitations as well as strengths.  Internet and app-based surveys may accrue large numbers, but may have significant biases in terms of who chooses to answer such questionnaires.  Venue-based sampling allows data to be collected from people who happen to be at the venue at the same time as the researchers.  Respondent driven sampling has become increasingly popular as a method to reach individuals that might otherwise be hard to include in studies.  Increasingly sophisticated statistical methods have been developed to adjust estimates, and in particular their precision, according to characteristics of respondents found in the sample.

This month we have three respondent driven studies that highlight different methodological aspects as well as shedding light on key populations in Africa and Asia.  Hladik et al. conducted a major survey of female sex workers in Kampala, Uganda.  Unfortunately, it has taken some time for this study to be published, as the original questionnaires were completed in 2008/9 and it is plausible that many aspects of sex work have been changing over the past decade.  Nonetheless, the authors succeeded in enrolling almost 1000 female sex workers from the capital city using a respondent driven sampling approach.  The authors paid close attention to methods that could maximize the validity of the data they collected as well as ensuring that participants were protected.  Formative research laid out acceptable incentives to participate, as well as approaches to discuss sensitive or taboo areas and to ensure that all the women understood what was being asked in particular questions.  Finger scanners were used to generate unique identification numbers, so that women could be tracked during the study, and these files were subsequently deleted.  This approach was widely accepted, as it has been in many programmes offering services that benefit from a linked identifier.  However, any approach that creates identifiers for populations that are often discriminated or legislated against needs to be examined critically to ensure that any risks to participants are well understood, particularly for research that is not going to bring any direct benefits to the individual participants.  Although the study’s findings are not particularly surprising, they remind us that sex workers in Kampala need to remain a vital part of the HIV response.  Not only are they affected by a high prevalence of 33%, rising to 44% among those over 25 years old, but they are also subject to horribly high rates of violence including both rape and beating in up to one third of the women in the one month prior to the interview.  The study highlights particular factors that might help identify women in most need of HIV and other services.  Women with less education, who rely entirely on sex work for their income and who have never tested for HIV are all more likely to be HIV positive.

In nearby Malawi, Wirtz et al. point out that many respondent driven samples of key populations, such as that from Hladik et al., are only able to collect data from one particular city or region, and that this can lead to misinterpretation if the results are generalized to whole countries.  The authors conducted a large study of gay men and men who have sex with men in seven different communities across Malawi.  They found considerable heterogeneity leading to an overall estimate that the risk of HIV was approximately twice as high in gay men and men who have sex with men as in the general population of men of the same age.  The study managed to enrol a total of almost 2500 men through respondent driven sampling in the different districts.  However, this was at the expense of having to collect data over a considerable time period, with the study team moving from district to district.  As the authors acknowledge, the risk is that data collected in the most recent time period may not be equivalent to data collected four years previously.  The authors did find that the highest rates of HIV among gay men and men who have sex with men were not always where they have been presumed to be.  In particular tourist areas and some rural areas had higher rates than some of the cities that are usually the focus of key populations programmes.  Once again, the finding that so few gay men and men who have sex with men knew their status and were linked to treatment may not be surprising but is still shocking.  Only 1% of men found to be positive reported that they were aware of their status.  The authors point out the tension between public health and policy in a country where homosexuality is criminalized.  If HIV is to be prevented, this tension will need to be resolved.

The third respondent driven sampling study also highlights heterogeneity.  Verdery et al. used additional statistical methods to study the network characteristics of people who use drugs in two cities in the Philippines (Cebu and Mandaue).  The “small world” phenomenon explains how in more closed settings everyone knows everyone else, and among people who use drugs, many people form part of overlapping networks of needle sharing that allow for rapid propagation of infection.  Developing such methods could allow respondent driven samples to yield greater insights in to the epidemiology of HIV in key populations.  However, issues of representation both of the sample interviewed and of the broader geographic population of interest will remain important.  Quantitative research is certainly essential to understand the population sizes of key populations, and their prevalence, incidence and risk factors of HIV infection.  However, research into policy formation; social science research to understand the larger context of HIV and implementation science to determine how better to offer services that engage individuals in HIV testing and care remain a high priority. 

Burden and characteristics of HIV infection among female sex workers in Kampala, Uganda - a respondent-driven sampling survey

Hladik W, Baughman AL, Serwadda D, Tappero JW, Kwezi R, Nakato ND, Barker J. BMC Public Health. 2017 Jun 10;17(1):565. doi: 10.1186/s12889-017-4428-z.

Background: Sex workers in Uganda are at significant risk for HIV infection. We characterized the HIV epidemic among Kampala female sex workers (FSW).

Methods: We used respondent-driven sampling to sample FSW aged 15+ years who reported having sold sex to men in the preceding 30 days; collected data through audio-computer assisted self-interviews, and tested blood, vaginal and rectal swabs for HIV, syphilis, neisseria gonorrhea, chlamydia trachomatis, and trichomonas vaginalis.

Results: A total of 942 FSW were enrolled from June 2008 through April 2009. The overall estimated HIV prevalence was 33% (95% confidence intervals [CI] 30%-37%) and among FSW 25 years or older was 44%. HIV infection is associated with low levels of schooling, having no other work, never having tested for HIV, self-reported genital ulcers or sores, and testing positive for neisseria gonorrhea or any sexually transmitted infections (STI). Two thirds (65%) of commercial sex acts reportedly were protected by condoms; one in five (19%) FSW reported having had anal sex. Gender-based violence was frequent; 34% reported having been raped and 24% reported having been beaten by clients in the preceding 30 days.

Conclusions: One in three FSW in Kampala is HIV-infected, suggesting a severe HIV epidemic in this population. Intensified interventions are warranted to increase condom use, HIV testing, STI screening, as well as antiretroviral treatment and pre-exposure prophylaxis along with measures to overcome gender-based violence.

Abstract  Full-text [free] access

 

Geographical disparities in HIV prevalence and care among men who have sex with men in Malawi: results from a multisite cross-sectional survey.

Wirtz AL, Trapence G, Kamba D, Gama V, Chalera R, Jumbe V, Kumwenda R, Mangochi M, Helleringer S, Beyrer C, Baral S. Lancet HIV. 2017 Jun;4(6):e260-e269. doi: 10.1016/S2352-3018(17)30042-5. Epub 2017 Feb 28.

Background: Epidemiological assessment of geographical heterogeneity of HIV among men who have sex with men (MSM) is necessary to inform HIV prevention and care strategies in the more generalised HIV epidemics across sub-Saharan Africa, including Malawi. We aimed to measure the HIV prevalence, risks, and access to HIV care among MSM across multiple localities to better inform HIV programming for MSM in Malawi.

Methods: Between Aug 1, 2011, and Sept 13, 2014, we recruited MSM into cross-sectional research via respondent-driven sampling (RDS) in seven districts of Malawi. RDS and site weights were used to estimate national HIV prevalence and engagement in care and in multilevel regression models to identify correlates of prevalent HIV infection. The comparative prevalence ratio of HIV among MSM relative to adult men was calculated by use of direct age-stratification.

Findings: 2453 MSM were enrolled with a population HIV prevalence of 18·2% (95% CI 15·5-21·2), as low as 4·1% (2·2-7·6) in Mzuzu and as high as 24·5% (19·5-30·3) in Mulanje. The comparative HIV prevalence ratio was 2·52 when comparing MSM with the adult male population. Age-stratified HIV prevalence showed early onset of infection with 11·8% (95% CI 7·3-18·4) of MSM aged 18-19 years HIV infected. Factors positively associated with HIV infection included being aged 21-30 years and reporting female or transgender identity. Among HIV infected MSM, less than 1% reported ever being diagnosed with HIV infection (0·9%, 95% CI 0·4-2·5) and initiated antiretroviral treatment (0·2%, 0·2-0·3).

Interpretation: HIV disproportionately affects MSM in Malawi with disparities sustained across the HIV care continuum. These issues are geographically heterogeneous and begin among young MSM, supporting geographically focused and age-specific approaches to confidential HIV testing with linkage to HIV services. 

Abstract access 

 

Social network clustering and the spread of HIV/AIDS among persons who inject drugs in two cities in the Philippines

Verdery AM, Siripong N, Pence BW. J Acquir Immune Defic Syndr. 2017 Sep 1;76(1):26-32. doi: 10.1097/QAI.0000000000001485. Epub 2017 Jun 22.

Introduction: The Philippines has seen rapid increases in HIV prevalence among people who inject drugs. We study two neighboring cities where a linked HIV epidemic differed in timing of onset and levels of prevalence. In Cebu, prevalence rose rapidly from under 1% to 54% between 2009 and 2011 and remained high through 2013. In nearby Mandaue, HIV remained below 4% through 2011 then rose rapidly to 38% by 2013.

Objectives: We hypothesize that infection prevalence differences in these cities may owe to aspects of social network structure, specifically levels of network clustering. Building on prior research, we hypothesize that higher levels of network clustering are associated with greater epidemic potential.

Methods: Data were collected with respondent-driven sampling among males who inject drugs in Cebu and Mandaue in 2013. We first examine sample composition using estimators for population means. We then apply new estimators of network clustering in respondent-driven sampling data to examine associations with HIV prevalence.

Results: Samples in both cities were comparable in terms of composition by age, education, and injection locations. Dyadic needle sharing levels were also similar between the two cities, but network clustering in the needle sharing network differed dramatically. We found higher clustering in Cebu than Mandaue, consistent with expectations that higher clustering is associated with faster epidemic spread.

Conclusion: This paper is the first to apply estimators of network clustering to empirical respondent-driven samples, and it offers suggestive evidence that researchers should pay greater attention to network structure's role in HIV transmission dynamics.

Abstract access

Africa, Asia
Malawi, Philippines, Uganda
  • share
0 comments.

90-90-90: a clear roadmap for HIV treatment. But each 90 brings with it opportunities and challenges

Editor’s notes: The discovery of effective antiretroviral therapy (ART) will go down in history as the greatest success of biomedical science of the past decades.  Landmark studies have shown that the earlier people living with HIV start ART, not only is their clinical outlook improved, but also their likelihood of transmitting infection to their sexual partners falls dramatically.  People who take their ART effectively and in whom the virus is suppressed to undetectable levels are no longer infectious.  A massive public health and social justice response has led to unprecedented scale up of this miraculous treatment.  There is widespread adoption of the UNAIDS 90-90-90 treatment target.  The target is easy to recite: 90% of people living with HIV know their status; 90% of people who know their status are on ART and 90% of people taking ART have suppressed their viral load.  Many mathematical models show that if these targets are achieved, there should be a substantial impact on the trajectory of the epidemic with a large reduction in new HIV infections and HIV-related deaths, leading to huge cost-savings in the future.

Several large community based studies have been established to examine both the necessary processes to reach these goals and the impact at community level of the wider coverage with effective ART.  We have commented in previous editions on the ANRS Treatment as Prevention (TasP) study in rural Kwazulu-Natal and on papers from the SEARCH study in rural Kenya and Uganda.  Not surprisingly, given the different contexts, approaches, methods and definitions, the studies each shed light on different aspects of the 90-90-90 target.

This month, there are two new papers from the PopART (HPTN071) study, along with an accompanying commentary from the TasP study team.  PopART is the largest of the large community randomized studies of the universal test and treat approach, nested within a broader combination prevention package.  The population covered by the trial is around one million people living in largely urban or peri-urban communities in Zambia and the Western Cape province of South Africa.  The approach used in two of the three arms of the trial, is to deliver HIV testing and other prevention services by means of community health workers.  These so called CHiPs (Community HIV care Providers) also encourage linkage of people either known to be or newly found to be living with HIV to the local government health facilities, where ART is started regardless of CD4 count in one arm of the study, or in line with government guidelines (which is now also regardless of CD4 count in both countries) in the other. In the third arm of the trial, there are no CHiPs and HIV testing and linkage to treatment is performed by routine services, with treatment also offered to all, regardless of CD4 count.

The papers in this month’s edition cover only the four Zambian communities receiving the most intensive package during the first year of the intervention. Shanaube and colleagues focus on the first 90, while Hayes and colleagues focus on the second 90.  The overall conclusion is that the CHiPs approach leads to a very high uptake of HIV testing, but that linkage to care still takes longer than expected.  However, there is a wealth of detail in both the process and the ways to measure these apparently straightforward statistics.  When the CHiPs actually see people, acceptance of HIV testing is very high, unless people have recently had an HIV test.  Even then, almost three quarters of women are happy to have another test four to six months after their most recent negative test, whereas for men, there is somewhat more reluctance.  The main challenges for the CHiPs are that people may need more than one visit to decide to test and that men are often not at home, despite multiple visits and scheduled appointments.  Furthermore, as Iwuju and Newell point out in their slightly pessimistic commentary, people move around and migration makes it hard to define a reliable denominator (a challenge also faced by the SEARCH team in Uganda and Kenya).  Around 20% of the people who knew they were HIV positive were not able to be seen at one year follow-up, so it is not possible to know whether they were linked to care or not.  The TasP study also found that the second 90 was the real challenges, with a very high coverage of HIV testing, but not enough linkage to lead to a reduction in incidence at the community level.

The PopART study is ongoing, and recent presentations suggest that with time, a larger proportion of people are indeed linking to care.  The lesson may be that it requires ongoing and continuing support in an urban and peri-urban community to achieve high levels of coverage.  We await eagerly the next instalments and final results demonstrating whether there is a wider public health impact which will not be available before 2019!

These huge longitudinal studies also remind us that the 90-90-90 target is defined as cross-sectional measurements, and does not take into account directly the length of time that it takes to start treatment or to become virally supressed.  The information from large cross-sectional studies, such as ICAP and PEPFAR’s population-based HIV impact assessments (PHIA) give a direct measurement of 90-90-90.  However, in contrast to PopART and the other community-based studies, gives no insight into the dynamics of the processes through which people decide to get tested, link to care and remain in care.

McCreesh and colleagues used an individual-based mathematical model of the flow through testing, linkage to treatment and retention based on data from Uganda and using a novel method of calibration.  They show that removing the CD4 threshold (as is recommended by WHO and the UNAIDS 90-90-90 target) is very likely to be the most cost-effective approach to reduce the burden of HIV over the years up to 2030.  However, they also found that their model predicts that efforts to improve linkage to and retention in care are likely to be more cost-effective than increased coverage of testing in Uganda.  This is in part because many Ugandans already know their HIV status as a result of previous efforts, so it should not be taken as a general recommendation not to work to improve the first 90 as well as the second two!  The authors state clear conclusions: “Our results strongly suggest that an increase in the rates of HIV testing in the general population in Uganda ….. should not be prioritized above interventions to improve linkage to, and retention in, care…..  In Uganda, interventions to improve retention in and movement through the HIV care pathway should be prioritized over case finding interventions in the general population.”

In rural Kwazulu-Natal, the challenge of retention among populations that are by necessity mobile was also shown in a study by Arnesen and colleagues.  In this study of risk factors for people on ART being lost to follow up they found that more than one quarter of the 3242 people on the treatment register in 15 primary care clinics were thought to be lost.  However, the authors found that one-third of these people labelled as lost were in fact taking treatment at another clinic.  As in other similar studies men were more likely to discontinue treatment, as were people with advanced immunosuppression (who are at high risk of dying in the absence of treatment) and being on ART for less than six months. This is a useful reminder of priorities.  Providing more support to men, and the sickest patients, maintaining closer supervision for the first year, might lead to better programme outcomes and (as predicted by the Ugandan model) save money in the medium term.

By comparison, a large records-based study in the United States of America by Youn and colleagues examined time trends in retention on treatment (persistence in the authors’ terminology).  The author used insurance claims for prescriptions for ART and for other medicines for heart disease, hypertension or diabetes taken regularly over a long time by both HIV positive and HIV-negative people.  They were able to examine persistence in over 40 000 people living with HIV starting treatment in 2001-2003 (when ART was more cumbersome and more toxic) compared to 2004-2006 and 2007-2010.  Persistence improved dramatically over this time period for ART, but hardly changed at all for the other medicines studied.  This demonstrates that the changes were not merely secular trends in the likelihood of remaining on treatment.  Interestingly, in people living with HIV, persistence on the non-HIV related medicines also improved, suggesting that HIV care provided additional benefits in terms of retention and adherence to medicines that went beyond ART. 

There was also good news from Australia, where Medland and colleagues used records from the two largest HIV treatment clinics in the state of Victoria to examine time trends in the delay from HIV diagnosis to starting ART.  Among 729 people started on ART, the proportion of patient in care and on ART within one year of diagnosis increased from 43.4% to 78.9% from 2011 to 2014.  By 2014, 50% of people were starting ART within 77 days of being diagnosed.  The authors point out that this is a key measurement of programme effectiveness that is not routinely captured.  Nor does it form part of the 90-90-90 targets.  Of course, it is important to remember that the period prior to HIV diagnosis is probably even more important in terms of risks of transmission, as there have been numerous studies showing that people who know their HIV status are less likely to transmit HIV.  So we really need to know the period from infection to HIV diagnosis, as well as the time from diagnosis to treatment, and perhaps also the time to become virally supressed.  Viral suppression can take months or even more than a year depending on an individual’s initial virological and immunological state and variations in response to treatment as well as with the choice of ART regimen.

Despite massive scale up of ART, there are still many people living with HIV who present to services late with a CD4 count of <200 cells per ml.  A recent report in MMWR, showed that in 10 PEPFAR supported countries, there are still as many as one third of people presenting late.  Many of these people have opportunistic infections that have characterised HIV infection since the earliest days of the AIDS epidemic.  Botswana has made huge progress towards 90-90-90, but Tenforde and colleagues show that cryptococcal meningitis is still a major health problem.  They were able to collect laboratory based data over the past decade, as well as more detailed records from the two largest referral centres.  Although the number of cases of cryptococcal meningitis has halved since 2004, when the scale up of ART in Botswana really got going, the two referral hospitals still see more than 150 cases per year.  Mortality is still horribly high.  Overall, the authors explored data from more than 5000 episodes of cryptococcal meningitis in 4702 individuals over the period 2004-2014.  For people who could be linked to their clinical medical records, they demonstrate that the risk rises dramatically as the CD4 count falls – people with a CD4 count of < 50 cells per ml have an incidence of around 2000/100 000 person years, whereas the rates of people with 50-100 or 100-200 cells per ml are around 350 and 80 respectively.  More than 90% of the cases identified occurred in people whose CD4 cell count was <200 cells per ml.  As other studies might have predicted, men are more affected, as they tend to present to services later.  The most useful medicines for cryptococcal meningitis, i.e., liposomal Amphotericin and 5 flucytosine, remain too expensive or not available in most African countries.  Not only do we need to bring the prices of these commodities down to affordable levels, but we also need continued efforts to engage men (and other populations who get left behind) earlier in the course of their HIV infection.

The improvements in overall survival and life expectancy for people living with HIV if they have access to effective treatments are well known.  A large collaborative study (the ART Cohort Collaboration) has brought together 18 European and North American cohorts in order to look at the mortality experienced in the first years after starting ART.  They found the biggest improvements in people who started treatment in the last period that they studied (2008-2010).  There were also greater changes in mortality in the second and third years after starting ART.  Even so, they conclude that life expectancy is still not as good as that of HIV negative people.  Previous studies have sometimes been biased towards people who survive longer, partly through not including as many people in the first year after ART when mortality is at its highest.  They propose that much of the improvement seen is due to newer drugs and more options for treatment failure.  They therefore caution against the temptation to save money on cheaper generics as they become available for older medicines that may be less palatable or less effective.

What works-reaching universal HIV testing: lessons from HPTN 071 (PopART) trial in Zambia

Shanaube K, Schaap A, Floyd S, Phiri M, Griffith S, Chaila J, Bock P, Hayes R, Fidler S, Ayles H; HPTN 071 (PopART) Study Team. AIDS. 2017 Jul 17;31(11):1555-1564. doi: 10.1097/QAD.0000000000001514..

Objective: To determine the uptake of home-based HIV counselling and testing (HCT) in four HPTN071 (PopART) trial communities (implementing a 'full' combination HIV prevention package that includes universal HIV testing and treatment) in Zambia. We also explore factors associated with uptake of HCT in these communities.

Design: HPTN071 (PopART) is a 3-arm community-randomized trial in 12 communities in Zambia and 9 communities in South Africa evaluating the impact of a combination HIV prevention package, including universal HIV testing and treatment, on HIV incidence.

Methods: Using a door-to-door approach that includes systematically re-visiting households, individuals were offered participation in the intervention and verbal consent was obtained. Data were analysed for the first 18 months of the intervention, December 2013 to June 2015 for individuals 18 years and older.

Results: Among 121 130 enumerated household members, 101 102 (83.5%) accepted the intervention. HCT uptake was 72.2% (66 894/92 612), similar by sex but varied across communities. HCT uptake was associated with younger age, sex, community, being symptomatic for TB and STI and longer time since previous HIV test. Knowledge of HIV status due to the intervention increased by 36% overall and by 66% among HIV positives; the highest impact was among 18-24 year olds.

Conclusion: Overall acceptance of HIV-testing through offering a door-to-door-based combination HIV prevention package was 72.2%. The intervention increased knowledge of HIV status from 50% to 90%. However, challenges still remain and a one-off intervention is unlikely to be successful but will require repeated visits and multiple strategies.

Abstract access

A universal testing and treatment intervention to improve HIV control: One-year results from intervention communities in Zambia in the HPTN 071 (PopART) cluster-randomised trial

Hayes R, Floyd S, Schaap A, Shanaube K, Bock P, Sabapathy K, Griffith S, Donnell D, Piwowar-Manning E, El-Sadr W, Beyers N, Ayles H, Fidler S; HPTN 071 (PopART) Study Team. PLoS Med. 2017 May 2;14(5):e1002292. doi: 10.1371/journal.pmed.1002292. eCollection 2017 May.

Objective: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets require that, by 2020, 90% of those living with HIV know their status, 90% of known HIV-positive individuals receive sustained antiretroviral therapy (ART), and 90% of individuals on ART have durable viral suppression. The HPTN 071 (PopART) trial is measuring the impact of a universal testing and treatment intervention on population-level HIV incidence in 21 urban communities in Zambia and South Africa. We report observational data from four communities in Zambia to assess progress towards the UNAIDS targets after 1 y of the PopART intervention.

Methods and Findings: The PopART intervention comprises annual rounds of home-based HIV testing delivered by community HIV-care providers (CHiPs) who also support linkage to care, ART retention, and other services. Data from four communities in Zambia receiving the full intervention (including immediate ART for all individuals with HIV) were used to determine proportions of participants who knew their HIV status after the CHiP visit; proportions linking to care and initiating ART following referral; and overall proportions of HIV-infected individuals who knew their status (first 90 target) and the proportion of these on ART (second 90 target), pre- and post-intervention. We are not able to assess progress towards the third 90 target at this stage of the study. Overall, 121 130 adults (59 283 men and 61 847 women) were enumerated in 46 714 households during the first annual round (December 2013 to June 2015). Of the 45 399 (77%) men and 55 703 (90%) women consenting to the intervention, 80% of men and 85% of women knew their HIV status after the CHiP visit. Of 6197 HIV-positive adults referred by CHiPs, 42% (95% CI: 40%-43%) initiated ART within 6 mo and 53% (95% CI: 52%-55%) within 12 mo. In the entire population, the estimated proportion of HIV-positive adults who knew their status increased from 52% to 78% for men and from 56% to 87% for women. The estimated proportion of known HIV-positive individuals on ART increased overall from 54% after the CHiP visit to 74% by the end of the round for men and from 53% to 73% for women. The estimated overall proportion of HIV-positive adults on ART, irrespective of whether they knew their status, increased from 44% to 61%, compared with the 81% target (the product of the first two 90 targets). Coverage was lower among young men and women than in older age groups. The main limitation of the study was the need for assumptions concerning knowledge of HIV status and ART coverage among adults not consenting to the intervention or HIV testing, although our conclusions were robust in sensitivity analyses.

Conclusions: In this analysis, acceptance of HIV testing among those consenting to the intervention was high, although linkage to care and ART initiation took longer than expected. Knowledge of HIV-positive status increased steeply after 1 y, almost attaining the first 90 target in women and approaching it in men. The second 90 target was more challenging, with approximately three-quarters of known HIV-positive individuals on ART by the end of the annual round. Achieving higher test uptake in men and more rapid linkage to care will be key objectives during the second annual round of the intervention.

Abstract  Full-text [free] access

Universal test, treat, and keep: improving ART retention is key in cost-effective HIV control in Uganda

McCreesh N, Andrianakis I, Nsubuga RN, Strong M, Vernon I, McKinley TJ, Oakley JE, Goldstein M, Hayes R, White RG. BMC Infect Dis. 2017 May 3;17(1):322. doi: 10.1186/s12879-017-2420-y.

Background: With ambitious new UNAIDS targets to end AIDS by 2030, and new WHO treatment guidelines, there is increased interest in the best way to scale-up ART coverage. We investigate the cost-effectiveness of various ART scale-up options in Uganda.

Methods: Individual-based HIV/ART model of Uganda, calibrated using history matching. 22 ART scale-up strategies were simulated from 2016 to 2030, comprising different combinations of six single interventions (1. increased HIV testing rates, 2. no CD4 threshold for ART initiation, 3. improved ART retention, 4. increased ART restart rates, 5. improved linkage to care, 6. improved pre-ART care). The incremental net monetary benefit (NMB) of each intervention was calculated, for a wide range of different willingness/ability to pay (WTP) per DALY averted (health-service perspective, 3% discount rate).

Results: For all WTP thresholds above $210, interventions including removing the CD4 threshold were likely to be most cost-effective. At a WTP of $715 (1 × per-capita-GDP) interventions to improve linkage to and retention/re-enrolment in HIV care were highly likely to be more cost-effective than interventions to increase rates of HIV testing. At higher WTP (> ~ $1690), the most cost-effective option was 'Universal Test, Treat, and Keep' (UTTK), which combines interventions 1-5 detailed above.

Conclusion: Our results support new WHO guidelines to remove the CD4 threshold for ART initiation in Uganda. With additional resources, this could be supplemented with interventions aimed at improving linkage to and/or retention in HIV care. To achieve the greatest reductions in HIV incidence, a UTTK policy should be implemented.

Abstract  Full-text [free] access

Predictors of loss to follow-up among patients on ART at a rural hospital in KwaZulu-Natal, South Africa.

Arnesen R, Moll AP, Shenoi SV. PLoS One. 2017 May 24;12(5):e0177168. doi: 10.1371/journal.pone.0177168. eCollection 2017

Introduction: Improved HIV outcomes as a result of expanded antiretroviral therapy (ART) access is threatened by increasing rates of loss to follow up (LTFU) among those on ART, largely reported in urban populations. Some reports suggest that LTFU rates are overestimated due to patient movement to other facilities and inadequate medical records.

Study Objective: To define the proportion disengaging from HIV care as well as the characteristics of those LTFU in order to design and implement appropriate interventions to increase retention.

Methods: We performed a retrospective review of patients who discontinued ART at a central hospital ART clinic in rural South Africa and compared with patients receiving care at the 15 primary health clinics (PHCs) to determine the true proportion of those who were LTFU. We also compared those who discontinued ART with those who did not at the central hospital ART clinic to determine predictors of loss to follow up.

Results: Among 3242 patients on ART, 820 were originally marked as LTFU. Among all patients, 272 (8.4%) were found at a clinic on treatment, 56 (1.7%) were found at a clinic from which they had since discontinued treatment, and 10 (0.3%) returned to care between June and July 2016, leaving 475 (14.7%) unaccounted for and thus categorized as 'true' LTFU. Factors found to be associated with discontinuation include being male, age 18-35, having a CD4 count under 200 cells/μL, and being on ART for under six months.

Conclusions: Young men with low CD4 counts early after ART initiation are at highest risk of ART disengagement in this rural South African HIV clinic. Novel interventions targeting this group are needed to improve retention in care.

Abstract  Full-text [free] access

Ten-year trends in anti-retroviral therapy persistence among US Medicaid beneficiaries, 2001-2010

Youn B, Shireman TI, Lee Y, Galárraga O, Rana AI, Justice AC, Wilson IB. AIDS. 2017 May 16. doi: 10.1097/QAD.0000000000001541. [Epub ahead of print]

Objective: Whether the rate of HIV antiretroviral therapy (ART) persistence has improved over time in the U.S. is unknown. We examined ART persistence trends between 2001 and 2010, using non-HIV medications as a comparator.

Methods: We conducted a retrospective cohort study using Medicaid claims. We defined persistence as the duration of treatment from the first to the last fill date before a 90-day permissible gap, and used Kaplan-Meier curves and Cox proportional hazard models to assess crude and adjusted non-persistence. The secular trends of ART persistence in 43 598 HIV patients were compared with the secular trends of persistence with angiotensin-converting enzyme inhibitors (ACE) or angiotensin receptor blockers (ARB), statins, and metformin in (1) non-HIV-infected patients and (2) subgroups of HIV patients who started these control medications while using ART.

Results: Median time to ART non-persistence increased from 23.9 months in 2001-2003 to 35.4 months in 2004-2006, and was not reached for those starting ART in 2007-2010. In adjusted models, ART initiators in 2007-2010 had 11% decreased hazards of non-persistence compared with those who initiated in 2001-2003 (p < 0.001). For non-HIV patients initiating ACE/ARB, statins, and metformin, the hazard ratios (HR) for non-persistence comparing 2007-2010 to 2001-2003 were 1.07, 0.94, and 1.02, respectively (all p < 0.001). For HIV patients initiating the three control medications, the HRs of non-persistence comparing 2007-2010 to 2001-2003 were 0.71, 0.65, and 0.63, respectively (all p < 0.001).

Conclusions: Persistence with ART improved between 2001 and 2010. Persistence with control medications improved at a higher rate among HIV patients using ART than HIV-negative controls.

Abstract

Time from HIV diagnosis to commencement of antiretroviral therapy as an indicator to supplement the HIV cascade: Dramatic fall from 2011 to 2015

Medland NA, Chow EP, McMahon JH, Elliott JH, Hoy JF, Fairley CK. PLoS One. 2017 May 16;12(5):e0177634. doi: 10.1371/journal.pone.0177634. eCollection 2017.

Introduction:  The HIV care cascade is increasingly used to evaluate HIV treatment programs at the population level. However, the cascade indicators lack the ability to show changes over time, which reduces their utility to guide health policy. Alternatives have been proposed but are complex or result in a delay in results. We propose a new indicator of ART uptake, the time from HIV diagnosis to commencement of ART, and compare it to the existing cascade indicator of proportion of patients on treatment and the WHO proposed cohort cascade indicator of proportion of patients on treatment within one year of diagnosis.

Methods and Materials: Records from patients from the two largest HIV treatment centres in the state of Victoria, Australia (Melbourne Sexual Health Centre and The Alfred Hospital Department of Infectious Diseases) from 2011 to 2015 were extracted. The intervals between date of diagnosis, entry into care and initiation of ART were compared.

Results and Discussion: From 2011 to 2015 the proportion of in-care patients who were on ART rose from 87% to 93% (p<0.0001). From 2011 to 2014, the proportion of patients in care and on ART within one year of diagnosis increased from 43.4% to 78.9% (p = 0.001). The median time from diagnosis to ART fell from 418 days (IQR: 91-1176) to 77 days (IQR: 39-290)(p<0.001) by calendar year in which ART was commenced.

Conclusions: From 2011 to 2015 there were substantial and clinically important falls in the median time from diagnosis to commencing ART in those that commenced ART. The size of this dramatic change was not apparent when only reporting the proportion of patients on ART. Time to ART is a useful indicator and can be used to supplement existing cascade indicators in measuring progress toward universal ART coverage.

Abstract  Full-text [free] access

Trends in prevalence of advanced HIV disease at antiretroviral therapy enrollment — 10 countries, 2004–2015

Auld AF, Shiraishi RW, Oboho I, Ross C, Bateganya M, Pelletier V, Dee J, Francois K, Duval N, Antoine M, Delcher C, Desforges G, Griswold M, Domercant JW, Joseph N, Deyde V, Desir Y, Van Onacker JD, Robin E, Chun H, Zulu I, Pathmanathan I, Dokubo EK, Lloyd S, Pati R, Kaplan J, Raizes E, Spira T, Mitruka K, Couto A, Gudo ES, Mbofana F, Briggs M, Alfredo C, Xavier C, Vergara A, Hamunime N, Agolory S, Mutandi G, Shoopala NN, Sawadogo S, Baughman AL, Bashorun A, Dalhatu I, Swaminathan M, Onotu D, Odafe S, Abiri OO, Debem HH, Tomlinson H, Okello V, Preko P, Ao T, Ryan C, Bicego G, Ehrenkranz P, Kamiru H, Nuwagaba-Biribonwoha H, Kwesigabo G, Ramadhani AA, Ng'wangu K, Swai P, Mfaume M, Gongo R, Carpenter D, Mastro TD, Hamilton C, Denison J, Wabwire-Mangen F, Koole O, Torpey K, Williams SG, Colebunders R, Kalamya JN, Namale A, Adler MR, Mugisa B, Gupta S, Tsui S, van Praag E, Nguyen DB, Lyss S, Le Y, Abdul-Quader AS, Do NT, Mulenga M, Hachizovu S, Mugurungi O, Barr BAT, Gonese E, Mutasa-Apollo T, Balachandra S, Behel S, Bingham T, Mackellar D, Lowrance D, Ellerbrock TV.MMWR Morb Mortal Wkly Rep. 2017 Jun 2;66(21):558-563. doi: 10.15585/mmwr.mm6621a3.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies. To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694 138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

Abstract  Full-text [free] access

Advanced HIV disease in Botswana following successful antiretroviral therapy rollout: Incidence of and temporal trends in cryptococcal meningitis

Tenforde MW, Mokomane M, Leeme T, Patel RK, Lekwape N, Ramodimoosi C, Dube B, Williams EA, Mokobela KO, Tawanana E, Pilatwe T, Hurt WJ, Mitchell H, Banda DL, Stone H, Molefi M, Mokgacha K, Phillips H, Mullan PC, Steenhoff AP, Mashalla Y, Mine M, Jarvis JN. Clin Infect Dis. 2017 May 13. doi: 10.1093/cid/cix430. [Epub ahead of print].

Background: Botswana has a well-developed antiretroviral therapy (ART) program which serves as a regional model. With wide ART availability, the burden of advanced HIV and associated opportunistic infections would be expected to decline. We performed a nationwide surveillance study to determine the national incidence of cryptococcal meningitis, and describe characteristics of cases 2000-2014 and temporal trends at two national referral hospitals.

Methods: Cerebrospinal fluid data from all 37 laboratories performing meningitis diagnostics in Botswana were collected 2000-2014 to identify cases of cryptococcal meningitis. Basic demographic and laboratory data were recorded. Complete national data from 2013-2014 were used to calculate national incidence using UNAIDS population estimates. Temporal trends in cases were derived from national referral centers 2004-2014.

Results: 5296 episodes of cryptococcal meningitis were observed in 4702 individuals; 60.6% were male, and median age was 36 years. Overall 2013-2014 incidence was 17.8 cases/100 000 person-years (95%CI 16.6 - 19.2). In the HIV-infected population, incidence was 96.8 cases/100 000 person-years (95%CI 90.0 - 104.0); male predominance was seen across CD4 strata. At national referral hospitals, cases decreased 2007-2009 but stabilized 2010-2014.

Conclusions: Despite excellent ART coverage in Botswana, there is still a substantial burden of advanced HIV, with 2013-2014 incidence of cryptococcal meningitis comparable to pre-ART era rates in South Africa. Our findings suggest a key population of individuals, often men, are developing advanced disease and associated opportunistic infections due to a failure to effectively engage in care, highlighting the need for differentiated care models.

Abstract

Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies

Trickey A, May MT, Vehreschild JJ, Obel N, Gill MJ, Crane HM, Boesecke C, Patterson S, Grabar S, Cazanave C, Cavassini M, Shepherd L, Monforte AD, van Sighem A, Saag M, Lampe F, Hernando V, Montero M, Zangerle R, Justice AC, Sterling T, Ingle SM, Sterne JAC (Antiretroviral Therapy Cohort Collaboration). Lancet HIV. 2017 May 10. pii: S2352-3018(17)30066-8. doi: 10.1016/S2352-3018(17)30066-8. [Epub ahead of print]

Background: Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013.

Methods: We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996-99, 2000-03 [comparator], 2004-07, 2008-10). We estimated life expectancy by calendar period of initiation of ART.

Findings: 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008-10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000-03 (adjusted HR 0·71, 95% CI 0·61-0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008-10 than in those who started in 2000-03 (0·57, 0·49-0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008-10 (vs 2000-03) in the first year (0·48, 0·34-0·67) and second and third years (0·29, 0·21-0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men.

Interpretation: Even in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements.

Abstract  Full-text [free] access

 

Africa, Asia, Europe, Northern America, Oceania
  • share
0 comments.

How are we going to get to our prevention targets? Old tools, new tools and a more nuanced understanding of transmission dynamics.

Editor’s notes: By 2020, the Fast-Track strategy is aiming to reduce new HIV infections to 200 000 per year.  There is increasing recognition that if we are to succeed, we will need to do much more than simply putting people onto HIV treatment.  Despite the massive impact of ART on infectiousness, the decline in new infections at the community level is still not fast enough, even in countries like Botswana (see above) where 90-90-90 has almost been reached.  Renewed enthusiasm for primary prevention has also followed key trials of biomedical prevention tools including voluntary medical male circumcision and ARV-based prevention.  It is all too easy for us to forget the crucial role that condoms have played from the early days of the epidemic.  More recently, with HIV seen as a less terrifying infection, many programmes suffer from “condom fatigue”.  So it is good to see papers on the key importance of condoms as well as perspectives on how they are perceived by young men.

The magic of ARVs does not end with treatment.  We are finally moving to wider use of pre-exposure prophylaxis (PrEP).  There is no doubt that PrEP works when taken, but there are still plenty of questions for policy-makers about how to adopt it whole-heartedly into their national strategic plans and for financiers about how to pay for it.  Papers this month cover a range of experiences with PrEP from the US, where the huge majority of PrEP users still live, to Europe and Australia, where policies are finally moving towards wider use.  Long acting PrEP remains a key objective for many, as it might improve regular adherence, which has proved the Achilles’ heel of oral and topical PrEP in several of the large studies.

One of the ways to make PrEP most cost-effective is to ensure that it is available to people who are most likely to acquire HIV.  So the hope continues that phylogenetic analyses will allow more sophisticated understanding of the dynamics of the multiple overlapping networks of HIV transmission in communities.  Papers this month cover Australia and the PANGEA consortium of African research sites along with a cautionary comment about establishing the ethical framework for such studies, particularly among populations who are already subject to discrimination and criminalization.

When used correctly and consistently, condoms are highly effective not only to prevent HIV but also to prevent pregnancy and to prevent sexually transmitted infections.  Stover and colleagues have tried to capture all three benefits in one model.  They explore three potential scenarios for condom programming between now and 2030 in 81 countries that are priorities for family planning or HIV programmers or both.  The benefits of greater investment in condoms are huge.  In their most optimistic scenario, the authors suggest that if the entire gap between people who would like to use condoms and people who currently use them was filled (almost 11 billion condoms over the period), this could prevent up to 400 million unwanted pregnancies; 16.8 million new HIV infections and more than 700 million sexually transmitted infections.  The costs are quite modest, and at $115 per DALY averted this is an investment that everyone should support.  There are of course limitations in such a broad brush model, but it provides an excellent starting point.

The challenges in provision of condoms to young people go well beyond the cost and effectiveness considerations that underpin the previous analysis.  In an interesting qualitative study in South Africa, de Bruin and Panday-Soobrayan report their findings from focus group discussions with learners in 33 public schools.  Most of the learners were not in favour of provision of condoms at school, although they were keen on more youth friendly sexual and reproductive health and rights services within the public sector.  Many thought that provision of condoms would lead to earlier and more frequent sexual contacts, despite considerable experience showing that this is not the case in other settings.

Multiple trials have shown that PrEP is extremely effective when it is used consistently and correctly.  Many countries in all continents are now beginning to work out where it fits within their combination prevention package.  To date, the large majority of PrEP users are in the United States of America (USA), where more than 140 000 people have started.  It is much harder to measure how many are still taking it regularly.  Patel and colleagues analysed utilization at three months after the initial prescription of PrEP in three major PrEP clinics in three states in the USA.  18% of the 201 people (90% male) seen at baseline did not use their PrEP and this was strongly predicted by insurance status, with around a four-fold risk of dropping out among those who were not insured.  Although the numbers are small, this is an important study.  The authors suggest that increased insurance cover might make PrEP have a greater impact.  More broadly it raises the challenge that PrEP is often needed most by people least able to access it.  This will be a real challenge in countries where people most at risk, such as gay men and other men who have sex with men and sex workers, are criminalized or discriminated against in many health care settings.

In Australia, PrEP has been provided through large demonstration projects while awaiting decisions about how to include it in routine practice.  Lal and colleagues report results from 114 (one transgender woman, the rest male) people taking PrEP in the Victorian PrEP Demonstration project.  Participants have to pay an equivalent of an insurance co-payment, in order to make the situation more like the “real world”.  The participants were recruited because they were at high risk of HIV engaging in condomless anal sex with partners who were known to be living with HIV or of unknown status.  Adherence to PrEP was excellent as measured by a variety of reported and biological measures.  They observed one seroconversion in a man with exposure two weeks before starting PrEP who was already in the process of seroconverting and whose virus was found to be resistant to emtricitabine.  The only other seroconversion occurred in someone who had not yet started PrEP.  The authors found a substantial increase in rates of gonorrhoea and chlamydia once participants were “stable” on PrEP after three months.  There was also a significant reduction in condom use with both regular and casual partners.  This is one of the first studies to document important risk compensation among PrEP users.  Of course, preventing HIV is a huge benefit that generally outweighs the harms of additional treatment for sexually transmitted infections.  However, the study emphasizes the importance of enhancing sexual health services alongside PrEP and reminds us that people most at risk of HIV are also at high risk of other infections (and also of pregnancy in the context of heterosexual transmission.)  If PrEP is integrated within a broad sexual health service, there could be considerable synergistic benefits.

Gay men and men who have sex with men who enrolled in the PrEP demonstration project in Amsterdam also had high concomitant rates of hepatitis C virus (HCV).  Hoorenborg and colleagues found that around 5% of the 375 men enrolled in the project were co-infected.  The HCV found among these men were genetically similar to those circulating in the population of gay men and other men who have sex with men living with HIV, and more distinct from HCV from other risk groups.  This is good evidence that HCV and HIV both circulate in this population, and emphasizes once again the need for more integrated services, including hepatitis screening.

The ÉCLAIR study is a phase 2a trial of cabotegravir injections in healthy HIV-negative male volunteers.  As noted, adherence is a major challenge in many PrEP trials; although notably less of a problem when people choose to take PrEP in demonstration projects.  It is hoped that cabotegravir could be the first long acting PrEP.  Markowitz and colleagues presented the results of this study at CROI 2017.  The authors point out that although the injections are painful, many men stated that they would be happy to continue if the injections were effective.  No serious safety challenges emerged. The pharmacokinetics suggests that a dose given more frequently will be needed – and subsequent trials will use a two monthly regimen. 

One group for whom PrEP has been recommended by WHO for some years are serodiscordant couples (SDCs).  The Partners PrEP study, which forms one of the cornerstones for the evidence that PrEP works for both men and women, was conducted in SDCs.  The idea is to protect the HIV-negative partner from infection until such time as the partner living with HIV has been on ART consistently and suppressed their viral load.  So a study from the Centers for Disease Control USA is relevant to discussions of PrEP.  Crepaz and colleagues found that around 6000 new HIV infections occur each year in the USA among men and women having heterosexual sex and are aware that their partner is living with HIV.  They point out that viral suppression is achieved by only around 50% of heterosexuals living with HIV and that an additional proportion does not know their HIV status.  So the importance of HIV testing, and of focusing efforts on serodiscordant couples is clear.  Such efforts include both improving HIV treatment effectiveness, and providing a range of prevention choices including PrEP until viral suppression is achieved.

While the study above used traditional epidemiological surveillance reports, phylogenetics may provide additional insights into the dynamics of transmission.  In Australia, where notifications with HIV are rising steadily,  Castley and colleagues have examined the sequence data from almost 5000 viruses collected across the country from 2005-2012.  This sample is drawn from around 1200 new HIV infections per year (and around 27 000 people living with HIV).  The sample is not random, but reflects samples that were sent for sequencing to determine drug resistance.  Around one quarter of sequences are found in tight clusters (pairs, triplets or more) with other sequences, making it likely that they are closely connected by transmission.  Of course, all HIV sequences have been transmitted, so a longer time period and complete sampling would be expected to give a much higher proportion in clusters.  Indeed the more recent samples are around twice as likely to be in clusters as those collected at the start of the time period. Nonetheless, the large sample and the time period of collection allows some clear observations to be made.  In all states, the proportion of non-B subtypes is increasing, which must relate to travel and migration to and from Asia and Africa.  There is little evidence that the C subtypes (originally from Africa) are found in all male clusters suggesting little spill over into the community of gay men and other men having sex with men.  Larger clusters are more common among younger, all male networks. Like most molecular epidemiological studies, there are a small number of large clusters which represent highly active transmission.  These clusters are also most likely to be all male.  Taken together, the results suggest that the steady rise in notifications in Australia is probably due to increasing migration and travel and to ongoing active transmission networks among young gay men.  The challenge is to turn this sort of analysis into clear policy recommendations that can improve HIV prevention.

UNAIDS joined an interesting meeting on the ethics of phylogenetic studies in Africa organised by the PANGEA consortium.  Many of the issues discussed are also covered in a comment by Cohen on the importance of thinking through the risks inherent in these studies.  A key issue is to ensure that systems are reinforced to monitor any unexpected harms and to establish mitigation strategies to minimize them.  The challenges are not necessarily different to traditional epidemiological studies which may highlight networks and locations of groups that are criminalized or discriminated against.  In community consultations, prior to agreeing to go forward with phylogenetic studies, some potential participants even say that they would be keen to “know who infected them” in order to punish them.  This is clearly NOT the aim of such studies and emphasizes the importance of clear information about the limitations of the techniques which cannot usually rule out the possibility of additional links in the transmission chain.  Issues of anonymised information and what to do if clinically relevant results such as drug resistance mutations are uncovered as incidental findings also need to be discussed.

Furthermore, Ratmann and colleagues, reporting on the first 4000 sequences from the PANGEA consortium (largely from the Rakai project in Uganda), also emphasize some of the technical challenges that may lead to erroneous results in creating phylogenies.  There is little doubt that as the cost of sequencing falls and as the technologies and software become increasingly straightforward, we will see more and more studies of sequence data.  It is likely that analysis of these data will lead to more nuanced approaches to HIV prevention, particularly as the overall incidence falls, and sharper tools are needed to dissect the pathways of ongoing transmission.

The case for investing in the male condom

Stover J, Rosen JE, Carvalho MN, Korenromp EL, Friedman HS, Cogan M, Deperthes B. PLoS One. 2017 May 16;12(5):e0177108. doi: 10.1371/journal.pone.0177108. eCollection 2017.

When used correctly and consistently, the male condom offers triple protection from unintended pregnancy and the transmission of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). However, with health funding levels stagnant or falling, it is important to understand the cost and health impact associated with prevention technologies. This study is one of the first to attempt to quantify the cost and combined health impact of condom use, as a means to prevent unwanted pregnancy and to prevent transmission of STIs including HIV. This paper describes the analysis to make the case for investment in the male condom, including the cost, impact and cost-effectiveness by three scenarios (low in which 2015 condom use levels are maintained; medium in which condom use trends are used to predict condom use from 2016-2030; and high in which condom use is scaled up, as part of a package of contraceptives, to meet all unmet need for family planning by 2030 and to 90% for HIV and STI prevention by 2016) for 81 countries from 2015-2030. An annual gap between current and desired use of 10.9 billion condoms was identified (4.6 billion for family planning and 6.3 billion for HIV and STIs). Under a high scenario that completely reduces that gap between current and desired use of 10.9 billion condoms, we found that by 2030 countries could avert 240 million DALYs. The additional cost in the 81 countries through 2030 under the medium scenario is $1.9 billion, and $27.5 billion under the high scenario. Through 2030, the cost-effectiveness ratios are $304 per DALY averted for the medium and $115 per DALY averted for the high scenario. Under the three scenarios described above, our analysis demonstrates the cost-effectiveness of the male condom in preventing unintended pregnancy and HIV and STI new infections. Policy makers should increase budgets for condom programming to increase the health return on investment of scarce resources.

Abstract  Full-text [free] access

Learners' perspectives on the provision of condoms in South African public schools.

de Bruin WE, Panday-Soobrayan S. AIDS care. 2017 May 16:1-4. doi: 10.1080/09540121.2017.1327647. [Epub ahead of print]

A stubborn health challenge for learners in South African public schools concerns sexual and reproductive health and rights (SRHR). In 2015, the Department of Basic Education (DBE) proposed the provision of condoms and SRHR-services to learners in schools. This study aimed to contribute to the finalisation and implementation of DBE's policy by exploring learners' perspectives on the provision of condoms and SRHR-services in schools. Sixteen focus group discussions were conducted with learners (n = 116) from 33 public schools, to assess their attitudes, social influences, and needs and desires regarding condom provision and SRHR-services in schools. The majority of learners did not support condom provision in schools as they feared that it may increase sexual activity. Contrarily, they supported the provision of other SRHR-services as clinics fail to offer youth-friendly services. Learners' sexual behaviour and access to SRHR-services are strongly determined by their social environment, including traditional norms and values, and social-pressure from peers and adults. Learners' most pressing needs and desires to access condoms and SRHR-services in school concerned respect, privacy and confidentiality of such service provision. Implementation of DBE's policy must be preceded by an evidence-informed advocacy campaign to debunk myths about the risk of increased sexual activity, to advocate for why such services are needed, to shift societal norms towards open discussion of adolescent SRHR and to grapple with the juxtaposition of being legally empowered but socially inhibited to protect oneself from HIV, STIs and early pregnancy. Provision of condoms and other SRHR-services in schools must be sensitive to learners' privacy and confidentiality to minimise stigma and discrimination.

Abstract  Full-text [free] access

Impact of insurance coverage on utilization of pre-exposure prophylaxis for HIV prevention

Patel RR, Mena L, Nunn A, McBride T, Harrison LC, Oldenburg CE, Liu J, Mayer KH, Chan PA.  PLoS One. 2017 May 30;12(5):e0178737 . doi: 10.1371/journal.pone.0178737. eCollection 2017.

Pre-exposure prophylaxis (PrEP) can reduce U.S. HIV incidence. We assessed insurance coverage and its association with PrEP utilization. We reviewed patient data at three PrEP clinics (Jackson, Mississippi; St. Louis, Missouri; Providence, Rhode Island) from 2014-2015. The outcome, PrEP utilization, was defined as patient PrEP use at three months. Multivariable logistic regression was performed to determine the association between insurance coverage and PrEP utilization. Of 201 patients (Jackson: 34%; St. Louis: 28%; Providence: 28%), 91% were male, 51% were White, median age was 29 years, and 21% were uninsured; 82% of patients reported taking PrEP at three months. Insurance coverage was significantly associated with PrEP utilization. After adjusting for Medicaid-expansion and individual socio-demographics, insured patients were four times as likely to use PrEP services compared to the uninsured (OR: 4.49, 95% CI: 1.68-12.01; p = 0.003). Disparities in insurance coverage are important considerations in implementation programs and may impede PrEP utilization.

Abstract  Full-text [free] access

Medication adherence, condom use and sexually transmitted infections in Australian PrEP users: interim results from the Victorian PrEP demonstration project

Lal L, Audsley J, Murphy D, Fairley CK, Stoove M, Roth N, Moore R, Tee BK, Puratmaja N, Anderson PL, Leslie D, Grant RM, De Wit J, Wright E; VicPrEP Study Team. AIDS. 2017 May 1 doi: 10.1097/QAD.0000000000001519. [Epub ahead of print]

Objective: HIV Pre-exposure prophylaxis (PrEP) decreases risk of HIV acquisition however its efficacy is closely dependent on adherence. There is also concern that the preventive effect of PrEP may be offset by risk compensation, notably an increase in condomless anal sex.

Design: Multi-site, open-label demonstration study that recruited people at current or recent risk of HIV infection in Melbourne, Australia.

Methods: Participants were recruited from three general practice clinics and one sexual health clinic in Melbourne and consented to take daily tenofovir/emtricitabine for 30 months. Sexual practice data, HIV and sexually transmitted infection (STI) test results were collected at baseline and 3-monthly during follow up. PrEP adherence was evaluated by self-report at clinical visits, online surveys, refill-based assessments and dried blood spot (DBS) testing. We present a 12-month interim analysis.

Results: 114 people were recruited. We observed a significant decline in condom use which occurred concomitantly with a significant increase in STIs over the first 12 months of PrEP. Incidence (per 100PY) of any STI was 43.2 and 119.8 at m0-3 and M3-12, respectively (IRR 2.77 (1.52, 5.56)). Adherence to PrEP medication was high by all measures, including six month TDF-FTC levels in DBS.

Conclusions: We found significant reduction in condom use and an increase STIs over the first 12 months of follow-up. High medication adherence rates coupled with a decline in condom use and a rise in STIs, suggests that prevention, early detection and treatment of STIs is a chief research priority in the current era of HIV PrEP.

Abstract

Men who have sex with men starting pre-exposure prophylaxis (PrEP) are at risk of HCV infection: evidence from the Amsterdam PrEP study

Hoornenborg E, Achterbergh RC, Van Der Loeff MF, Davidovich U, Hogewoning A, de Vries HJ, Schinkel J, Prins M, Laar TJWV; Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative, MOSAIC study group. AIDS. 2017 May 1. doi: 10.1097/QAD.0000000000001522. [Epub ahead of print].

Objectives and Design: Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start pre-exposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM.

Methods: At enrolment in the Amsterdam PrEP (AMPrEP) demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis.

Results: Of 375 HIV-negative MSM enrolled in AMPrEP, 18 (4.8%, 95%CI 2.9%-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15/18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%) and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV.

Conclusion: HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.

Abstract

Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial.

Markowitz M, Frank I, Grant RM, Mayer KH, Elion R, Goldstein D, Fisher C, Sobieszczyk ME, Gallant JE, Van Tieu H, Weinberg W, . Margolis DA, Hudson KJ, Stancil BS, Ford SL, Patel P, Gould E, Rinehart AR, Smith KY, Spreen WR. Lancet HIV. 2017 May 22. pii: S2352-3018(17)30068-1. doi: 10.1016/S2352-3018(17)30068-1. [Epub ahead of print]

Background: Cabotegravir (GSK1265744) is an HIV-1 integrase strand transfer inhibitor with potent antiviral activity and a long half-life when administered by injection that prevented simian-HIV infection upon repeat intrarectal challenge in male macaques. We aimed to assess the safety, tolerability, and pharmacokinetics of long-acting cabotegravir injections in healthy men not at high risk of HIV-1 infection.

Methods: We did this multicentre, double-blind, randomised, placebo-controlled, phase 2a trial at ten sites in the USA. Healthy men (aged 18-65 years) deemed not at high risk of acquiring HIV-1 at screening were randomly assigned (5:1), via computer-generated central randomisation schedules, to receive cabotegravir or placebo. Participants received oral cabotegravir 30 mg tablets or matching placebo once daily during a 4 week oral lead-in phase, followed by a 1 week washout period and, after safety assessment, three intramuscular injections of long-acting cabotegravir 800 mg or saline placebo at 12 week intervals. Study site staff and participants were masked to treatment assignment from enrolment through week 41 (time of the last injection). The primary endpoint was safety and tolerability from the first injection (week 5) to 12 weeks after the last injection. We did analysis in the safety population, defined as all individuals enrolled in the study who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov identifier, NCT02076178.

Findings: Between March 27, 2014, and Feb 23, 2016, we randomly assigned 127 participants to receive cabotegravir (n=106) or placebo (n=21); 126 (99%) participants comprised the safety population. Most participants were men who have sex with men (MSM; n=106 [83%]) and white (n=71 [56%]). 87 (82%) participants in the cabotegravir group and 20 (95%) participants in the placebo group completed the injection phase. Adverse events (n=7 [7%]) and injection intolerability (n=4 [4%]) were the main reasons for withdrawal in the cabotegravir group. The frequency of grade 2 or higher adverse events was higher in participants in the long-acting cabotegravir group (n=75 [80%]) than in those in the placebo group (n=10 [48%]; p=0·0049), mostly due to injection-site pain (n=55 [59%]). No significant differences were noted in concomitant medications, laboratory abnormalities, electrocardiogram, and vital sign assessments. Geometric mean trough plasma concentrations were 0·302 μg/mL (95% CI 0·237-0·385), 0·331 μg/mL (0·253-0·435), and 0·387 μg/mL (0·296-0·505) for injections one, two, and three, respectively, indicating lower than predicted exposure. The geometric mean apparent terminal phase half-life estimated after the third injection was 40 days. Two (2%) MSM acquired HIV-1 infection, one in the placebo group during the injection phase and one in the cabotegravir group 24 weeks after the final injection when cabotegravir exposure was well below the protein-binding-adjusted 90% inhibitory concentration.

Interpretation: Despite high incidence of transient, mild-to-moderate injection-site reactions, long-acting cabotegravir was well tolerated with an acceptable safety profile. Pharmacokinetic data suggest that 800 mg administered every 12 weeks is a suboptimal regimen; alternative dosing strategies are being investigated. Our findings support further investigation of long-acting injectable cabotegravir as an alternative to orally administered pre-exposure prophylaxis regimens.

Abstract

Examination of HIV infection through heterosexual contact with partners who are known to be HIV infected in the United States, 2010-2015

Crepaz N, Dong B, Chen M, Hall I. AIDS. 2017 Jul 17;31(11):1641-1644. doi: 10.1097/QAD.0000000000001526.

Using data from the National HIV Surveillance System, we examined HIV infections diagnosed between 2010 and 2015 attributed to heterosexual contact with partners previously known to be HIV infected. More than four in 10 HIV infections among heterosexual males and five in 10 HIV infections among heterosexual women were attributed to this group. Findings may inform the prioritization of prevention and care efforts and resource allocation modeling for reducing new HIV infection among discordant partnerships.

Abstract

A national study of the molecular epidemiology of HIV-1 in Australia 2005–2012

Castley A, Sawleshwarkar S, Varma R, Herring B, Thapa K, Dwyer D, Chibo D, Nguyen N, Hawke K, Ratcliff R, Garsia R, Kelleher A, Nolan D; Australian Molecular Epidemiology Network-HIV (AMEN-HIV).. PLoS One. 2017 May 10;12(5):e0170601. doi: 10.1371/journal.pone.0170601. eCollection 2017.

Introduction: Rates of new HIV-1 diagnoses are increasing in Australia, with evidence of an increasing proportion of non-B HIV-1 subtypes reflecting a growing impact of migration and travel. The present study aims to define HIV-1 subtype diversity patterns and investigate possible HIV-1 transmission networks within Australia.

Methods: The Australian Molecular Epidemiology Network (AMEN) HIV collaborating sites in Western Australia, South Australia, Victoria, Queensland and western Sydney (New South Wales), provided baseline HIV-1 partial pol sequence, age and gender information for 4873 patients who had genotypes performed during 2005-2012. HIV-1 phylogenetic analyses utilised MEGA V6, with a stringent classification of transmission pairs or clusters (bootstrap ≥98%, genetic distance ≤1.5% from at least one other sequence in the cluster).

Results: HIV-1 subtype B represented 74.5% of the 4873 sequences (WA 59%, SA 68.4%, w-Syd 73.8%, Vic 75.6%, Qld 82.1%), with similar proportion of transmission pairs and clusters found in the B and non-B cohorts (23% vs 24.5% of sequences, p = 0.3). Significantly more subtype B clusters were comprised of ≥3 sequences compared with non-B clusters (45.0% vs 24.0%, p = 0.021) and significantly more subtype B pairs and clusters were male-only (88% compared to 53% CRF01_AE and 17% subtype C clusters). Factors associated with being in a cluster of any size included; being sequenced in a more recent time period (p<0.001), being younger (p<0.001), being male (p = 0.023) and having a B subtype (p = 0.02). Being in a larger cluster (>3) was associated with being sequenced in a more recent time period (p = 0.05) and being male (p = 0.008).

Conclusion: This nationwide HIV-1 study of 4873 patient sequences highlights the increased diversity of HIV-1 subtypes within the Australian epidemic, as well as differences in transmission networks associated with these HIV-1 subtypes. These findings provide epidemiological insights not readily available using standard surveillance methods and can inform the development of effective public health strategies in the current paradigm of HIV prevention in Australia

Abstract  Full-text [free] access

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

Ratmann O, Wymant C, Colijn C, Danaviah S, Essex M, Frost SD, Gall A, Gaiseitsiwe S, Grabowski M, Gray R, Guindon S, von Haeseler A, Kaleebu P, Kendall M, Kozlov A, Manasa J, Minh BQ, Moyo S, Novitsky V, Nsubuga R, Pillay S, Quinn TC, Serwadda D, Ssemwanga D, Stamatakis A, Trifinopoulos J, Wawer M, Leigh Brown A, de Oliveira T, Kellam P, Pillay D, Fraser C.. AIDS Res Hum Retroviruses. 2017 May 25. doi: 10.1089/AID.2017.0061. [Epub ahead of print].

To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3' end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

Abstract  Full-text [free] access

 

Africa, Asia, Europe, Northern America, Oceania
Afghanistan, Angola, Australia, Azerbaijan, Bangladesh, Benin, Bolivia, Botswana, Brazil, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Congo, Côte d'Ivoire, Democratic People's Republic of Korea, Democratic Republic of the Congo, Djibouti, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, Haiti, India, Indonesia, Iran (Islamic Republic of), Iraq, Jamaica, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, Niger, Nigeria, Pakistan, Papua New Guinea, Peru, Philippines, Russian Federation, Rwanda, Sao Tome and Principe, Senegal, Sierra Leone, Solomon Islands, Somalia, South Africa, South Sudan, Sudan, Swaziland, Tajikistan, Togo, Turkmenistan, Uganda, Ukraine, United Republic of Tanzania, United States of America, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
  • share
0 comments.

Key populations need so much more than HIV-specific services – involve them at every stage of planning and programming

Editor’s notes: This month sees a welcome set of papers covering female sex workers in West Africa; gay men and other men who have sex with men in the Middle East and in East Africa; people who inject drugs in the USA and eastern Europe.

Sex work is legal in Cote d’Ivoire although soliciting and pandering are criminalized, which creates legal barriers to practicing sex work.  Legalization does not necessarily prevent widespread abuse of power. Lyons and colleagues recruited 466 female sex workers in Abidjan through a respondent driven sampling approach.  A structured interview and rapid HIV test was performed.  Around 11% of the women were found to be living with HIV and it is clear that there are large unmet needs for HIV-specific services.  Only one quarter of those living with HIV reported that they knew their status and of these, only a few were already taking ART.  However, the focus of this study was on violence, both physical and sexual, which was alarmingly common, with around 54% of women reporting physical violence and 43% sexual violence.  The violence was most often perpetrated by spouses and boyfriends as well as by paying customers.  Other sex workers, pimps or managers and uniformed officers were also responsible for violence, both physical and sexual.  16% of women said that they had been tortured.  Collecting reliable data on sensitive areas with vulnerable populations is challenging.  The sampling method may introduce biases, and the interviews may lead to reported behaviours to “please” the interviewer.  However, this study included major efforts to work with the community of sex workers and their networks, and considerable trust has been built, so the results seem credible.  The authors call for structural interventions and policy reforms that have little to do with HIV directly, but would lead to an environment where HIV and other harms were greatly reduced.  There is also a direct need to ensure that sex workers have good access to HIV and other sexual and reproductive health services.

People who inject drugs also have many needs besides HIV services.  In the USA, the number of people who inject drugs is increasing.  This has led to a rising number of deaths from opioid overdose (around 30 000 in 2014), as well as increased HIV transmission, which makes the headlines of the news, when it occurs in settings where HIV is otherwise rare.  Cost-effective HIV prevention programmes for people who inject drugs are essential to the long-term health outcomes for this population and other high-risk groups in the USA.  Bernard and colleagues used a mathematical model and economic analysis to identify the most cost-effective interventions for HIV prevention programmes for people who inject drugs in the USA.

The authors found that under many likely assumptions about potential scale up, the best buy was always to provide opioid agonist therapy, which reduces injecting frequency and results in multiple, immediate quality-of-life improvements.  Needle and syringe exchange programmes are less expensive, but in these models produced fewer benefits, making them the next most cost-effective intervention, alone or in combination. PrEP was not likely to be cost-effective in this population except in the very highest risk settings.  This is in line with the values and preference expressed by many people who use drugs around the world.  The priority should be for “standard” harm reduction approaches, which will reduce HIV transmission, but have far wider benefits on the health and well-being of drug users and their communities.

Relatively little research is carried out with key populations in the Middle East.  Heimer and colleagues also used respondent driven sampling (with the same potential biases as above) to recruit 292 men who have sex with men in Beirut.  Although one quarter of the participants had been born in Syria and moved recently to Lebanon, the sampling method does reduce the precision of this estimate.  Of 36 people living with HIV identified, 32 were on HIV treatment, which is encouraging.  If the 32 on treatment were virally suppressed, the prevalence of “infectious HIV” in the survey was around 1.4%.  As we move forward into the viral load era, notions of risk for sexual behaviour will change, and we need to think about explicit descriptions such as “condomless sex” rather than simply referring to “unprotected sex”.  As stated above, the benefits of condoms for other sexually transmitted infections as well as for HIV need to be emphasized and the full range of ARV-based prevention made available in order to minimize the epidemic of HIV among gay men and other men who have sex with men in Lebanon and beyond.

The dynamics of the HIV epidemic in Ukraine are shifting.  Increasingly sexual transmission is becoming more common, and transmission through injecting drug use reducing.  Fearnhill and colleagues’ study of phylogenetics and recent infections among 876 newly diagnosed people living with HIV in Kiev highlights these trends.  The study also demonstrates plenty of uncertainty and suggests that the stigma associated with both injecting drug use and with gay men and other men having sex with men may lead to significant under-reporting of both in traditional epidemiological surveillance.  Although phylogenetics cannot prove misclassification, it is highly suggestive when large clusters of HIV from known gay men and other men who have sex with men include no women, but do include other men, who self-report to be heterosexual.  Transmission was most common among gay men and other men who have sex with men, and from those with recent infections.  HIV strains from women often cluster with those from people who inject drugs.  In a complex and dynamic environment with overlapping risk factors for HIV infection, phylogenetics adds a useful lens through which to examine what is happening.  Yet again, the challenge is to translate more granular understanding of the epidemics into clear public health policy and practice.

What do men who have sex with men in Kenya think about participating in HIV prevention research, such as a vaccine trial?  Doshi and colleagues used a social network-based approach to conduct in-depth interviews with 70 gay men and other men who have sex with men.  Here is what some of them said:

“He [the potential study participant] keeps hearing there is a research [study] that is starting, that there is money – one thousand or two, three thousand – he will run for the money…because it is someone’s life you have to be sure of what is going on…. You run for the better option because research comes in every type and researchers are everywhere in town.”

“Ok, you know most of the research coming to Kenya starts with MSM. Those are the ones that are tested on first so if there are side effects, those will be the first victims”

“It will benefit many of us…on my side…because sometimes I’m drunk I go out and meet people and they tell me they do not use condom…or… I’m drunk, I don’t know myself and I have already come to the bed with someone. Even I don’t know what he will do to me, if he will do me with a condom or if he will do me without a condom. Now the [HIV] vaccine…will be beneficial to me and the whole community”

This is a rich paper, giving insights into the reasons that people do or do not want to participate in vaccine trials.  It raises plenty of ethical questions about the balance between self-interest, altruism, coercion and consent.  It is encouraging that on the whole most participants saw the potential benefits to the wider community and would consider volunteering their time despite the associated risks.  Their perceptions were also coloured by previous research studies and how researchers had met their responsibilities for the care and well-being of their participants.  A good advertisement for the UNAIDS-AVAC Good Participatory Practice guidance!

Physical and sexual violence affecting female sex workers in Abidjan, Côte d'Ivoire: prevalence, and the relationship with the work environment, HIV, and access to health services

Lyons CE, Grosso A, Drame FM, Ketende S, Diouf D, Ba I, Shannon K, Ezouatchi R, Bamba A, Kouame A, Baral S. J Acquir Immune Defic Syndr. 2017 May 1;75(1):9-17. doi: 10.1097/QAI.0000000000001310.

Background: Violence is a human rights violation, and an important measure in understanding HIV among female sex workers (FSW). However, limited data exist regarding correlates of violence among FSW in Côte d'Ivoire. Characterizing prevalence and determinants of violence and the relationship with structural risks for HIV can inform development and implementation of comprehensive HIV prevention and treatment programs.

Methods: FSW > 18 years were recruited through respondent driven sampling (RDS) in Abidjan, Côte d'Ivoire. In total, 466 participants completed a socio-behavioral questionnaire and HIV testing. Prevalence estimates of violence were calculated using crude and RDS-adjusted estimates. Relationships between structural risk factors and violence were analyzed using χ2 tests and multivariable logistic regression.

Results: The prevalence of physical violence was 53.6% (250/466), and sexual violence was 43.2% (201/465) among FSW in this study. Police refusal of protection was associated with physical (adjusted Odds Ratio [aOR]: 2.8; 95% confidence interval [CI]: 1.7 to 4.4) and sexual violence (aOR: 3.0; 95% CI: 1.9 to 4.8). Blackmail was associated with physical (aOR: 2.5; 95% CI: 1.5 to 4.2) and sexual violence (aOR: 2.4; 95% CI: 1.5 to 4.0). Physical violence was associated with fear (aOR: 2.2; 95% CI: 1.3 to 3.1) and avoidance of seeking health services (aOR: 2.3; 95% CI: 1.5 to 3.8).

Conclusions: Violence is prevalent among FSW in Abidjan and associated with features of the work environment and access to care. These relationships highlight layers of rights violations affecting FSW, underscoring the need for structural interventions and policy reforms to improve work environments, and to address police harassment, stigma, and rights violations to reduce violence and improve access to HIV interventions.

Abstract

Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: a model-based analysis

Bernard CL, Owens DK, Goldhaber-Fiebert JD, Brandeau ML. PLoS Med. 2017 May 24;14(5):e1002312 doi: 10.1371/journal.pmed.1002312. eCollection 2017 May.

Background: The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID) a public health priority. Some of these programs have benefits beyond prevention of HIV-a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT), needle and syringe programs (NSPs), HIV testing and treatment (Test & Treat), and oral HIV pre-exposure prophylaxis (PrEP).

Methods and Findings: We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars), health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs) of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively) and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22 000 (95% CI: 5200, 46 000) infections and cost US$18 000 (95% CI: US$14 000, US$24 000) per QALY gained, 50% NSP coverage could avert up to 35 000 (95% CI: 8900, 43 000) infections and cost US$25 000 (95% CI: US$7000, US$76 000) per QALY gained, 50% Test & Treat coverage could avert up to 6700 (95% CI: 1200, 16 000) infections and cost US$27 000 (95% CI: US$15 000, US$48 000) per QALY gained, and 50% PrEP coverage could avert up to 37 000 (22 000, 58 000) infections and cost US$300 000 (95% CI: US$162 000, US$667 000) per QALY gained. When coverage expansions are allowed to include combined investment with other programs and are compared to the next best intervention, the model projects that scaling OAT coverage up to 50%, then scaling NSP coverage to 50%, then scaling Test & Treat coverage to 50% can be cost-effective, with each coverage expansion having the potential to cost less than US$50 000 per QALY gained relative to the next best portfolio. In probabilistic sensitivity analyses, 59% of portfolios prioritized the addition of OAT and 41% prioritized the addition of NSPs, while PrEP was not likely to be a priority nor a cost-effective addition. Our findings are intended to be illustrative, as data on achievable coverage are limited and, in practice, the expansion scenarios considered may exceed feasible levels. We assumed independence of interventions and constant returns to scale. Extensive sensitivity analyses allowed us to assess parameter sensitivity, but the use of a dynamic compartmental model limited the exploration of structural sensitivities.

Conclusions: We estimate that OAT, NSPs, and Test & Treat, implemented singly or in combination, have the potential to effectively and cost-effectively prevent HIV in US PWID. PrEP is not likely to be cost-effective in this population, based on the scenarios we evaluated. While local budgets or policy may constrain feasible coverage levels for the various interventions, our findings suggest that investments in combined prevention programs can substantially reduce HIV transmission and improve health outcomes among PWID.

Abstract  Full-text [free] access

HIV risk, prevalence, and access to care among men who have sex with men in Lebanon

Heimer R, Barbour R, Khoury D, Crawford FW, Shebl FM, Aaraj E, Khoshnood K. AIDS Res Hum Retroviruses. 2017 Jun 29 doi: 10.1089/AID.2016.0326. [Epub ahead of print].

Objective: Little is known about HIV prevalence and risk among men who have sex with men in much of the Middle East, including Lebanon. Recent national level surveillance has suggested an increase in HIV prevalence concentrated among men in Lebanon. We undertook a biobehavioral study to provide direct evidence for the spread of HIV.

Design: MSM were recruited by respondent driven sampling, interviewed, and offered HIV testing anonymously at sites located in Beirut, Lebanon from October 2014 through February 2015. The interview questionnaire was designed to obtain information on participants' sociodemographic situation, sexual behaviors, alcohol and drug use, health, HIV testing and care, experiences of stigma and discrimination. Individuals not reporting an HIV diagnosis were offered optional, anonymous HIV testing.

Results: Among the 292 MSM recruited, we identified 36 cases of HIV (12.3%). A quarter of the MSM were born in Syria and recently arrived in Lebanon. Condom use was uncommon; 65% reported unprotected sex with other men. Group sex encounters were reported by 22% of participants. Among the 32 individuals already aware of their infection, 30 were in treatment and receiving antiretroviral therapy.

Conclusions: HIV prevalence was substantially increased over past estimates. Efforts to control future increases will have to focus on reducing specific risk behaviors and experienced stigma and abuse, especially among Syrian refugees.

Abstract

A phylogenetic analysis of HIV-1 sequences in Kiev: findings among key populations

Fearnhill E, Gourlay A, Malyuta R, Simmons R, Ferns RB, Grant P, Nastouli E, Karnets I, Murphy G, Medoeva A, Kruglov Y, Yurchenko A, Porter K; CASCADE Collaboration in EuroCoord. Clin Infec Dis 2017 May 29: doi: 10.1093/cid/cix499. [Epub ahead of print].

Background: The HIV epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission.

Methods: Protease and RT sequences from 876 new HIV diagnoses (April 2013 - March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥ 2 sequences, ≥ 80% local branch support and maximum genetic distance of all sequence pairs in the cluster ≤ 2.5%. Recent infection was determined through the LAg avidity EIA assay. Sequences were analysed for transmitted drug resistance (TDR) mutations.

Results: 30% of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (OR 4.38 [95% CI 2.56-7.50]), risk group (OR 5.65 [3.27-9.75]) for men who have sex with men compared to heterosexual males, recent, compared to long-standing, infection (OR 2.72 [1.64-4.52]), reported sex work contact (OR 1.93 [1.07-3.47]) and younger age groups compared to age ≥36 (OR 1.83 [1.10-3.05] for age ≤25). Females were associated with lower odds of clustering than heterosexual males (OR 0.49 [0.31-0.77]). In multivariate analysis, risk group, subtype and age group were independently associated with clustering (p<0.001, p=0.007 and p=0.033). 18 sequences (2.1%) indicated evidence of TDR.

Conclusions: Our findings suggest high levels of transmission and bridging between risk groups.

Abstract  Full-text [free] access

Contextualizing willingness to participate: recommendations for engagement, recruitment & enrolment of Kenyan MSM in future HIV prevention trials

Doshi M, Avery L, Kaddu RP, Gichuhi M, Gakii G, du Plessis E, Dutta S, Khan S, Kimani J, Lorway RR. BMC Public Health. 2017 May 18;17(1):469 doi: 10.1186/s12889-017-4395-4.

Background: The HIV epidemic among men who have sex with men (MSM) continues to expand globally. The addition of an efficacious, prophylactic vaccine to combination prevention offers immense hope, particularly in low- and middle- income countries which bear the greatest global impact. However, in these settings, there is a paucity of vaccine preparedness studies that specifically pertain to MSM. Our study is the first vaccine preparedness study among MSM and female sex workers (FSWs) in Kenya. In this paper, we explore willingness of Kenyan MSM to participate in HIV vaccine efficacy trials. In addition to individual and socio-cultural motivators and barriers that influence willingness to participate (WTP), we explore the associations or linkages that participants draw between their experiences with or knowledge of medical research both generally and within the context of HIV/AIDS, their perceptions of a future HIV vaccine and their willingness to participate in HIV vaccine trials.

Methods: Using a social network-based approach, we employed snowball sampling to recruit MSM into the study from Kisumu, Mombasa, and Nairobi. A field team consisting of seven community researchers conducted in-depth interviews with a total of 70 study participants. A coding scheme for transcribed and translated data was developed and the data was then analysed thematically.

Results: Most participants felt that an HIV vaccine would bring a number of benefits to self, as well as to MSM communities, including quelling personal fears related to HIV acquisition and reducing/eliminating stigma and discrimination shouldered by their community. Willingness to participate in HIV vaccine efficacy trials was highly motivated by various forms of altruism. Specific researcher responsibilities centred on safe-guarding the rights and well-being of participants were also found to govern WTP, as were reflections on the acceptability of a future preventive HIV vaccine.

Conclusion: Strategies for engagement of communities and recruitment of trial volunteers for HIV vaccine efficacy trials should not only be grounded in and informed by investigations into individual and socio-cultural factors that impact WTP, but also by explorations of participants' existing experiences with or knowledge of medical research as well as attitudes and acceptance towards a future HIV vaccine.

Abstract  Full-text [free] access

 

Africa, Asia, Northern America
  • share
0 comments.

H*V – can we do better for HIV, HBV and HCV if we all work together?

Editor’s notes: The Sustainable Development Goals (SDGs) signal a major shift in the way that the United Nations and her development partners aim to shape the next decades.  Whereas the Millennium Development Goals reinforced specific programmes for HIV, tuberculosis and malaria, the SDGs call for a more integrated approach to health and well-being and encourage integration and synergy wherever it makes sense.  Hepatitis is one obvious area in which better collaboration and coordination could yield benefits.  Hepatitis B (HBV) and C (HCV) viruses are both more common in some of the populations most affected by HIV.  HCV can now be cured with drugs that derive directly from the HIV portfolio, while some ARVs have a direct effect on HBV.

Rwanda is one of the first countries in sub-Saharan Africa to set up a control programme for viral hepatitis, building on the infrastructure established for HIV. Umutesi and colleagues report on results of screening almost 120 000 people living with HIV who entered care for markers of HBV and HCV.  Around 5000 people (4.3%) were identified with a positive Hepatitis B surface antigen and a similar number (4.6%) were found to have antibodies against HCV.  There was marked variation geographically with a range by district from 2%-11% for HBV, higher in more urban areas and in men.  For HCV the range was from 3%-8% and was higher in more rural areas, and also in men.  This study provides a good platform to estimate numbers of people who might need treatment and to plan the next steps in an integrated programme.

People who inject drugs are particularly severely affected by HCV, and so co-infection with both HIV and HCV is common in areas where both viruses circulate.  Some estimates from Ho Chi Minh City in Viet Nam suggest that more than 40% of people who inject drugs are living with HIV and that essentially all of these people are also co-infected with HCV.  Birger R and colleagues developed a mathematical model to explore the likely impact of interventions aimed at HIV, HCV or broad harm reduction [with methadone maintenance treatment (MMT)] on future mortality and incidence of both infections.  While ART scale up reduces HIV incidence and mortality, it has no effect on HCV.  MMT is effective at reducing incidence of both HIV and HCV (and has morbidity and mortality benefits beyond these viruses).  However, MMT does not help the many people already living with HCV and so has little effect on HCV related mortality. So the model is clear that treatment for HCV needs to be an important part of a combined programme and that we urgently need to find ways to reduce the price of directly acting antivirals if we are to save more Vietnamese lives.

Haldane and colleagues have also focused on this intersection between HIV and substance use services.  They carried out a systematic review to understand the models and implications of integration of service delivery.  The authors expand their typology of integration models considering the point of entry of the client, and the degree to which services are co-located and delivered.  Integration can be considered as “clinical”, “service” or “systems”.  The first two can operate at the micro or meso level meaning that individual staff can deal with both situations, or that staff are trained to provide appropriate referrals.  Systems level integration operates at a macro level and implies that programmes for each service make collaborations and coordinate in ways that may affect staffing, funding and fragmentation of services. Although there are theoretical advantages to coordination and integration (as shown by the mathematical model above), there are few good empirical studies of integrated service delivery reported outside the USA.  The authors considered that most of the intervention studies had a risk of bias in the interpretation of their impact, although all demonstrated positive changes in outcomes.  Furthermore, almost all the studies focussed on integration at the clinic or individual provider level (meso or micro) rather than addressing the larger systemic challenges that we need to consider.  If we are to achieve the ideals laid out in the Sustainable Development Goals, we will need to overcome some of these systemic challenges, particularly for populations that are criminalized and marginalized by many of the public services.

Prevalence of hepatitis B and C infection in persons living with HIV enrolled in care in Rwanda.

Umutesi J, Simmons B, Makuza JD, Dushimiyimana D, Mbituyumuremyi A, Uwimana JM, Ford N, Mills EJ, Nsanzimana S. BMC Infect Dis. 2017 May 2;17(1):315. doi: 10.1186/s12879-017-2422-9.

Background: Hepatitis B (HBV) and C (HCV) are important causes of morbidity and mortality in people living with human immunodeficiency virus (HIV). The burden of these co-infections in sub-Saharan Africa is still unclear. We estimated the prevalence of the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCVAb) among HIV-infected individuals in Rwanda and identified factors associated with infection.

Methods: Between January 2016 and June 2016, we performed systematic screening for HBsAg and HCVAb among HIV-positive individuals enrolled at public and private HIV facilities across Rwanda. Results were analyzed to determine marker prevalence and variability by demographic factors.

Results: Overall, among 117 258 individuals tested, the prevalence of HBsAg and HCVAb was 4.3% (95% confidence interval [CI] (4.2-4.4) and 4.6% (95% CI 4.5-4.7) respectively; 182 (0.2%) HIV+ individuals were co-infected with HBsAg and HCVAb. Prevalence was higher in males (HBsAg, 5.4% [5.1-5.6] vs. 3.7% [3.5-3.8]; HCVAb, 5.0% [4.8-5.2] vs. 4.4% [4.3-4.6]) and increased with age; HCVAb prevalence was significantly higher in people aged ≥65 years (17.8% [16.4-19.2]). Prevalence varied geographically.

Conclusion: HBV and HCV co-infections are common among HIV-infected individuals in Rwanda. It is important that viral hepatitis prevention and treatment activities are scaled-up to control further transmission and reduce the burden in this population. Particular efforts should be made to conduct targeted screening of males and the older population. Further assessment is required to determine rates of HBV and HCV chronicity among HIV-infected individuals and identify effective strategies to link individuals to care and treatment.

Abstract  Full-text [free] access

The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling study on people who inject drugs in Ho Chi Minh City, Vietnam.

Birger RB, Le T, Kouyos RD, Grenfell BT, Hallett TB. PLoS One. 2017 May 11;12(5):e0177195. doi: 10.1371/journal.pone.0177195. eCollection 2017.

Background: Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection is a major global health problem especially among people who inject drugs (PWID), with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV.

Methods: We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography. Antiretroviral therapy (ART) and Methadone Maintenance Therapy (MMT) scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in 2026, after a variety of MMT scale-up scenarios, and projected forward 10 years.

Results: Our results indicate that scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up has an impact on incidence of both infections. HCV treatment roll-out has a measurable impact on reductions of deaths, increasing multifold the mortality reductions afforded by just ART/MMT scale-ups.

Conclusion: HCV treatment roll-out can have major and long-lasting effects on averting PWID deaths on top of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV interventions is critical in Vietnam.

Abstract  Full-text [free] access 

Integrating HIV and substance use services: a systematic review

Haldane V, Cervero-Liceras F, Chuah FL, Ong SE, Murphy G, Sigfrid L, Watt N, Balabanova D, Hogarth S, Maimaris W, Buse K, Piot P, McKee M, Perel P, Legido-Quigley H. Journal of the International AIDS Society. 2017 May 30;20(1).http://dx.doi.org/10.7448/IAS.20.1.21585.

Introduction: Substance use is an important risk factor for HIV, with both concentrated in certain vulnerable and marginalized populations. Although their management differs, there may be opportunities to integrate services for substance use and HIV. In this paper we systematically review evidence from studies that sought to integrate care for people living with HIV and substance use problems.

Methods: Studies were included if they evaluated service integration for substance use and HIV. We searched multiple databases from inception until October 2015. Articles were screened independently by two reviewers and assessed for risk of bias.

Results and discussion: 11 057 records were identified, with 7616 after removal of duplicates. After screening titles and abstracts, 51 met the inclusion criteria. Integration models were categorized by location (HIV, substance use and other facilities), level of integration from micro (integrated care delivered to individuals) to macro (system level integrations) and degree of integration from least (screening and counselling only) to most (care for HIV, substance use and/or other illnesses at the same facility). Most reported descriptive or cohort studies; in four randomized control trials integrated activities improved patient outcomes. There is potential for integrating services at all facility types, including mobile health services. While services offering screening only can achieve synergies, there are benefits from delivering integrated treatment for HIV and substance use, including ease of referral to other mental health and social services.

Conclusions: Our review used a wide range of databases and conference archives to increase representation of papers from low- and middle-income countries. Limitations include the overrepresentation of studies from the United States, and the descriptive nature of the majority of papers. The evidence reviewed shows that greater integration offers important benefits in both patient and service outcomes but further research and outcome reporting is needed to better understand innovative and holistic care models at the complex intersection of substance use and HIV services.

Abstract  Full-text [free] access

Africa, Asia, Europe, Northern America
  • share
0 comments.

Do people take more risks when they know they are “protected”?

Editor’s notes: Risk compensation is a phenomenon well known to behavioural scientists.  When car-drivers wear seat belts, they may drive faster because they feel safer.  Despite some evidence to the contrary, a commonly voiced concern about PrEP is that people who take it will take more risks with their sexual health.  So it is reassuring to see two studies that examine partnership dynamics and condom use among people on antiretroviral therapy (ART) and among men who have been circumcised.

McGrath and Grapsa studied relationships and reported sexual behaviour among 632 people living with HIV and enrolled in an ongoing cohort study in KwaZulu Natal during the period, when only those with lower CD4 counts were eligible for ART.  They interviewed participants every 6 months, in person or by phone, for up to 36 months. This was in order to follow which relationships were formed and which dissolved and to determine how often participants were having sex and how often they were having condomless sex.  The authors clearly document (perhaps unsurprisingly) that many relationships dissolved (192 out of 565 partnerships at some time in the study) or formed (161 out of 132 individuals who were single at some time in the study).  Partnerships dissolved more frequently among people who had only been in a relationship for less than a year; people who drank alcohol and in partnerships where the participant described the relationship as being of “poor quality”.  New partners were more common for people who were younger; had not disclosed their HIV status; drank alcohol or reported having more than 3 lifetime sexual partners at the start of the study.  There was no suggestion that being on ART affected the likelihood of forming or leaving a partnership. This is important for mathematical models of HIV transmission in the era of universal treatment policies.

Sex was more frequently reported in people in more recent partnerships; people who knew their partners’ HIV status and among people who wanted more children.  Sex was less frequent and more often protected by a condom among people who did not trust their partner’s fidelity or where the couple did not live together.  People who were eligible for ART tended to use condoms more regularly during the follow up than people who were still “waiting for treatment”.  Other factors associated with more condom use included more equitable gender norms; HIV status disclosure and not living together.  Condoms were used less often in partnerships that included alcohol, partner violence or where the couple wanted more children.  Overall, the authors estimated that around 5.5% of sex acts were “risky” (that is unprotected with a partner who was HIV negative or where the HIV status was unknown) among those eligible for ART and around 13.2% for those not yet eligible.  Around one third of the participants reported having condomless sex at least once, but in almost half of these, they knew that their partner was also living with HIV.

Taking effective ART regularly means that people living with HIV are no longer infectious once their viral load is reliably suppressed.  However, it is clear that not everyone achieves viral load suppression.  This study provides useful prospective information about partnerships and sexual behaviour in the context of very high HIV transmission.  It is reassuring in showing that on the whole, sexual behaviour seems less risky, even before taking the huge effect of ART into account.  There was no evidence to suggest that risk compensation occurred in those offered ART.

In order to maximize the preventive benefits of ART, it is essential that people are supported to take their medicines regularly.  In crowded urban facilities in high prevalence settings, long waiting times, and challenges in stock management mean that people living with HIV have to be quite determined to negotiate the systems and minimize treatment interruptions.  Although it is national policy in Zambia and some other highly burden countries to provide three-month supplies to people whose HIV is stable and well controlled, McCarthy and colleagues found that less than half of people who should be getting three-month refills were doing so.  They instituted a cluster randomized trial of a quality improvement programme across 16 health facilities in Lusaka.  Each clinic follows around 4-5000 people on ART of whom around 1000 are stable and eligible for three-monthly refills.  The key element was for a focal point in each of the eight intervention clinics to be designated as a quality improvement officer and to be supported with materials to plan and monitor drug stocks and support local changes.  This is to ensure that stable patients did not have to spend long periods in the clinic or go away with less medicine than they needed.  The District Health Management team supported the quality improvement officers when the challenges identified were beyond their responsibilities or capabilities to change.  The programme led to a statistically significant 15% increase in the proportion of appropriate people receiving three-month refills (reaching 69%).  On average the intervention clinics became less congested (35 fewer visits per day compared to the controls) and had shorter waiting times (20 minutes shorter per visit) although these results did not reach statistical significance.

Another study exploring risk compensation was carried out by Shi and colleagues.  The authors used data from recent demographic and health surveys from countries that are part of the scale-up of voluntary medical male circumcision in East and Southern Africa.  Circumcision was most prevalent in Kenya (88% and 94% before and after 2008, when scale-up was pushed) and lowest in Zimbabwe (12% and 11% respectively). Overall condom usage increased in both circumcised and uncircumcised men.  Reports of condom use at last sex averaged around 15-16% before 2008 across the ten countries surveyed and rose to around 21% after 2008.  There was no suggestion that men who were circumcised were any less likely to use a condom than men who were not.  Similarly, there was no suggestion that circumcised men were more likely to have non-cohabiting partners.

The study also highlights big differences between countries, and between different groups.  Even among men with no regular partner, the use of a condom at last sex is often less than 50% with differences as expected also seen by age, education, religion and residence.  Promoting circumcision remains a hugely cost-effective approach to HIV prevention.  This study therefore provides important reassurance that the possibility of risk compensation is not serious for circumcision programmes.  Nonetheless we still have plenty of work to do to reach our targets and prevent HIV.

Does ART change partnership dynamics and HIV risk behaviours among PLWH? A cohort study in KwaZulu-Natal, South Africa.

McGrath N, Grapsa E. AIDS. 2017 Apr 10. doi: 10.1097/QAD.0000000000001502. [Epub ahead of print]

Objective: We explore the impact of antiretroviral therapy (ART) on partnership acquisition and dissolution rates and changes in sexual behaviours among HIV-infected adults.

Design: Using detailed longitudinal data from a prospective cohort of HIV-infected adults with CD4<200 cell/ml (ART-eligible) or CD4>500 cell/ml (pre-ART) conducted in rural KwaZulu-Natal, South Africa, 2009-2012.

Methods: Partnership acquisition and dissolution are explored through survival analysis methods, while generalized linear models were fitted for the sexual behaviour outcomes with interaction terms to allow the association with ART to vary over time. Throughout, the primary comparison of interest for each outcome is differences between the two ART groups.

Results: ART is not associated with partner acquisition or relationship dissolution. During follow-up, the two ART groups do not differ in the odds of being sexually active nor the number of sex acts, while the odds of unprotected sex are significantly lower for partnerships of ART-eligible participants, a0R = 0.26, 95%CI(0.15,0.43). Relationship-level characteristics including cohabitation status and wanting more children with that partner are associated with higher odds and increased frequency of sexual activity, increased odds of unprotected sex; while living with partner, higher relationship quality and longer relationship duration are associated with lower risk of partnership dissolution.

Conclusion: Being on ART was not associated with increased sexual risk behaviours, a reassuring finding given the WHO recommends ART initiation upon HIV diagnosis. The importance of relationship-level characteristics provides evidence that HIV care services should offer routine support for HIV disclosure and sexual risk reduction, and promotion of couples-testing and positive couple-relationships.

Abstract access 

Quality improvement intervention to increase adherence to ART prescription policy at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial.

McCarthy EA, Subramaniam HL, Prust ML, Prescott MR, Mpasela F, Mwango A, Namonje L, Moyo C, Chibuye B, van den Broek JW, Hehman L, Moberley S. PLoS One. 2017 Apr 18;12(4):e0175534. doi: 10.1371/journal.pone.0175534. eCollection 2017.

Introduction: In urban areas, crowded HIV treatment facilities with long patient wait times can deter patients from attending their clinical appointments and picking up their medications, ultimately disrupting patient care and compromising patient retention and adherence.

Methods: Formative research at eight facilities in Lusaka revealed that only 46% of stable HIV treatment patients were receiving a three-month refill supply of antiretroviral drugs, despite it being national policy for stable adult patients. We designed a quality improvement intervention to improve the operationalization of this policy. We conducted a cluster-randomized controlled trial in sixteen facilities in Lusaka with the primary objective of examining the intervention's impact on the proportion of stable patients receiving three-month refills. The secondary objective was examining whether the quality improvement intervention reduced facility congestion measured through two proxy indicators: daily volume of clinic visits and average clinic wait times for services.

Results: The mean change in the proportion of three-month refills among control facilities from baseline to endline was 10% (from 38% to 48%), compared to a 25% mean change (an increase from 44% to 69%) among intervention facilities. This represents a significant 15% mean difference (95% CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three-month refills. On average, control facilities had 15 more visits per day in the endline than in the baseline, while intervention facilities had 20 fewer visits per day in endline than in baseline, a mean difference of 35 fewer visits per day (P = 0.1). The change in the mean facility total wait time for intervention facilities dropped 19 minutes between baseline and endline when compared to control facilities (95% CI: -10.2-48.5; P = 0.2).

Conclusion: A more patient-centred service delivery schedule of three-month prescription refills for stable patients is viable. We encourage the expansion of this sustainable intervention in Zambia's urban clinics.

Abstract Full-text [free] access

Evidence that promotion of male circumcision did not lead to sexual risk compensation in prioritized sub-Saharan countries.

Shi CF, Li M, Dushoff J. PLoS One. 2017 Apr 25;12(4):e0175928. doi: 10.1371/journal.pone.0175928. eCollection 2017.

Background: WHO and UNAIDS prioritized 14 eastern and southern African countries with high HIV and low male circumcision prevalence for a voluntary medical male circumcision (VMMC) scale-up in 2007. Because circumcision provides only partial protection against HIV infection to men, the issue of possible risk compensation in response to VMMC campaigns is of particular concern. In this study, we looked at population-level survey data from the countries prioritized by WHO for a VMMC scale-up. We compared the difference in sexual risk behaviours (SRB) between circumcised and uncircumcised men before and after the WHO's official VMMC promotion.

Materials and Methods: Ten countries (Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe) participating in the WHO's VMMC scale-up had available data from the Demographic and Health Surveys (DHS). We used cumulative-link mixed models to investigate interactions between survey period and circumcision status in predicting SRB, in order to evaluate whether the difference between the behavior of the two groups changed before and after the scale-up, while controlling for socio-demographic and knowledge-related covariates. The main responses were condom use at last sex and number of non-cohabiting sexual partners, both in the last 12 months.

Results: There was little change in condom use by circumcised men relative to uncircumcised men from before the VMMC scale up to after the scale up. The relative odds ratio is 1.06 (95% CI, 0.95-1.18; interaction P = 0.310). Similarly, there was little change in the number of non-cohabiting partners in circumcised men (relative to uncircumcised men): the relative odds ratio of increasing the number of partners is 0.95 (95% CI, 0.86-1.05; interaction P = 0.319). Age, religion, education, job, marital status, media use and HIV knowledge also showed statistically significant association with the studied risk behaviours. We also found significant differences among countries, while controlling for covariates.

Conclusions: Overall, we find no evidence of sexual risk compensation in response to VMMC campaigns in countries prioritized by WHO. Changes in relative partner behaviour and the relative odds of condom use were small (and of uncertain sign). In fact, our estimates, though not significant, both suggest slightly less risky behavior. We conclude that sexual risk compensation in response to VMMC campaigns has not been a serious problem to date, but urge continued attention to local context, and to promulgating accurate messages about circumcision within and beyond the VMMC context.

Abstract   Full-text [free] access 

Africa
  • share
0 comments.

Do people living with HIV live well with HIV in the era of antiretroviral therapy?

Editor’s notes: As treatment for HIV becomes increasingly widespread, and HIV-related deaths continue to decline, more and more attention is being paid to chronic non-communicable diseases and to the overall quality of life of people living with HIV.  However, despite 71% of people living with HIV in sub-Saharan Africa there is little research on the impact of illness and treatment on quality of life in the region.

Nyongesa and colleagues provide a fascinating mixed methods study, nested within a larger study of children and adolescents with HIV, which begins to formulate and validate a culturally appropriate tool to measure quality of life in the Swahili speaking population of coastal Kenya.  They used the functional assessment of HIV infection (FAHI) questionnaire as the starting point.  This is an HIV specific adaptation of a tool initially used among people with cancer and widely validated and studied in European and US based populations. 47 questions are used to assess HIV-specific quality of life in five domains: physical; emotional; functional and global well being; social; and cognitive functioning.

Following a scoping literature review, the authors used qualitative interviews with 38 participants living with HIV (largely female [27]) to explore their perceptions of the impact of HIV in the day-to-day life of people living with HIV in general. The issues raised overlapped with all the domains of FAHI except cognitive functioning, which the authors suggest is perhaps under-recognized when there are many competing stressors on people’s lives.  The participants then answered a draft version of the FAHI, which had been translated, back translated and reviewed in a group to ensure comprehension and relevance.  Following adaptation, the FAHI Swahili version was then administered to a sample of 103 randomly selected study participants living with HIV and on antiretroviral therapy from the same study site.  The sample was almost entirely female (94%) reflecting their availability at the parent study centre, which focussed on children and adolescents living with HIV.  Overall, the authors conclude that the new adaptation of the tool seems appropriate for further research studies on quality of life among people living with HIV on treatment in East Africa.  While the study provides a great example of a serious approach to develop, standardize and validate a culturally appropriate tool, the qualitative results also provide considerable insight into the many ways in which HIV affects these Kenyan’s lives beyond the purely medical.  Well worth reading the open access paper.

A study in Europe focussed specifically on the health-related domain of quality of life in Amsterdam.  Langebeek and colleagues used two tools that are well validated in European settings to assess physical and mental health related quality of life in 541 individuals living with HIV and 526 control participants without HIV.  HIV infection was clearly associated with worse quality of life, both mental and physical despite most participants being well controlled on ART.  As we might expect,  people who had multiple co-morbidities were less likely to have a good quality of life regardless of HIV status, but HIV remained an independent predictor of poor quality of life.  For mental health, HIV and younger age were both independently associated with less good quality of life.  The clear message is that we need to look beyond antiretroviral therapy and provide good holistic care including both mental and physical health services for people living with HIV, particularly as the population gets older.

A related study from Gonciulea and colleagues shows that among older men living with HIV, there is a significant increase in the risk of osteoporosis related fractures.  Bone demineralization is known to occur with risk factors such as age, sex, and low body mass index (BMI).However, increasingly studies are showing that HIV-related factors, such as antiretroviral medicines, ongoing viral replication and ongoing inflammation, are also potential risk factors. The authors used the multicenter AIDS cohort study to compare fracture incidence rates among 1221 men living with HIV and 1408 HIV-negative men.  Both cohorts were aged over 40 years.  As expected, fractures occurred more commonly as people got older, but the people living with HIV developed more fractures at an earlier age.  This study therefore reinforces the previous one, with the possibility to offer osteoporosis screening to men over the age of 50 who are living with HIV.

Petraglia and colleagues also explored the challenge of osteoporosis in people living with HIV.  Chronic obstructive pulmonary disease is known to be associated with low bone mineral density (BMD) and greater fracture risk in HIV negative smokers. In fact the finding of emphysema alone on CT imaging is a strong, independent predictor of osteoporosis in this group. We are beginning to observe obstructive lung disease as a common comorbidity in people living with HIV and emphysema has been shown to occur at an earlier age with less tobacco exposure in HIV positive smokers.  The authors therefore aimed to determine whether CT scans alone could predict who would turn out to have osteoporosis among people living with HIV.  As expected, they found that, among 164 people living with HIV, age; smoking and emphysema on CT scan were all associated with reduced BMD in the thoracic spine (estimated from the CT scan).  However, they also found that the emphysematous changes were an independent marker for this measure of osteoporosis regardless of age, sex, smoking, and use of antiretroviral medicines or steroids.  If a CT scan or lung function test suggests obstructive airways disease or emphysema, we should have a higher index of suspicion for osteoporosis among people living with HIV.

A mixed methods approach to adapting and evaluating the functional assessment of HIV infection (FAHI), Swahili version, for use with low literacy populations.

Nyongesa MK, Sigilai A, Hassan AS, Thoya J, Odhiambo R, Van de Vijver FJ, Newton CR, Abubakar A. PLoS One. 2017 Apr 5;12(4):e0175021. doi: 10.1371/journal.pone.0175021. eCollection 2017.

Background: Despite bearing the largest HIV-related burden, little is known of the Health-Related Quality of Life (HRQoL) among people living with HIV in sub-Saharan Africa. One of the factors contributing to this gap in knowledge is the lack of culturally adapted and validated measures of HRQoL that are relevant for this setting.

Aims: We set out to adapt the Functional Assessment of HIV Infection (FAHI) Questionnaire, an HIV-specific measure of HRQoL, and evaluate its internal consistency and validity.

Methods: The three phase mixed-methods study took place in a rural setting at the Kenyan Coast. Phase one involved a scoping review to describe the evidence base of the reliability and validity of FAHI as well as the geographical contexts in which it has been administered. Phase two involved in-depth interviews (n = 38) to explore the content validity, and initial piloting for face validation of the adapted FAHI. Phase three was quantitative (n = 103) and evaluated the internal consistency, convergent and construct validities of the adapted interviewer-administered questionnaire.

Results: In the first phase of the study, we identified 16 studies that have used the FAHI. Most (82%) were conducted in North America. Only seven (44%) of the reviewed studies reported on the psychometric properties of the FAHI. In the second phase, most of the participants (37 out of 38) reported satisfaction with word clarity and content coverage whereas 34 (89%) reported satisfaction with relevance of the items, confirming the face validity of the adapted questionnaire during initial piloting. Our participants indicated that HIV impacted on their physical, functional, emotional, and social wellbeing. Their responses overlapped with items in four of the five subscales of the FAHI Questionnaire establishing its content validity. In the third phase, the internal consistency of the scale was found to be satisfactory with subscale Cronbach's α ranging from 0.55 to 0.78. The construct and convergent validity of the tool were supported by acceptable factor loadings for most of the items on the respective sub-scales and confirmation of expected significant correlations of the FAHI subscale scores with scores of a measure of common mental disorders.

Conclusion: The adapted interviewer-administered Swahili version of FAHI questionnaire showed initial strong evidence of good psychometric properties with satisfactory internal consistency and acceptable validity (content, face, and convergent validity). It gives impetus for further validation work, especially construct validity, in similar settings before it can be used for research and clinical purposes in the entire East African region.

Abstract Full-text [free] access 

Impact of co-morbidity and aging on health-related quality of life in HIV-positive and HIV-negative individuals.

Langebeek N, Kooij KW, Wit FW, Stolte IG, Sprangers MAG, Reiss P, Nieuwkerk PT; AGEhIV Cohort Study Group. AIDS. 2017 Apr 19. doi: 10.1097/QAD.0000000000001511. [Epub ahead of print].

Background: HIV-infected individuals may be at risk for the premature onset of age-associated non-communicable co-morbidities. Being HIV-positive, having comorbidities and being of higher age may adversely impact health-related quality of life (HRQL). We investigated the possible contribution of HIV infection, co-morbidities, and age on HRQL and depression.

Methods: HIV-infected individuals and uninfected controls from the AGEhIV Cohort Study were screened for the presence of co-morbidities. They completed the Short Form 36-item Health Survey to assess HRQL and the nine-item Patient Health Questionnaire to assess depression. Linear and logistic regression were used to investigate to which extent co-morbidities, aging and HIV infection were independently associated with HRQL and depression.

Results: HIV-infected individuals (n = 541) reported significantly worse physical and mental HRQL and had a higher prevalence of depression than HIV-uninfected individuals (n = 526). A higher number of co-morbidities and HIV-positive status were each independently associated with worse physical HRQL, whereas HIV-positive status and younger age were independently associated with worse mental HRQL and more depression. The difference in physical HRQL between HIV-positive and HIV-negative individuals did not become greater with a higher number of co-morbidities or with higher age.

Conclusions: In a cohort of largely well-suppressed HIV-positive participants and HIV-negative controls, HIV-positive status was significantly and independently associated with worse physical and mental HRQL and with an increased likelihood of depression. Our finding that a higher number of co-morbidities was independently associated with worse physical HRQL reinforces the importance to optimize prevention and management of co-morbidities as the HIV-infected population continues to age.

Abstract access 

 An increased rate of fracture occurs a decade earlier in HIV+ compared to HIV- men in the Multicenter AIDS Cohort Study (MACS).

Gonciulea A, Wang R, Althoff KN, Palella FJ, Lake J, Kingsley LA, Brown TT. AIDS. 2017 Apr 3. doi: 10.1097/QAD.0000000000001493 [Epub ahead of print].

Objectives: To determine the incidence and age-related fracture risk among HIV-infected (HIV+) and uninfected men (HIV-). To evaluate factors independently associated with fracture risk.

Design: Prospective, multicenter cohort study of men with or at risk for HIV.

Methods: Outcome measures: 1) all fractures (excluding skull, face, digits) and 2) fragility fractures (vertebral column, femur, wrist, humerus) were collected semiannually in 1221 HIV+ and 1408 HIV- men ≥ age 40. Adjusted incident rate ratios (aIRR) with an interaction term for age (40-49, 50-59, ≥60 years) and HIV serostatus were estimated with Poisson regression models accounting for additional risk factors.

Results: Fracture incidence increased with age among both HIV+ and HIV- men. While there was no significant difference in fracture incidence by HIV serostatus among men aged 40-49 years, the HIV+ men aged 50-59 years had a significantly higher incidence of all fractures (aIRR = 2.06 [1.49, 2.84]) and fragility fractures (aIRR = 2.06 [1.21, 3.50]) compared with HIV- participants of similar age. HIV modified the effect of age on all fractures (p = 0.002) but did not significantly modify the effect for fragility fractures (p = 0.135). Hypertension increased the rate of all fractures by 32% after adjustment for covariates (aIRR = 1.32 [1.04, 1.69]).

Conclusions: Fracture incidence increased with age among HIV+ and HIV- men but was higher among HIV+ men. A significant increase in fracture incidence was found among 50-59-year-old HIV+ men, highlighting the importance of osteoporosis screening for HIV infected men above the age of 50.

Abstract access 

Emphysema is associated with thoracic vertebral bone attenuation on chest CT scan in HIV-infected individuals.

Petraglia A, Leader JK, Gingo M, Fitzpatrick M, Ries J, Kessinger C, Lucht L, Camp D, Morris A, Bon J. PLoS One. 2017 Apr 27;12(4):e0176719. doi: 10.1371/journal.pone.0176719. eCollection 2017.

Background: Age-related chronic diseases are prevalent in HIV-infected persons in the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and emphysema have separately been shown to occur at a younger age and with lesser risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV infected smokers, emphysema has been shown to independently predict low BMD. We hypothesized that emphysema would independently associate with thoracic vertebral bone attenuation, a surrogate for bone mineral density, in HIV-infected individuals.

Methods: Clinical, pulmonary function, and radiographic data were analyzed for 164 individuals from the University of Pittsburgh's HIV Lung Research Center cohort. Chest CT scans were used to quantify emphysema and compute Hounsfield Unit (HU) attenuation of the 4th, 7th, and 10th thoracic vertebrae. The association between mean HU attenuation values across the three vertebrae and radiographic emphysema, age, sex, body mass index (BMI), steroid use, viral load, CD4 count, and forced expiratory volume in the first second (FEV1) was assessed by univariate and multivariate analyses.

Results: In univariate analysis, mean HU attenuation decreased with increasing age (p<0.001), pack years (p = 0.047), and percent emphysema (p<0.001). In a multivariable model, including pack years, age, sex, ART and steroid use, greater emphysema was independently associated with this surrogate marker of BMD in HIV-infected individuals (p = 0.034).

Conclusions: The association of emphysema with thoracic bone attenuation in HIV-infected individuals is consistent with previous reports in non-HIV infected smokers. These findings suggest that emphysema should be considered a potential marker of osteoporosis risk in HIV-infected individuals.

Abstract Full-text [free] access 

Africa, Europe, Northern America
  • share
0 comments.

Increasing HIV testing by sharing the load and updating tasks and traditions for traditional birth attendants and lay providers

Editor’s notes: Nigeria still has the highest number of new HIV infections among children in the world, around 40 000 annually, with the large majority arising from mother to child transmission.  In Nigeria, less than 20% of pregnant women receive HIV testing. This is due to several issues which include a limited number of HIV testing service delivery points and a limited number of deliveries taking place at health facilities.  Around two thirds of deliveries take place at home, traditionally supported by traditional birth attendants (TBAs).  Many TBAs in Nigeria have little knowledge of either the benefits or practice of HIV testing, nor of ways to reduce transmission of HIV to infants.

Chizoba and colleagues have developed and tested a model of antenatal care that aims to integrate TBAs within the government primary health care (PHC) network.  The intervention consisted of PHC clinics identifying a few TBAs who operated in the catchment area of the clinic. Between one and five of these TBAs was invited to the PHC clinic for a one-day training on HIV point of care testing, and asked to refer all women found to be positive to the clinic for confirmation and follow up.  Once a month TBAs came to the clinic for encouragement and to provide data on tests performed.  Once a quarter, the clinic visited the TBAs to provide supervision, mentoring and quality improvement training.  The TBAs were also paid $2 for every pregnant woman whom they tested for HIV, in order to compensate them for any loss of earnings from pregnant women living with HIV who would now be seen in the clinic rather than delivering at home. 

The authors used a quasi-experimental design for this study. Out of the 74 PEPFAR supported PHC clinics that provided HIV services in their antenatal clinics in Ebonyi state of Nigeria, 34 were interested in this new integrated approach, whereas 40 expressed no interest.  20 clinics were chosen at random from each of these categories, to avoid additional selection bias.  (Although as the authors state, there may already be considerable differences between the clinics that were interested and clinics that were not).  Comparisons were made before and after the programme was put in place, and also between clinics in the intervention group and those in the group that had not been interested to integrate services with the TBAs.

Despite this non-randomized design, the results are quite striking with more than twice as many women receiving HIV testing in the intervention clinics in the six months after the intervention began (going up from 2501 to 5346 across the 20 clinics).  There was no such increase in the non-intervention areas (which saw a change from 1770 to 1892 across the 20 clinics).  Furthermore the large majority of the increase was among women who had been tested by the TBAs. 

While this is hugely encouraging and a big increase, it will be important to see if the increase can be sustained as it is a significant change in the way that the TBAs and the PHC clinic staff work.  It is also not clear how much the increase is a result of the integration model and how much it relates to the additional payment that TBAs receive, which seems to amount to around $100 per TBA over the 6 month period of the assessment.

A thorough review of the role of trained lay providers in performing HIV tests was carried out as part of the WHO process that led to the guidance in 2015 that “Lay providers who are trained and supervised to use rapid diagnostic tests (RDTs) can independently conduct safe and effective HIV testing services.” Kennedy and colleagues now present the details of that systematic review.

Many national policies, particularly in African countries allow for HIV testing by trained lay providers using rapid diagnostic tests (RDTs) and even more allow lay providers to perform pre- and post-test counselling (around 80% of African countries in one survey of policies).  However, some countries limit these roles to trained healthcare providers due to concerns about lay providers’ ability to perform the tests accurately and reliably and to deliver high quality pre- and post-test counselling, linkage to appropriate prevention and clinical care services, and coordination with laboratory services to ensure the delivery of correct test results.

Despite widespread use of lay providers, there are actually rather few studies that directly compare the outcomes of testing between lay and professional providers.  The authors reviewed over 6000 titles, abstracts or full articles and found only five that allowed a direct comparison, while an additional six studies allowed the values and preferences of clients and providers to be assessed.

While this evidence base is very limited, findings from the single randomized trial (in the US) and one observational study (in Malawi), that compared pre- and post-intervention time periods, suggest that using trained lay providers can increase HIV testing uptake.  Three studies compared the quality of testing between lay providers and professional providers and found that both can achieve similar testing quality. Unfortunately, no studies measured adverse events following testing, nor linkage to care. The six values and preferences studies, also found support for lay providers.

This is the key evidence that underpins the strong recommendation from WHO and now also from many national authorities, that trained lay providers are an essential component in the efforts to scale up HIV testing in order to reach the first 90.

Increasing HIV testing among pregnant women in Nigeria: evaluating the traditional birth attendant and primary health center integration (TAP-In) model.

Chizoba AF, Pharr JR, Oodo G, Ezeobi E, Ilozumb J, Egharevba J, Ezeanolue EE, Nwandu A. AIDS Care. 2017 Apr 18:1-5. doi: 10.1080/09540121.2017.1317325. [Epub ahead of print]

Engaging Traditional Birth Attendants (TBAs) may be critical to preventing mother-to-child transmission of HIV (PMTCT) in Nigeria. We integrated TBAs into Primary Health Centers (PHCs) and provided the TBAs with HIV counseling and testing (HCT) training for PMTCT (TAP-In). The purpose of this study was to evaluate the impact of TAP-In on HCT uptake among pregnant women. A quasi-experimental design was used for this study. Twenty PHCs were assigned to the intervention group that integrated TAP-In and 20 were assigned to the control group. Data were collected six months prior to the initiation of TAP-In and six months post, using antenatal clinic registries. Intervention PHCs more than doubled the number of pregnant women who received HCT in their catchment area post TAP-In while control PHCs had no significant change. After initiating TAP-In, intervention PHCs provided almost three times more HCT than the control PHCs (p < 0.01) with TBA provided over half of the HCT post TAP-In. The TAP-In model was effective for increasing HCT among pregnant women.

Abstract access 

Should trained lay providers perform HIV testing? A systematic review to inform World Health Organization guidelines.

Kennedy CE, Yeh PT, Johnson C, Baggaley R. AIDS Care. 2017 Apr 24:1-7. doi:10.1080/09540121.2017.1317710. [Epub ahead of print.]

New strategies for HIV testing services (HTS) are needed to achieve UN 90-90-90 targets, including diagnosis of 90% of people living with HIV. Task-sharing HTS to trained lay providers may alleviate health worker shortages and better reach target groups. We conducted a systematic review of studies evaluating HTS by lay providers using rapid diagnostic tests (RDTs). Peer-reviewed articles were included if they compared HTS using RDTs performed by trained lay providers to HTS by health professionals, or to no intervention. We also reviewed data on end-users' values and preferences around lay providers preforming HTS. Searching was conducted through 10 online databases, reviewing reference lists, and contacting experts. Screening and data abstraction were conducted in duplicate using systematic methods. Of 6113 unique citations identified, 5 studies were included in the effectiveness review and 6 in the values and preferences review. One US-based randomized trial found patients' uptake of HTS doubled with lay providers (57% vs. 27%, percent difference: 30, 95% confidence interval: 27-32, p < 0.001). In Malawi, a pre/post study showed increases in HTS sites and tests after delegation to lay providers. Studies from Cambodia, Malawi, and South Africa comparing testing quality between lay providers and laboratory staff found little discordance and high sensitivity and specificity (≥98%). Values and preferences studies generally found support for lay providers conducting HTS, particularly in non-hypothetical scenarios. Based on evidence supporting using trained lay providers, a WHO expert panel recommended lay providers be allowed to conduct HTS using HIV RDTs. Uptake of this recommendation could expand HIV testing to more people globally.

Abstract  Full-text [free] access

Africa, Asia
  • share
0 comments.

How do we know which activities make a difference to HIV prevention?

Editor’s notes: In order to be fairly certain that an intervention is responsible for changes in HIV or HIV-related behaviours, the gold standard is randomization. This allows for fair comparisons between groups, since factors that might alter the outcomes will be more or less equally balanced between the study groups.  This is true whether such confounding factors are expected, but also importantly, even those factors that are unknown, unexpected and unmeasured will also be balanced between the arms. 

A second key determinant of high quality research is to use an approach that maximizes full engagement and follow-up of participants in the study.  One such approach that is widely recognized is to use Good Participatory Practice.  

Rhodes and colleagues study condom promotion and HIV testing among the Hispanic/Latino community of gay men and other men who have sex with men in North Carolina, USA.  Although gay men and other men who have sex with men represent approximately 4% of the adult male population in the United States of America, they account for more than 80% of new HIV infections among men.  Around one quarter of gay men and other men who have sex with men are Hispanic or Latino.  The authors therefore wanted to use research to make a difference to the HIV burden of the Hispanic/Latino gay men and other men who have sex with men community in North Carolina, USA.  They found that despite the impact of HIV on Hispanic/ Latino gay men and other men who have sex with men, they were only able to identify one evidence-based behavioural HIV prevention programme focussed on this population.

The authors used an extensive community based participatory research partnership, whose members represented the Hispanic/ Latino gay men and other men who have sex with men community, AIDS service organizations, Hispanic/Latino-serving community organizations, and universities to develop, implement, and evaluate a Spanish-language, small group intervention designed to increase condom use and HIV testing among Hispanic/Latino gay men and other men who have sex with men (HOLA en Grupos).

304 participants were randomly allocated to the HOLA en Grupos intervention, or to a general health education comparison intervention having the same number of sessions (4) and duration (16 hours in total) that focussed on prostate, lung, and colorectal cancers; diabetes; high cholesterol; cardiovascular disease; and alcohol misuse. These topics for the control group were identified on the basis of identified needs and priorities of Hispanic/Latino gay men and other men who have sex with men.

HOLA en Grupos is grounded on social cognitive theory, empowerment education, and traditional Hispanic/Latino cultural values and includes four interactive modules of four hours each delivered in groups.  Participants in both intervention and control arms received reimbursement for their time, certificates of completion and meals and a celebration at the completion of the course.  In other words this was an intensive intervention that might be hard to replicate in most settings, but it follows very high standards both for developing and conducting the research and also for determining the impact of the intervention.

The intervention was associated with a large effect on both condom usage (four-fold higher in the intervention arm than the control) and HIV test uptake (an astonishing 14-fold higher, reflecting the relatively low testing rate in the control group).

A major limitation in many HIV prevention studies, including this one, is that the outcome is based on reported behaviour.  The challenge is that the real outcome of interest, which is new HIV infections, is relatively rare in almost all communities so that studies have to be huge and expensive, and the large majority of participants in both intervention and control arms do not in fact acquire HIV.  This is in contrast to most studies of treatment, where there are clearly defined biological, standardized measures which many or all participants are likely to reach.  Nonetheless, there are many examples of studies that find changes in reported behaviour that are not associated with biological markers of such change (such as incidence of HIV or other sexually transmitted infections, or pregnancy). 

There are also many observational or ecological studies that report changes in new HIV infections but that cannot truly say why the number of infections fell and whether the interventions used in the study were responsible for the changes.  For example Nwokolo and colleagues report in a short research letter on the dramatic decline in new HIV diagnoses in the large London clinic where they work.  New infections in that clinic, and in fact in other large clinics in London, have dropped by a remarkable 40% from 2015 to 2016, as originally reported in the popular science press before any scientific publication or presentation. The authors of the research letter are suitably cautious about how to account for the impressive decline.  Various systems have been improved over the past few years in this clinic to make it easier to have an HIV test and start treatment immediately.  However, most of the clinic team (and many other commentators) assume that it is also due to the rapid rise in the use of PrEP.  Although it is still not available through the UK National Health Service, the clinic has been at the forefront of encouraging gay men and other men who have sex with men who might benefit from PrEP to purchase it from on-line pharmacies.  The clinic then provides the appropriate monitoring and follow up to ensure that their clients get the best possible PrEP service given the current constraints.  Whatever the cause, we should be celebrating the rapid fall in new HIV infections across London, which is home to a substantial proportion of the new HIV infections in the UK.

The challenges of demonstrating evidence of effectiveness for HIV prevention is also felt among black women in the USA.  Although they have the highest burden of HIV among women in the USA, the incidence rates are such that a traditional randomized trial design would need to be huge, and consequently hugely expensive.  Adimora and colleagues consider whether an alternative trial design might be to use data from high HIV incidence settings and then to develop proxies of protection, such as the concentration of a PrEP medicine to infer whether black women are protected.  An alternative that has been proposed for men who have sex with men would be to look for other markers of high risk, such as sexually transmitted infections, reported partners, age, and substance use and estimate the likely risk of HIV acquisition in the absence of PrEP from these parameters.  Then the observed incidence could be compared to this modelled counterfactual, much as was done in the open label extension of the Partners PrEP study in Kenyan and Ugandan sero-different couples.  However, translating risk factors for infection across populations, and even continents when there is such heterogeneity in risk of infection is not at all straightforward.  So there is still plenty to think about and no clear answers yet!

A useful addition to the tool box for designing studies and assessing the effectiveness of interventions, would be better tools for measuring recent infection.  There are several assays all with differing characteristics but increasingly these differences and how they interact with different clades of HIV are becoming clear.  Key determinants for each assay are the mean duration of recent infection (MDRI) estimate (which does seem to vary by clade) and the false recency rate (FRR) which needs to be less than 2% to be considered useful.  Hargrove and colleagues used three different assays to test samples from 101 women who seroconverted during the ZVITAMBO trial.  The MDRI measured using standard cut-off points, were considerably shorter than those published for the general population.  The authors point out that changes in antibody properties among women who have recently given birth or other unspecified physiological states, mean that incidence assays may give different results from those published and expected.  Yet more caution when comparing incidence estimates between studies.  As an endpoint in a comparison between two groups in the same population, the assays are still attractive. Although, given typical MDRIs of around six to nine months, these assays will still need to be embedded in very large samples to give reliable estimates of incidence and statistically significant differences between groups.

This month saw the production of a useful supplement on many aspects of how data from different sources, including incidence assays are used to inform the sophisticated models on which so much HIV planning, programming and financing is based.  An example is Mahiane and colleagues’ paper on the development of a new tool to fit existing programme data into the spectrum suite of models in order to estimate incidence.

Finally in this section, for those who are keen on laboratory studies, Richardson-Harman and colleagues describe the current state of ex-vivo challenge models for assessing potential candidates as microbicides.  In these models, biopsies of rectal, cervical or vaginal tissue, taken during other procedures, or from volunteers, are kept alive in the laboratory.  The tissues can then be challenged with HIV in the presence or absence of potential microbicide products.  The current model works best for rectal tissues, in which infection occurs promptly and consistently, so that the effect of a microbicide can clearly be seen by a reduction in the production of HIV p24 antigen.  However, for cervical and vaginal tissues, the infection (in the absence of any microbicide) was less consistent, slower and lasted longer making it less easy to determine statistical differences between those tissues with microbicide and those without.  Further work of this sort may help to streamline the choice of microbicide or PrEP products that can most sensibly be taken out of the laboratory and into the (almost) real world of clinical trials.

Small-group randomized controlled trial to increase condom use and HIV testing among Hispanic/Latino gay, bisexual, and other men who have sex with men.

Rhodes SD, Alonzo J, Mann L, Song EY, Tanner AE, Arellano JE, Rodriguez-Celedon R, Garcia M, Freeman A, Reboussin BA, Painter TM. Am J Public Health. 2017 Jun;107(6):969-976. doi: 10.2105/AJPH.2017.303814. Epub 2017 Apr 20.

Objectives: To evaluate the HOLA en Grupos intervention, a Spanish-language small-group behavioral HIV prevention intervention designed to increase condom use and HIV testing among Hispanic/Latino gay, bisexual, and other men who have sex with men.

Methods: In 2012 to 2015, we recruited and randomized 304 Hispanic/Latino men who have sex with men, aged 18 to 55 years in North Carolina, to the 4-session HOLA en Grupos intervention or an attention-equivalent general health education comparison intervention. Participants completed structured assessments at baseline and 6-month follow-up. Follow-up retention was 100%.

Results: At follow-up, relative to comparison participants, HOLA en Grupos participants reported increased consistent condom use during the past 3 months (adjusted odds ratio [AOR] = 4.1; 95% confidence interval [CI] = 2.2, 7.9; P < .001) and HIV testing during the past 6 months (AOR = 13.8; 95% CI = 7.6, 25.3; P < .001). HOLA en Grupos participants also reported increased knowledge of HIV (P < .001) and sexually transmitted infections (P < .001); condom use skills (P < .001), self-efficacy (P < .001), expectancies (P < .001), and intentions (P < .001); sexual communication skills (P < .01); and decreased fatalism (P < .001).

Conclusions: The HOLA en Grupos intervention is efficacious for reducing HIV risk behaviors among Hispanic/Latino men who have sex with men.

Abstract access 

Not just PrEP: other reasons for London's HIV decline.

Nwokolo N, Whitlock G, McOwan A. Lancet HIV. 2017 Apr;4(4):e153. doi: 10.1016/S2352-3018(17)30044-9.

The reduction in HIV diagnoses in London in 2016 is attributed to pre-exposure prophylaxis (PrEP). We believe that the causes of the 42% decline seen at our clinic are likely to be multifactorial. 56 Dean Street diagnoses one in four of London's HIV cases, 50% of whom have incident infection (ie, within 4 months of infection). Because of this, and following the results of the START study, we actively recommend treatment at, or close to, diagnosis, reducing the risk of transmission in people who would otherwise be highly infectious.

Abstract access 

US black women and HIV prevention: time for new approaches to clinical trials.

Adimora AA, Cole SR, Eron JJ Clin Infect Dis. 2017 Apr 5. doi: 10.1093/cid/cix313. [Epub ahead of print]. 

Black women bear the highest burden of HIV infection among US women. Tenofovir/ emtricitabine HIV prevention trials among women in Africa have yielded varying results. Ideally, a randomized controlled trial (RCT) among US women would provide data for guidelines for US women's HIV pre-exposure prophylaxis use. However, even among US black women at high risk for HIV infection, sample size requirements for an RCT with HIV incidence as its outcome are prohibitively high. We propose to circumvent this large sample size requirement by evaluating relationships between HIV incidence and drug concentrations measured among participants in traditional phase 3 trials in high incidence settings - and then applying these observations to drug concentrations measured among at risk individuals in lower incidence settings, such as US black women. This strategy could strengthen the evidence base to enable black women to fully benefit from prevention research advances and decrease racial disparities in HIV rates.

Abstract access 

Heightened HIV antibody responses in postpartum women as exemplified by recent infection assays: implications for incidence estimates.

Hargrove JW, van Schalkwyk C, Humphrey JH, Mutasa K, Ntozini R, Owen SM, Masciotra S, Parekh BS, Duong YT, Dobbs T, Kilmarx PH, Gonese E. AIDS Res Hum Retroviruses. 2017 May 24. doi: 10.1089/AID.2016.0319. [Epub ahead of print].

Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations, and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. We determined MDRIs for multi-subtype peptide representing subtypes B, E and D (BED)-capture enzyme immunoassay, limiting antigen (LAg), and Bio-Rad Avidity Incidence (BRAI) assays for 101 seroconverting postpartum women, recruited in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers and Babies trial, comparing them against published MDRIs estimated from seroconverting cases in the general population. We also compared MDRIs for women who seroconverted either during the first 9 months, or at later stages, postpartum. At cutoffs (C) of 0.8 for BED, 1.5 for LAg, and 40% for BRAI, estimated MDRIs for postpartum mothers were 192, 104, and 144 days, 33%, 32%, and 52% lower than published estimates of 287, 152 and 298 days, respectively, for clade C samples from general populations. Point estimates of MDRI values were 7%-19% shorter for women who seroconverted in the first 9 months postpartum than for those seroconverting later. MDRI values for three HIV incidence biomarkers are longer in the general population than among postpartum women, particularly those who recently gave birth, consistent with heightened immunological activation soon after birth. Our results provide a caution that MDRI may vary significantly between subjects in different physiological states.

Abstract access 

Improvements in Spectrum's fit to program data tool.

Mahiane SG, Marsh K, Grantham K, Crichlow S, Caceres K, Stover J.  AIDS. 2017 Apr;31 Suppl 1:S23-S30. doi: 10.1097/QAD.0000000000001359.

Objective: The Joint United Nations Program on HIV/AIDS-supported Spectrum software package (Glastonbury, Connecticut, USA) is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with program and vital registration data, such as historical trends in the number of newly diagnosed infections or people living with HIV and AIDS related deaths. This article describes development and application of the fit to program data (FPD) tool in Joint United Nations Program on HIV/AIDS' 2016 estimates round.

Methods: In the FPD tool, HIV incidence trends are described as a simple or double logistic function. Function parameters are estimated from historical program data on newly reported HIV cases, people living with HIV or AIDS-related deaths. Inputs can be adjusted for proportions undiagnosed or misclassified deaths. Maximum likelihood estimation or minimum chi-squared distance methods are used to identify the best fitting curve. Asymptotic properties of the estimators from these fits are used to estimate uncertainty.

Results: The FPD tool was used to fit incidence for 62 countries in 2016. Maximum likelihood and minimum chi-squared distance methods gave similar results. A double logistic curve adequately described observed trends in all but four countries where a simple logistic curve performed better.

Conclusion: Robust HIV-related program and vital registration data are routinely available in many middle-income and high-income countries, whereas HIV seroprevalence surveillance and survey data may be scarce. In these countries, the FPD tool offers a simpler, improved approach to estimating HIV incidence trends.

Abstract access 

Analytical advances in the ex vivo challenge efficacy assay.

Richardson-Harman N, Parody R, Anton P, McGowan I, Doncel G, Thurman AR, Herrera C, Kordy K, Fox J, Tanner K, Swartz G, Dezzutti CS. AIDS Res Hum Retroviruses. 2017 Apr;33(4):395-403. doi: 10.1089/AID.2016.0073. Epub 2016 Dec 16.

The ex vivo challenge assay is being increasingly used as an efficacy endpoint during early human clinical trials of HIV prevention treatments. There is no standard methodology for the ex vivo challenge assay, although the use of different data collection methods and analytical parameters may impact results and reduce the comparability of findings between trials. In this analysis, we describe the impact of data imputation methods, kit type, testing schedule and tissue type on variability, statistical power, and ex vivo HIV growth kinetics. Data were p24 antigen (pg/ml) measurements collected from clinical trials of candidate microbicides where rectal (n = 502), cervical (n = 88), and vaginal (n = 110) tissues were challenged with HIV-1BaL ex vivo. Imputation of missing data using a nonlinear mixed effect model was found to provide an improved fit compared to imputation using half the limit of detection. The rectal virus growth period was found to be earlier and of a relatively shorter duration than the growth period for cervical and vaginal tissue types. On average, only four rectal tissue challenge assays in each treatment and control group would be needed to find a one log difference in p24 to be significant (alpha = 0.05), but a larger sample size was predicted to be needed for either cervical (n = 21) or vaginal (n = 10) tissue comparisons. Overall, the results indicated that improvements could be made in the design and analysis of the ex vivo challenge assay to provide a more standardized and powerful assay to compare efficacy of microbicide products.

Abstract access 

  • share
0 comments.