Articles tagged as "United Republic of Tanzania"

Improving access to HIV testing—still the most important step to improve the lives of people living with HIV?

Editor’s notes: The target for HIV testing is very clear and well understood as the first 90 in the UNAIDS treatment targets. However, estimating the proportion of people living with HIV who know their status is not completely straightforward.  UNAIDS uses various data sources and a well described algorithm to make its annual estimates.  For some countries, population based surveys allow a random sample of the population to be interviewed and tested for HIV.  Nonetheless, such surveys only occur periodically and so data may be out of date.  People who were HIV-negative a few years ago may now be HIV positive and people who know that they were tested a few years ago and think that they know their status may in fact have acquired HIV in the meantime.  Staveteig and colleagues have used the most recent demographic and health surveys from 16 countries in sub-Saharan Africa to estimate the first 90 and to analyse the demographic characteristics associated with knowing one’s HIV status.  The authors discuss some of the challenges in the assumptions needed for this estimation process.  However, the surveys had excellent participation and a high rate of acceptance of HIV testing, so that out of more than 14 000 people living with HIV across the countries, the authors are able to state that 54% know their status.  The proportion in different countries ranges from 26% in Sierra Leone to 84% in Rwanda.  Their analysis does not present very surprising associations.  We have come to expect that men, young people and those with less than primary education are found to be less likely to know their status.  However, the study provides a direct estimate from survey data and as such helps to triangulate with other estimates from the region.

In general, the West and Central African region lags behind the East and Southern African region when it comes to access to HIV testing, linkage to treatment and viral suppression.  A catch-up plan has been developed and endorsed at high level political meetings in most countries in the region. The study by Inghels and colleagues from Côte d’Ivoire is therefore important.  They demonstrate that among 273 people recently diagnosed with HIV at the blood donors’ centre, almost half could have been diagnosed up to five years earlier if health care staff had followed guidelines to propose testing for indicator clinical conditions such as extreme weight loss, repeated fevers or shingles.  Approximately a quarter of people recently diagnosed with HIV had recognized risk factors for HIV (apart from their clinical presentation), but only approximately one-sixth, a small minority, of people had mentioned it to their heathcare professional.  If we are to catch up and ensure that 90% of people living with HIV have known their status by 2020, we need to maximize efforts to use a full range of differentiated HIV testing approaches.  Health care staff must offer HIV tests routinely to people with clinical indicator conditions. Staff at all levels of the health system must also promote an environment in which people with risk behaviours for HIV infection feel comfortable to be able to raise it and discuss it.

Reaching the 'first 90': gaps in coverage of HIV testing among people living with HIV in 16 African countries.

Staveteig S, Croft TN, Kampa KT, Head SK. PLoS One. 2017 Oct 12;12(10):e0186316. doi: 10.1371/journal.pone.0186316. eCollection 2017.

Background: UNAIDS has recently proposed a set of three ambitious targets that, if achieved, are predicted to end the AIDS epidemic by 2030. The targets, known as 90-90-90, call for 90% of people living with HIV (PLHIV) to know their status, 90% of PLHIV to receive antiretroviral therapy, and 90% of those on antiretroviral therapy to achieve viral suppression by the year 2020. We examine the first of these targets, focusing on sub-Saharan Africa, the region of the world most affected by HIV, to measure the proportion of PLHIV estimated to know their HIV status, and to identify background and behavioral characteristics significantly associated with gaps in ever testing among PLHIV.

Methods and findings: We analyze cross-sectional population-based data from the Demographic and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) fielded since 2010 in 16 sub-Saharan African countries where voluntary serological testing was recently conducted: Burkina Faso, Cameroon, Chad, Cote d'Ivoire, Ethiopia, Gabon, Lesotho, Malawi, Namibia, Rwanda, Sierra Leone, Tanzania, Togo, Uganda, Zambia, and Zimbabwe. Survey response rates averaged 95.0% (range 89.3-99.5%), while consent to serotesting averaged 94.9% (range 88.7-99.6%). This study, which includes more than 14 000 respondents living with HIV, finds that 69% of PLHIV in the average study country have ever been tested for HIV (range 34-95%). Based on timing of the last test and on ART coverage, we estimate that 54% of PLHIV in the average country are aware of their status (range 26-84%). Adjusted logistic regression finds that men (median adjusted odds ratio [AOR] = 0.38), adults with less than primary education (median AOR = 0.31), and adolescents (median AOR = 0.32) are consistently less likely to have ever been tested for HIV than women, adults with secondary and above education, and adults age 30-39, respectively. In most countries unadjusted logistic regression also finds significant gaps in testing among the poorest groups and those reporting never having had sex.

Conclusion: The fact that an average of 54% of PLHIV in these 16 countries are estimated to know their status reflects encouraging progress. However, not only is this average far short of the 90% target set by UNAIDS for 2020, but it also implies that in the average study country nearly one-half of PLHIV are unable to access lifesaving care and treatment because they are unaware that they are HIV-positive. Several gaps in HIV testing coverage exist, particularly among adolescents, the least educated, and men. While the need to target demographic groups at greatest risk of HIV continues, additional interventions focused on reaching men and on reaching socially vulnerable populations such as adolescents, the poorest, and the least educated are essential.

Abstract  Full-text [free] access 

Missed opportunities for HIV testing among newly diagnosed HIV-infected adults in Abidjan, Côte d'Ivoire.

Inghels M, Niangoran S, Minga A, Yoboue JM, Dohoun L, Yao A, Eholié S, Anglaret X, Danel C. PLoS One. 2017 Oct 4;12(10):e0185117. doi: 10.1371/journal.pone.0185117. eCollection 2017

Background: HIV testing is crucial for starting ART earlier in HIV-infected people. We describe Missed Opportunities (MO) for HIV testing among adults newly diagnosed with HIV in Abidjan, Côte d'Ivoire.

Methods: Between April 2nd 2013 and April 1st 2014, a cross-sectional study was conducted among all adults newly diagnosed (< 1year) for HIV at the Blood Donors Medical Center of Abidjan with face to face questionnaire. An MO for HIV testing was defined as a medical consultation for a clinical indicator (e.g. symptoms, hospitalization, and pregnancy) or a non-clinical indicator (e.g. high-risk sexual behavior, HIV-infected partner) potentially related to an HIV infection but did not lead to HIV test proposal by a health care professional.

Results: Of the 341 patients who attended the center during this period, 273 (157 women and 116 men) were included in this analysis. 130 (47.6%) reported at least one medical consultation for an indicator relevant for a test proposal between 1 month and five years prior to their diagnosis. Among them, 92 (77.3%) experienced at least one MO for testing. The 273 included patients reported a total of 216 indicators; 146 (67.6%) were reported without test proposal and thus were MO. Hospitalization, extreme loss of weight, chronic or repeat fever and herpes zoster were the indicators with the largest number of MO. While 66 (24.2%) patients experienced non-clinical indicators relevant to risk of HIV infection, only 11 (4.0%) mentioned it to a health professional.

Conclusion: MO for HIV testing are frequent, even in situations for which testing is clearly recommended. Better train healthcare professionals and creating new opportunities of testing inside and, outside of medical settings are crucial to improve HIV control.

Abstract  Full-text [free] access

Africa
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Cryptoccal meningitis – the unacceptable consequence of leaving people behind during ART scale up

Editor’s notes: Cryptococcal meningitis is a severe disease that occurs in people with advanced immune suppression.  Its occurrence is an indicator that an HIV treatment programme is not working well, as it is rare in people whose CD4 count is above 100 cells per microlitre.  Rajasingham and colleagues have tried to estimate the current burden of disease.  This is not straightforward, as the number and proportion of people with advanced HIV disease is changing with the increasing scale up of antiretroviral therapy and earlier HIV diagnosis.  Nonetheless, severe immune suppression still occurs in those whose HIV infection remains undiagnosed or is diagnosed too late; among those who are not started on effective ARVs promptly and among those in whom ART fails and who are not managed effectively by the ART treatment programme.  The authors estimate that there could be more than 180 000 deaths from cryptococcal meningitis with the large majority (136 000) in Africa.  This makes Cryptococcus responsible for more than 15% of HIV-related deaths, second only to tuberculosis as a documented cause.  The authors emphasize the need for earlier diagnosis of HIV and better linkage to quality care programmes.  In the meantime, there are also advances in the screening, prophylaxis and treatment of Cryptococcus itself, which require investment in laboratory services and affordable medicines that can save lives until the effects of good ART improves the immune status.

Cassim and colleagues have developed a novel approach to costing different approaches to the roll out of technology for screening for cryptococcal antigen in the blood of people with advanced HIV infection.  Depending on the numbers of samples to be tested in the laboratory, a mix of single use lateral flow assays and automated enzyme immunoassays makes most sense.  The aim is to allow the more cost-effective high-volume sites to subsidize the low volume sites in order to ensure that as many people living with advanced HIV infection as possible can be screened.

Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, Denning DW, Loyse A, Boulware DR. Lancet Infect Dis. 2017 Aug;17(8):873-881. doi: 10.1016/S1473-3099(17)30243-8. Epub 2017 May 5.

Background: Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease.

Methods: We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis.

Findings: We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8-6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500-340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600-282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600-193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400-234 300), with 135 900 (75%; [95% CI 93 900-163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10-19).

Interpretation: Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority.

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Estimating the cost-per-result of a national reflexed cryptococcal antigenaemia screening program: Forecasting the impact of potential HIV guideline changes and treatment goals

Cassim N, Coetzee LM, Schnippel K, Glencross DK. PLoS One. 2017 Aug 22;12(8):e0182154. doi: 10.1371/journal.pone.0182154. eCollection 2017.

Introduction: During 2016, the National Health Laboratory Service (NHLS) introduced laboratory-based reflexed Cryptococcal antigen (CrAg) screening to detect early Cryptococcal disease in immunosuppressed HIV+ patients with a confirmed CD4 count of 100 cells/μl or less.

Objective: The aim of this study was to assess cost-per-result of a national screening program across different tiers of laboratory service, with variable daily CrAg test volumes. The impact of potential ART treatment guideline and treatment target changes on CrAg volumes, platform choice and laboratory workflow are considered.

Methods: CD4 data (with counts ≤ 100 cells/μl) from the fiscal year 2015/16 were extracted from the NHLS Corporate Date Warehouse and used to project anticipated daily CrAg testing volumes with appropriately-matched CrAg testing platforms allocated at each of 52 NHLS CD4 laboratories. A cost-per-result was calculated for four scenarios, including the existing service status quo (Scenario-I), and three other settings (as Scenarios II-IV) which were based on information from recent antiretroviral (ART) guidelines, District Health Information System (DHIS) data and UNAIDS 90/90/90 HIV/AIDS treatment targets. Scenario-II forecast CD4 testing offered only to new ART initiates recorded at DHIS. Scenario-III projected all patients notified as HIV+, but not yet on ART (recorded at DHIS) and Scenario-IV forecast CrAg screening in 90% of estimated HIV+ patients across South Africa (also DHIS). Stata was used to assess daily CrAg volumes at the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles across 52 CD4-laboratories. Daily volumes were used to determine technical effort/ operator staff costs (% full time equivalent) and cost-per-result for all scenarios.

Results: Daily volumes ranged between 3 and 64 samples for Scenario-I at the 5th and 95th percentile. Similarly, daily volumes ranges of 1-12, 2-45 and 5-100 CrAg-directed samples were noted for Scenario's II, III and IV respectively. A cut-off of 30 CrAg tests per day defined use of either LFA or EIA platform. LFA cost-per-result ranged from $8.24 to $5.44 and EIA cost-per-result between $5.58 and $4.88 across the range of test volumes. The technical effort across scenarios ranged from 3.2-27.6% depending on test volumes and platform used.

Conclusion: The study reported the impact of programmatic testing requirements on varying CrAg test volumes that subsequently influenced choice of testing platform, laboratory workflow and cost-per-result. A novel percentiles approach is described that enables an overview of the cost-per-result across a national program. This approach facilitates cross-subsidisation of more expensive lower volume sites with cost-efficient, more centralized higher volume laboratories, mitigating against the risk of costing tests at a single site.

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Women know what they want, but need more reproductive health choices

Editor’s notes: Eliminating new HIV infections among children is often seen as a useful barometer of the overall success of the health systems as it relates to HIV.  Combination prevention approaches that include structural, behavioural and biomedical elements reduce the chance of women becoming HIV-positive.  Effective provision of a range of choices of modern contraceptive technology allow women to choose whether and when to have babies.  The option B+ approach should ensure that all pregnant women living with HIV are offered lifelong ART, which minimises the chance of mother to child transmission of HIV infection.  Continuing ART treatment for life keeps the mother healthy and allows her to support the development of her infant.

New HIV infections in children have declined by 46% since 2010, but there were still an estimated 160 000 new infections in 2016.  We know that in many settings the health system barometer is still forecasting plenty of clouds among the bright spells.  This month saw a range of papers describing reproductive health choices and HIV, as well as reflections on how option B+ is working, now that it is standard of care.

Contraceptive choices for women at high risk of HIV or living with HIV are complicated.  WHO recently reclassified long-acting progestin injections, such as DMPA, for women at high risk of HIV infection as category 2 in the Medical Eligibility for Contraception guidance. Category 2 means that, although the method is generally safe to use, clinical judgment and careful follow up may be required.  While the evidence comes from meta-analyses of observational studies, with inherent limitations, there is a reliable association between new HIV infection and the use of injectable progestins.  The ongoing randomized ECHO trial will provide higher quality evidence of causality, but results will not be reported until 2019. 

Mayhew et al. found that women living with HIV attending clinics in Kenya, were quite clear about their fertility intentions.  Many did not want more children, although they acknowledged pressure from partners and others.  Stigma around breast-feeding, worries about money and about possible health consequences of pregnancy were all reasons to decide not to have further children. The large majority used various sorts of contraception, but despite this 40% of pregnancies during the study were unintended.  The authors felt that the advice given by the clinics was not adequate and that choice of contraceptive method was limited.  In particular reliable long-acting methods, both reversible and not, were rarely taken up by the younger women.  Overall 16% of women used long-acting methods, and no pregnancies occurred in this group.

Chanda et al. focused on female sex workers in Zambia and found similar results.  Almost half the women had had terminations of pregnancies, and 62% of pregnancies were not planned.  Interestingly the availability of condoms at their places of work reduced the chances of unwanted pregnancy.  Approximately 39% used injectable long-acting contraceptives and only 18% used dual protection with a barrier in addition to a non-barrier method.  Less than one-third of the women reported that condoms were available often or always at work, and 23% reported using no contraception.  Providing access to condoms for sex workers in the highest transmission areas of countries like Zambia seems such an obvious pre-requisite for HIV programmes that it is extraordinary that in 2017 we still do not manage to do so.

Finally on this theme, Salters et al. demonstrate that contraceptive choice for women living with HIV is not only a challenge in sub-Saharan Africa.  The authors followed women in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study and showed that 61% of reported pregnancies were unintended. Women with unintended pregnancies tended to be younger, single and born in Canada compared to women with planned pregnancies.  To support the second prong of the strategy to eliminate HIV infections in children, we need to improve on the integration between services for sexual and reproductive health and rights and services for women living with HIV.

Once women living with HIV are pregnant, the focus shifts to the third and fourth prong – preventing transmission to the infant and keeping the mother and infant healthy.  Option B+ has transformed the approach in most antenatal clinics with high rates of coverage of HIV testing and most women receiving ART during pregnancy.  In the One Stop Clinic in Ifakara, Tanzania, Gamell et al. show that almost all pregnant women, who do not already know that they are living with HIV, are offered an HIV test and that 94% accept it.  Retesting late in pregnancy is not yet routine, and only 3% were re-tested, of whom one (2%) had seroconverted.  Since acute HIV infection has such an important impact on the risk of transmission, re-testing later in pregnancy is now routine in many countries.  Coverage is far from complete, so it is not always clear whether the high rates of seroconversion observed reflect a selection bias in choosing women who are at particularly high risk.  This is an important area for research if we are to continue to drive down the already low transmission rates.  Similarly the authors found that women who slipped through the net and presented in labour, were not always tested and did have a higher prevalence of infection - 5.2% vs. 3.1%. The other significant finding in Ifakara was that, as in many cohort studies, women were happy to take ART during pregnancy to protect their infants, but retention in care thereafter was much less impressive.  Of women newly diagnosed with HIV infection during pregnancy, 27% were lost to follow up at the time of the analysis.

Chadambuka et al. used qualitative methods to understand what impact the shift to option B+ has had in their study area in Zimbabwe.  Overall, the women interviewed were very positive about treatment.  They believed that it was good for their babies and also good for them, making them look healthy and thus avoiding stigma.  However, women pointed out that their male partners are not exposed to as much information at the clinic or in the community.  As a result, many men are less keen to be tested and sometimes not keen for their partners to be taking medicine despite appearing healthy.  As one woman put it: “Very few men are supportive. You have to be strong. The men base their judgment on how healthy you appear to be as you carry yourself around and he also compares to how healthy he feels and opts to delay testing. But delaying only brings further harm. So when those men tell you to stop taking your medication, you need to tell them that they can stop if they want to, whilst you continue with your treatment.”  Within the power dynamics of many relationships, such a forthright approach may not be easy for all women.  So we need continued attention on how to engage men in the process and how to empower women to act as agents of change within their communities.

 

Fertility intentions and contraceptive practices among clinic-users living with HIV in Kenya: a mixed methods study

Mayhew SH, Colombini M, Kimani JK, Tomlin K, Warren CE; Integra Initiative, Mutemwa R. BMC Public Health. 2017 Jul 5;17(1):626. doi: 10.1186/s12889-017-4514-2.

Background: Preventing unwanted pregnancies in Women Living with HIV (WLHIV) is a recognised HIV-prevention strategy. This study explores the fertility intentions and contraceptive practices of WLHIV using services in Kenya.

Methods: Two hundred forty women self-identifying as WLHIV who attended reproductive health services in Kenya were interviewed with a structured questionnaire in 2011; 48 were also interviewed in-depth. STATA SE/13.1, Nvivo 8 and thematic analysis were used.

Results: Seventy one percent participants did not want another child; this was associated with having at least two living children and being the bread-winnerFP use was high (92%) but so were unintended pregnancies (40%) while living with HIV. 56 women reported becoming pregnant "while using FP": all were using condoms or short-term methods. Only 16% participants used effective long-acting reversible contraceptives or permanent methods (LARC-PM). Being older than 25 years and separated, widowed or divorced were significant predictors of long-term method use. Qualitative data revealed strong motivation among WLHIV to plan or prevent pregnancies to avoid negative health consequences. Few participants received good information about contraceptive choices.

Conclusions: WLHIV need better access to FP advice and a wider range of contraceptives including LARC to enable informed choices that will protect their fertility intentions, ensure planned pregnancies and promote safe child-bearing.

Trial registration: Integra is a non-randomised pre-post intervention trial registered with Current Controlled Trials ID: NCT01694862.

Abstract  Full-text [free] access

 

Contraceptive use and unplanned pregnancy among female sex workers in Zambia

Chanda MM, Ortblad KF, Mwale M, Chongo S, Kanchele C, Kamungoma N, Barresi LG, Harling G, Bärnighausen T, Oldenburg CE. Contraception. 2017 Sep;96(3):196-202. doi: 10.1016/j.contraception.2017.07.003. Epub 2017 Jul 12.

Objectives: Access to reproductive healthcare, including contraceptive services, is an essential component of comprehensive healthcare for female sex workers (FSW). Here, we evaluated the prevalence of and factors associated with contraceptive use, unplanned pregnancy, and pregnancy termination among FSW in three transit towns in Zambia.

Study design: Data arose from the baseline quantitative survey from a randomized controlled trial of HIV self-testing among FSW. Eligible participants were 18 years of age or older, exchanged sex for money or goods at least once in the past month, and were HIV-uninfected or status unknown without recent HIV testing (<3 months). Logistic regression models were used to assess factors associated with contraceptive use and unplanned pregnancy.

Results: Of 946 women eligible for this analysis, 84.1% had been pregnant at least once, and among those 61.6% had an unplanned pregnancy, and 47.7% had a terminated pregnancyIncarceration was associated with decreased odds of dual contraception use (aOR=0.46, 95% CI 0.32-0.67) and increased odds of unplanned pregnancy (aOR=1.75, 95% CI 1.56-1.97). Condom availability at work was associated with increased odds of using condoms only for contraception (aOR=1.74, 95% CI 1.21-2.51) and decreased odds of unplanned pregnancy (aOR=0.63, 95% CI 0.61-0.64).

Conclusions: FSW in this setting have large unmet reproductive health needs. Structural interventions, such as increasing condom availability in workplaces, may be useful for reducing the burden of unplanned pregnancy.

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Pregnancy incidence and intention after HIV diagnosis among women living with HIV in Canada

Salters K, Loutfy M, de Pokomandy A, Money D, Pick N, Wang L, Jabbari S, Carter A, Webster K, Conway T, Dubuc D, O'Brien N, Proulx-Boucher K, Kaida A; CHIWOS Research Team. PLoS One. 2017 Jul 20;12(7):e0180524. doi: 10.1371/journal.pone.0180524. eCollection 2017.

Background: Pregnancy incidence rates among women living with HIV (WLWH) have increased over time due to longer life expectancy, improved health status, and improved access to and HIV prevention benefits of combination antiretroviral therapy (cART). However, it is unclear whether intended or unintended pregnancies are contributing to observed increases.

Methods: We analyzed retrospective data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). Kaplan-Meier methods and GEE Poisson models were used to measure cumulative incidence and incidence rate of pregnancy after HIV diagnosis overall, and by pregnancy intention. We used multivariable logistic regression models to examine independent correlates of unintended pregnancy among the most recent/current pregnancy.

Results: Of 1165 WLWH included in this analysis, 278 (23.9%) women reported 492 pregnancies after HIV diagnosis, 60.8% of which were unintendedUnintended pregnancy incidence (24.6 per 1000 women-years (WYs); 95% CI: 21.0, 28.7) was higher than intended pregnancy incidence (16.6 per 1000 WYs; 95% CI: 13.8, 20.1) (Rate Ratio: 1.5, 95% CI: 1.2-1.8). Pregnancy incidence among WLWH who initiated cART before or during pregnancy (29.1 per 1000 WYs with 95% CI: 25.1, 33.8) was higher than among WLWH not on cART during pregnancy (11.9 per 1000 WYs; 95% CI: 9.5, 14.9) (Rate Ratio: 2.4, 95% CI: 2.0-3.0). Women with current or recent unintended pregnancy (vs. intended pregnancy) had higher adjusted odds of being single (AOR: 1.94; 95% CI: 1.10, 3.42), younger at time of conception (AOR: 0.95 per year increase, 95% CI: 0.90, 0.99), and being born in Canada (AOR: 2.76, 95% CI: 1.55, 4.92).

Conclusion: Nearly one-quarter of women reported pregnancy after HIV diagnosis, with 61% of all pregnancies reported as unintended. Integrated HIV and reproductive health care programming is required to better support WLWH to optimize pregnancy planning and outcomes and to prevent unintended pregnancy.

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Prevention of mother-to-child transmission of HIV Option B+ cascade in rural Tanzania: the One Stop Clinic model

Gamell A, Luwanda LB, Kalinjuma AV, Samson L, Ntamatungiro AJ, Weisser M, Gingo W, Tanner M, Hatz C, Letang E, Battegay M; KIULARCO Study Group. PLoS One. 2017 Jul 12;12(7):e0181096. doi: 10.1371/journal.pone.0181096. eCollection 2017.

Background: Strategies to improve the uptake of Prevention of Mother-To-Child Transmission of HIV (PMTCT) are needed. We integrated HIV and maternal, newborn and child health services in a One Stop Clinic to improve the PMTCT cascade in a rural Tanzanian setting.

Methods: The One Stop Clinic of Ifakara offers integral care to HIV-infected pregnant women and their families at one single place and time. All pregnant women and HIV-exposed infants attended during the first year of Option B+ implementation (04/2014-03/2015) were includedPMTCT was assessed at the antenatal clinic (ANC), HIV care and labour ward, and compared with the pre-B+ period. We also characterised HIV-infected pregnant women and evaluated the MTCT rate.

Results: 1579 women attended the ANC. Seven (0.4%) were known to be HIV-infectedOf the remainder, 98.5% (1548/1572) were offered an HIV test94% (1456/1548) accepted and 38 (2.6%) tested HIV-positive51 were re-screened for HIV during late pregnancy and one had seroconvertedThe HIV prevalence at the ANC was 3.1% (46/1463). Of the 39 newly diagnosed women, 35 (90%) were linked to care. HIV test was offered to >98% of ANC clients during both the pre- and post-B+ periods. During the post-B+ period, test acceptance (94% versus 90.5%, p<0.0001) and linkage to care (90% versus 26%, p<0.0001) increasedTen additional women diagnosed outside the ANC were linked to care. 82% (37/45) of these newly-enrolled women started antiretroviral treatment (ART). After a median time of 17 months, 27% (12/45) were lost to follow-up. 79 women under HIV care became pregnant and all received ART. After a median follow-up time of 19 months, 6% (5/79) had been lost. 5727 women delivered at the hospital, 20% (1155/5727) had unknown HIV serostatus. Of these, 30% (345/1155) were tested for HIV, and 18/345 (5.2%) were HIV-positive. Compared to the pre-B+ period more women were tested during labour (30% versus 2.4%, p<0.0001). During the study, the MTCT rate was 2.2%.

Conclusions: The implementation of Option B+ through an integrated service delivery model resulted in universal HIV testing in the ANC, high rates of linkage to care, and MTCT below the elimination threshold. However, HIV testing in late pregnancy and labour, and retention during early ART need to be improved.

Abstract  Full-text [free] access

 

Acceptability of lifelong treatment among HIV-positive pregnant and breastfeeding women (Option B+) in selected health facilities in Zimbabwe: a qualitative study

Chadambuka A, Katirayi L, Muchedzi A, Tumbare E, Musarandega R, Mahomva AI, Woelk G BMC Public Health. 2017 Jul 25;18(1):57. doi: 10.1186/s12889-017-4611-2.

Background: Zimbabwe's Ministry of Health and Child Care (MOHCC) adopted 2013 World Health Organization (WHO) prevention of mother-to-child HIV transmission (PMTCT) guidelines recommending initiation of HIV-positive pregnant and breastfeeding women (PPBW) on lifelong antiretroviral treatment (ART) irrespective of clinical stage (Option B+). Option B+ was officially launched in Zimbabwe in November 2013; however the acceptability of life-long ART and its potential uptake among women was not known.

Methods: A qualitative study was conducted at selected sites in Harare (urban) and Zvimba (rural) to explore Option B+ acceptability; barriers, and facilitators to ART adherence and service uptake. In-depth interviews (IDIs), focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with PPBW, healthcare providers, and community members. All interviews were audio-recorded, transcribed, and translated; data were coded and analyzed in MaxQDA v10.

Results: Forty-three IDIs, 22 FGDs, and five KIIs were conducted. The majority of women accepted lifelong ART. There was however, a fear of commitment to taking lifelong medication because they were afraid of defaulting, especially after cessation of breastfeeding. There was confusion around dosage; and fear of side effects, not having enough food to take drugs, and the lack of opportunities to ask questions in counseling. Participants reported the need for strengthening community sensitization for Option B+. Facilitators included receiving a simplified pill regimen; ability to continue breastfeeding beyond 6 months like HIV-negative women; and partner, community and health worker support. Barriers included distance of health facility, non-disclosure of HIV status, poor male partner support and knowing someone who had negative experience on ART.

Conclusions: This study found that Option B+ is generally accepted among PPBW as a means to strengthen their health and protect their babies. Consistent with previous literature, this study demonstrated the importance of male partner and community support in satisfactory adherence to ART and enhancing counseling techniques. Strengthening community sensitization and male knowledge is critical to encourage women to disclose their HIV status and ensure successful adherence to ART. Targeting and engaging partners of women will remain key determinants to women's acceptance and adherence on ART under Option B+

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Africa, Northern America
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Understanding different levels and different models of integration

Editor’s notes: Integration between HIV services and programmes and other services and programmes sounds like common sense.  As people with HIV live longer they are more likely to develop other chronic conditions.  Some of these conditions may also be exacerbated by some anti-retroviral medicines, although modern treatment regimens have much less effect on lipid and insulin metabolism.  Low grade chronic inflammation may continue even in people whose HIV is suppressed and people whose CD4 count sunk to a low level before starting seem to be at greater risk of subsequent cardiovascular disease.  Then there are diseases that are more common among people living with HIV, such as tuberculosis and invasive cervical cancer.  And HIV programmes around the world have established some of the best clinical services for chronic care, with regular appointments, decentralized follow-up, algorithmic approaches to clinical changes and so on.  So it seems sensible to look for the synergies and build on them.

However, research on integration makes it clear that there are many different interpretations of what integration should or could mean.  In different epidemiological settings, the priorities will inevitably be very different.  Two useful systematic reviews this month by the same team, review this territory for cardiovascular diseases, diabetes and cervical cancer. 

Haldane et al. distinguish between the levels of integration.  Micro level integration involves direct patient care and adjusting diagnosis, treatment and support appropriately.  Meso level integration refers to changes made at the clinic or delivery system level, while macro level integration is about programme management, supply chains and systems organisation.  Despite a large literature (over 7600 papers) on the overlaps between HIV and cardiovascular diseases and diabetes, the authors found only 14 studies that allowed aspects of the integration to be assessed, and only one of these evaluated outcomes.  The others were descriptive studies which highlighted many innovative models, almost all at the meso-level.

Similarly for invasive cervical cancer, which is at least four times as common among women living with HIV as seronegative women, Sigfrid et al. found many papers but only 21 that met their inclusion criteria.  Their models of integration could all be said to be at the meso-level, with one stop shops; co-located services or more complex integrated pathways described.  Again, there were no good evaluations of the outcomes of these systematic changes to the way that services are delivered.  In most countries, all women with cervical cancer should at least be offered an HIV test and appropriate linkage to care expedited for those found to be seropositive.  Women living with HIV need regular screening for early cervical cancer and (as discussed last month) screening for human papillomavirus, the underlying cause of cervical cancer.  However, many ART clinics are now busy and crowded so that even if staff are trained, they do not have time or space or privacy to do cervical examinations.  HPV vaccination campaigns need to be carried out in schools before girls become sexually active.  This could be a good time to engage with sexuality education. However, many campaigns have tended to avoid the challenges of discussing sex with girls who are not yet sexually active, preferring to focus on the vaccine as a cancer prevention tool.  So, the lesson from both these papers is that we need to define more rigorously what we want to achieve with integration and then ensure that we evaluate whether or not our interventions achieve it.

Tuberculosis and HIV have been dancing together since the first descriptions of HIV in the 1980s.  The large majority of tuberculosis patients in many countries are now screened for HIV, with appropriate referral and increasing numbers of people living with HIV are screened regularly for the four classic symptoms of tuberculosis (weight loss, cough, night sweats and fever) and referred onwards for diagnosis.  Yet we still find that collaboration between programmes is not always easy. The number of people living with HIV who are also on tuberculosis treatment reported by the HIV programme may not be the same as the number of people on tuberculosis treatment who are also living with HIV reported by the tuberculosis programme.  Osei et al. report from the Volta Region of Ghana that more than 90% of tuberculosis patients had an HIV test recorded in the tuberculosis register, with an HIV prevalence of 18%.  As has been reported frequently elsewhere, the authors found that HIV was commoner in those with smear negative tuberculosis, and the outcome of treatment was less good.  Their recommendation for strengthening the collaboration between tuberculosis and HIV makes sense, although it has been WHO policy for many years.

The WHO guidance on collaborative TB/HIV activities has always included isoniazid preventive therapy.  However, this remains poorly implemented for reasons that are never very clear.  Despite no good evidence, many tuberculosis programme staff and clinicians worry about the risk of generating isoniazid resistant tuberculosis.  Many HIV programme staff feel that isoniazid remains in the realm of the tuberculosis programme, so that although they are happy to promote cotrimoxazole, they are much slower to prescribe isoniazid.  Many also feel that ART alone should be sufficient to prevent tuberculosis, despite randomized trials in high prevalence settings that demonstrate the additional benefits of isoniazid.  Shayo et al. make a strong economic argument for promoting isoniazid in their study in Tanzania.  They base their model on the rates of tuberculosis and mortality seen during the expansion of pilot programmes for isoniazid in Dar es Salaam.  Both tuberculosis and mortality were significantly lower in the clinics which were part of the pilot programme.  In fact, mortality was approximately tenfold lower, which seems unlikely to be simply due to isoniazid.  Some studies such as TEMPRANO have shown a mortality benefit from isoniazid, while many trials have failed to do so.  Given the non-randomized nature of the comparison, the authors do point out that their conclusions must be tentative.  Nonetheless, it is a convincing demonstration that isoniazid preventive therapy can be incorporated into a busy HIV care clinic and there is abundant evidence that this is the right thing to do.

One more tuberculosis study this month was carried out in Germany.  Karo et al. reviewed the immunology of the 139 people who developed tuberculosis among more than 10 000 people living with HIV in the German ClinSurv cohort.  The authors excluded people who already had tuberculosis at the time that HIV was diagnosed, and found that new diagnoses of tuberculosis were most common in the first couple of years after starting ART.  The authors also show that immune restoration was slower in people who developed tuberculosis.  There was still some deficit up to seven years after ART was started.  Again, their conclusion is that we should be using isoniazid to prevent tuberculosis in people living with HIV, especially people who have spent much of their lives in areas of the world, such as sub-Saharan Africa where tuberculosis is much more prevalent than in Europe.  It is often said that Mycobacterium tuberculosis is a very slow growing organism.  We must work harder to ensure that our response to it is not very slow too.  Tuberculosis remains the biggest killer of people with HIV in most of the world, yet for years we have known that a simple, cheap, non-toxic treatment can prevent it. 

 

Integrating cardiovascular diseases, hypertension, and diabetes with HIV services: a systematic review.

Haldane V, Legido-Quigley H, Chuah FLH, Sigfrid L, Murphy G, Ong SE, Cervero-Liceras F, Watt N, Balabanova D, Hogarth S, Maimaris W, Buse K, McKee M, Piot P, Perel P. AIDS Care. 2017 Jul 5:1-13. doi:10.1080/09540121.2017.1344350. [Epub ahead of print]

Non-communicable diseases (NCDs), including cardiovascular diseases (CVD), hypertension and diabetes together with HIV infection are among the major public health concerns worldwide. Health services for HIV and NCDs require health systems that provide for people's chronic care needs, which present an opportunity to coordinate efforts and create synergies between programs to benefit people living with HIV and/or AIDS and NCDs. This review included studies that reported service integration for HIV and/or AIDS with coronary heart diseases, chronic CVD, cerebrovascular diseases (stroke), hypertension or diabetes. We searched multiple databases from inception until October 2015. Articles were screened independently by two reviewers and assessed for risk of bias. 11 057 records were identified with 7 616 after duplicate removal. After screening titles and abstracts, 14 papers addressing 17 distinct interventions met the inclusion criteria. We categorized integration models by diseases (HIV with diabetes, HIV with hypertension and diabetes, HIV with CVD and finally HIV with hypertension and CVD and diabetes). Models also looked at integration from micro (patient focused integration) to macro (system level integrations). Most reported integration of hypertension and diabetes with HIV and AIDS services and described multidisciplinary collaboration, shared protocols, and incorporating screening activities into community campaigns. Integration took place exclusively at the meso-level, with no micro- or macro-level integrations described. Most were descriptive studies, with one cohort study reporting evaluative outcomes. Several innovative initiatives were identified and studies showed that CVD and HIV service integration is feasible. Integration should build on existing protocols and use the community as a locus for advocacy and health services, while promoting multidisciplinary teams, including greater involvement of pharmacists. There is a need for robust and well-designed studies at all levels - particularly macro-level studies, research looking at long-term outcomes of integration, and research in a more diverse range of countries.

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Integrating cervical cancer with HIV healthcare services: A systematic review.

Sigfrid L, Murphy G, Haldane V, Chuah FLH, Ong SE, Cervero-Liceras F, Watt N, Alvaro A, Otero-Garcia L, Balabanova D, Hogarth S, Maimaris W, Buse K, Mckee M, Piot P, Perel P, Legido-Quigley H. PLoS One. 2017 Jul 21;12(7):e0181156. doi: 10.1371/journal.pone.0181156. eCollection 2017.

Background: Cervical cancer is a major public health problem. Even though readily preventable, it is the fourth leading cause of death in women globally. Women living with HIV are at increased risk of invasive cervical cancer, highlighting the need for access to screening and treatment for this population. Integration of services has been proposed as an effective way of improving access to cervical cancer screening especially in areas of high HIV prevalence as well as lower resourced settings. This paper presents the results of a systematic review of programs integrating cervical cancer and HIV services globally, including feasibility, acceptability, clinical outcomes and facilitators for service delivery.

Methods: This is part of a larger systematic review on integration of services for HIV and non-communicable diseases. To be considered for inclusion studies had to report on programs to integrate cervical cancer and HIV services at the level of service delivery. We searched multiple databases including Global Health, Medline and Embase from inception until December 2015. Articles were screened independently by two reviewers for inclusion and data were extracted and assessed for risk of bias.

Main results: 11 057 records were identified initially. 7616 articles were screened by title and abstract for inclusion. A total of 21 papers reporting interventions integrating cervical cancer care and HIV services met the criteria for inclusion. All but one study described integration of cervical cancer screening services into existing HIV services. Most programs also offered treatment of minor lesions, a 'screen-and-treat' approach, with some also offering treatment of larger lesions within the same visit. Three distinct models of integration were identified. One model described integration within the same clinic through training of existing staff. Another model described integration through co-location of services, with the third model describing programs of integration through complex coordination across the care pathway. The studies suggested that integration of cervical cancer services with HIV services using all models was feasible and acceptable to patients. However, several barriers were reported, including high loss to follow up for further treatment, limited human-resources, and logistical and chain management support. Using visual screening methods can facilitate screening and treatment of minor to larger lesions in a single 'screen-and-treat' visit. Complex integration in a single-visit was shown to reduce loss to follow up. The use of existing health infrastructure and funding together with comprehensive staff training and supervision, community engagement and digital technology were some of the many other facilitators for integration reported across models.

Conclusions: This review shows that integration of cervical cancer screening and treatment with HIV services using different models of service delivery is feasible as well as acceptable to women living with HIV. However, the descriptive nature of most papers and lack of data on the effect on long-term outcomes for HIV or cervical cancer limits the inference on the effectiveness of the integrated programs. There is a need for strengthening of health systems across the care continuum and for high quality studies evaluating the effect of integration on HIV as well as on cervical cancer outcomes.

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The burden of HIV on tuberculosis patients in the Volta region of Ghana from 2012 to 2015: implication for tuberculosis control.

Osei E, Der J, Owusu R, Kofie P, Axame WK. BMC Infect Dis. 2017 Jul 19;17(1):504. doi: 10.1186/s12879-017-2598-z.

Background: The impact of HIV on TB, and the implications for TB control, has been acknowledged as a public health challenge. It is imperative therefore to assess the burden of HIV on TB patients as an indicator for monitoring the control efforts of the two diseases in this part of the world. This study aimed at determining the burden of HIV infection in TB patients.

Methods: We conducted a retrospective review of TB registers in five districts of the Volta Region of Ghana. Prevalence of TB/HIV co-infection was determined. Bivariate and multivariate logistic regression were used to identify the predictors of HIV infection among TB patients and statistical significance was set at p-value <0.05.

Results: Of the 1772 TB patients, 1633 (92.2%) were tested for HIV. The overall prevalence of TB/HIV co-infection was (18.2%; 95% CI: 16.4-20.1). The prevalence was significantly higher among females (24.1%; 95%CI: 20.8-27.7), compared to males (15.1%; 95% CI: 13.1-17.4) (p < 0.001) and among children <15 years of age (27.0%; 95% CI: 18.2-38.1), compared to the elderly ≥70 years (3.5%; 95% CI: 1.6-7.4) (p < 0.001). Treatment success rate was higher among patients with only TB (90%; 95% CI: 88.1-91.5) than among TB/HIV co-infected patients (77.0%; 95% CI: 71.7-81.7) (p < 0.001). Independent predictors of HIV infection were found to be: being female (AOR: 1.79; 95% CI: 1.38-2.13; p < 0.001); smear negative pulmonary TB (AOR: 1.84; 95% CI: 1.37-2.47; p < 0.001); and patients registered in Hohoe, Kadjebi, and Kpando districts with adjusted odds ratios of 1.69 (95% CI: 1.13-2.54; p = 0.011), 2.29 (95% CI: 1.46-3.57; p < 0.001), and 2.15 (95% CI: 1.44-3.21; p < 0.001) respectively. Patients ≥70 years of age and those registered in Keta Municipal were less likely to be HIV positive with odds ratios of 0.09 (95% CI: 0.04-0.26; p < 0.001) and 0.62 (95% CI: 0.38-0.99; p = 0.047) respectively.

Conclusion: TB/HIV co-infection rate in five study districts of the Volta region is quite high, occurs more frequently in female patients than males; among smear negative pulmonary TB patients, and children <15 years of age. Findings also demonstrate that HIV co-infection affects TB treatment outcomes adversely. Strengthening the TB/HIV collaborative efforts is required in order to reduce the burden of co-infection in patients.

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Cost-effectiveness of isoniazid preventive therapy among HIV-infected patients clinically screened for latent tuberculosis infection in Dar es Salaam, Tanzania: a prospective cohort study.

Shayo GA, Chitama D, Moshiro C, Aboud S, Bakari M, Mugusi F. BMC Public Health. 2017 Jul 19;18(1):35. doi: 10.1186/s12889-017-4597-9.

Background: One of the reasons why Isoniazid preventive therapy (IPT) for Tuberculosis (TB) is not widely used in low income countries is concerns on cost of excluding active TB. We analyzed the cost-effectiveness of IPT provision in Tanzania having ruled out active TB by a symptom-based screening tool.

Methods: Data on IPT cost-effectiveness was prospectively collected from an observational cohort study of 1283 HIV-infected patients on IPT and 1281 controls; followed up for 24 months. The time horizon for the analysis was 2 years. Number of TB cases prevented and deaths averted were used for effectiveness. A micro costing approach was used from a provider perspective. Cost was estimated on the basis of clinical records, market price or interviews with medical staff. We annualized the cost at a discount of 3%. A univariate sensitivity analysis was done. Results are presented in US$ at an average annual exchange rate for the year 2012 which was Tanzania shillings 1562.4 for 1 US $.

Results: The number of TB cases prevented was 420/100 000 persons receiving IPT. The number of deaths averted was 979/100 000 persons receiving IPT. Incremental cost due to IPT provision was US$ 170 490. The incremental cost-effective ratio was US $ 405.93 per TB case prevented and US $ 174.15 per death averted. These costs were less than 3 times the 768 US $ Gross Domestic Product (GDP) per capita for Tanzania in the year 2014, making IPT provision after ruling out active TB by the symptom-based screening tool cost-effective. The results were robust to changes in laboratory and radiological tests but not to changes in recurrent, personnel, medication and utility costs.

Conclusion: IPT should be given to HIV-infected patients who screen negative to symptom-based TB screening questionnaire. Its cost-effectiveness supports government policy to integrate IPT to HIV/AIDS care and treatment in the country, given the availability of budget and the capacity of health facilities.

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Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral therapy: implication for tuberculosis preventive therapy.

Karo B, Krause G, Castell S, Kollan C, Hamouda O, Haas W; ClinSurv HIV Study Group. BMC Infect Dis. 2017 Jul 25;17(1):517. doi: 10.1186/s12879-017-2627-y.

Background: Understanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-treated HIV-infected patients developing TB compared to those who remained free of TB.

Methods: We extracted data of HIV-infected patients from a multicenter cohort for the HIV clinical surveillance in Germany. No patients included in our study had TB at the beginning of the observation. Using a longitudinal mixed model, we assessed the differences in the mean change of biomarkers (CD4+ cell count, CD8+ cell count, CD4:CD8 ratio and viral load) since cART initiation in patients who remained free of TB vs. those developing TB. To detect the best-fit trajectories of the immunological biomarkers, we applied a multivariable fractional polynomials model.

Results: We analyzed a total of 10 671 HIV-infected patients including 139 patients who developed TB during follow-up. The highest TB incidences were observed during the first two years since cART initiation (0.32 and 0.50 per 100 person-years). In an adjusted multivariable mixed model, we found that the average change in CD4+ cell count recovery was significantly greater by 33 cells/μl in patients who remained free of TB compared with those developing TB. After the initial three months of cART, 65.6% of patients who remaining free of TB achieved CD4+ count of ≥400 cells/μl, while only 11.3% of patients developing TB reached this immunological status after the three months of cART. We found no differences in the average change of CD8+ cell count, CD4:CD8 ratio or viral load between the two-patient groups.

Conclusion: All HIV-infected patients responded to cART. However, patients developing TB showed reduced recovery in CD4+ cell count and this might partly explain the incident TB in HIV-infected patients receiving cART. These findings reinforce the importance of adjunctive TB preventive therapy for patients with reduced recovery in CD4+ cell count.

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HIV drug resistance – a manageable risk or the harbinger of a “massive second global wave”?

Editor’s notes: The Paris conference also saw the launch of the WHO report and action plan on HIV drug resistance. Laurie Garret writing in Business Insider invoked drug resistance as one of the elements that could lead to a devastating reversal in progress against HIV. Inevitably with increasing scale up of ART, drug resistance levels will begin to rise.  In the absence of robust laboratory systems to detect virological failure, the risk is that drug resistance will continue to rise and could threaten progress in some countries.  Detection and accurate diagnosis of drug resistance is routine in well-resourced health systems, but still needs to be developed in many of the countries most affected.  While switching to a standard second line regimen provides a public health approach, there will be increasing need for tailored treatment and this requires both strong laboratory systems for sequencing relevant genes, but also good bioinformatic approaches to predict the optimum treatment regimen.

Svard et al. used a split genotyping procedure to explore resistance in people failing HIV treatment in Tanzania.  This term is used to describe a procedure where the nucleic acid amplification, which requires less sophisticated laboratory systems, is performed locally.  The amplified product was then sent to Sweden, where the sequencing and bioinformatics was performed.  Tanzania does not yet have widespread access to viral load testing, so treatment failure is defined using the WHO clinical and immunological criteria.  In this study, it became clear that as many as two thirds of people thought to be failing treatment were probably not failing virologically, and so were at risk of being changed onto second (or third) line treatments unnecessarily.  So the priority should clearly be to establish viral load assays to use to detect treatment failure and to make appropriate switches in treatment.  For the minority where failure was truly associated with a raised viral load, resistance mutations showed that people with failure on first line treatment often had viruses that were also resistant to second generation NNRTIs.  Current standard second line treatment in Tanzania is with a PI based regimen.  Among the first line failure cases, the probability predicted by the bioinformatics for successful second line treatment was around 85% using the medicines registered in Tanzania, which would improve to 95% if all current medicines were available. For people with second-line failure, the corresponding proportions were 79% and 94% respectively. 

Inzaule et al. also reported on drug resistance in East Africa.  They too showed that one in four patients failing second line treatment across Kenya could not be treated effectively with the medicines currently registered in Kenya.

While drug resistance is certainly a threat to the success of ART programmes, it is important to remember that resistance can be minimised by paying close attention to supporting those on treatment to maximize adherence.  Viral load assays need to be cheaper, simpler and more widely available to prevent unnecessary switching.  The results of the recent population-based HIV impact assessments (PHIA) are somewhat reassuring.  In random population-based surveys in Zimbabwe, Zambia and Malawi, 87%-91% of people taking ART had a suppressed viral load.  And in these three countries, the large majority of people are still taking first line treatment and viral load assays are not routinely available.  “Alert but not alarmed” was the message from the WHO press release accompanying their report. 

Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapy.

Svärd J, Mugusi S, Mloka D, Neogi U, Meini G, Mugusi F,Incardona F, Zazzi M, Sönnerborg A. PLoS One. 2017 Jun 5;12(6):e0178942. doi: 10.1371/journal.pone.0178942. eCollection 2017.

Introduction: Antiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered. If failure on first-line ART occurs, a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and boosted lopinavir or atazanavir is recommended.

Materials and methods: Plasma was obtained from subjects with first (n = 174) or second-line (n = 99) treatment failure, as defined by clinical or immunological criteria, as well as from a control group of ART naïve subjects (n = 17) in Dar es Salaam, Tanzania. Amplification of the pol region was performed locally and the amplified DNA fragment was sent to Sweden for sequencing (split genotyping procedure). The therapeutic options after failure were assessed by the genotypic sensitivity score and the EuResist predictive engine. Viral load was quantified in a subset of subjects with second-line failure (n = 52).

Results: The HIV-1 pol region was successfully amplified from 55/174 (32%) and 28/99 (28%) subjects with first- or second-line failure, respectively, and 14/17 (82%) ART-naïve individuals. HIV-1 pol sequence was obtained in 82 of these 97 cases (84.5%). Undetectable or very low (<2.6 log10 copies/10-3 L) viral load explained 19 out of 25 (76%) amplification failures in subjects at second-line ART failure. At first and second line failure, extensive accumulation of NRTI (88% and 73%, respectively) and NNRTI (93% and 73%, respectively) DRMs but a limited number of PI DRMs (11% at second line failure) was observed. First line failure subjects displayed a high degree of cross-resistance to second-generation NNRTIs etravirine (ETR; 51% intermediate and 9% resistant) and rilpivirine (RPV; 12% intermediate and 58% resistant), and to abacavir (ABC; 49% resistant) which is reserved for second line therapy in Tanzania. The predicted probability of success with the best salvage regimen at second-line failure decreased from 93.9% to 78.7% when restricting access to the NRTIs, NNRTIs and PIs currently available in Tanzania compared to when including all approved drugs.

Discussion: The split genotyping procedure is a potential tool to analyse drug resistance in Tanzania but the sensitivity should be evaluated further. The lack of viral load monitoring likely results in a high false positive rate of treatment failures, unnecessary therapy switches and massive accumulation of NRTI and NNRTI mutations. The introduction of regular virological monitoring should be prioritized and integrated with drug resistance studies in resource limited settings.

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Emergence of untreatable, multidrug-resistant HIV-1 in patients failing second-line therapy in Kenya.

Inzaule SC, Hamers RL, Mukui I, Were K, Owiti P, Kwaro D, Rinke de Wit TF, Zeh C. AIDS. 2017 Jun 19;31(10):1495-1498. doi: 10.1097/QAD.0000000000001500.

We performed a countrywide assessment of HIV drug resistance among 123 patients with virological failure on second-line antiretroviral therapy (ART) in Kenya. The percentage of patients harbouring intermediate-to-high-level resistance was 27% for lopinavir-ritonavir, 24% for atazanavir-ritonavir and 7% for darunavir-ritonavir, and 25% had complete loss of activity to all available first and second-line drugs. Overall, one in four patients failing second-line ART have completely exhausted available antiretrovirals in Kenya, highlighting the need for increased access to third-line drugs.

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Africa
Kenya, United Republic of Tanzania
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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.

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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
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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
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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.

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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.

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Africa, Asia, Europe, Northern America
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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.

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Africa
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Non-communicable diseases and co-morbidities – the flip side of successful ART programmes?

Editor’s notes: As the population of people living with HIV grows older and lives longer, the importance of non-communicable diseases is increasing.  Several studies this month explored various aspects of this intersection.

An encouraging study from Spain by Sorigué M et al., analysed the outcomes of patients with advanced stage Hodgkin’s lymphoma, a relatively common cancer both among people living with HIV and the HIV-negative population. The authors showed that, in the era of combined antiretroviral therapy, the complete response rate and ten year survival were not significantly different among people living with HIV (89% and 73%) and HIV negative people (91% and 68%).

Another broadly encouraging study from Ireland by Tinago W et al., followed up 384 people (176 living with HIV) to determine changes over three years in their bone mineral density (BMD).  BMD was somewhat lower in the people living with HIV, despite the group being younger on average.  As expected, BMD gradually fell with increasing age but the rate of bone loss was no different between people living with HIV and HIV negative people.  88% of the people living with HIV were on ART at the start of the study period.  Not having started ART among people living with HIV was associated with lower BMD and people who had started more recently showed the largest declines in BMD.  This suggests (as has previously been shown in cohorts of people living with HIV) that after an initial loss in BMD, the rate of loss stabilizes and is similar to HIV-negative people.  Interestingly, the authors did not show that overall exposure to tenofovir disproxil fumarate (TDF) was particularly associated with greater BMD loss over the course of follow up, despite several previous randomized trials confirming that TDF does cause BMD loss when it is started.

While on the subject of TDF, this month saw two important regulatory trials of tenofovir alafenamide (TAF), sponsored by the manufacturers Gilead Sciences.  630 people living with HIV on treatment with rilpivirine, emtricitabine and TDF whose viral load was supressed, were randomly allocated to remain on the same regimen or to swap the TDF for TAF.  TAF is a pro-drug, that reduces the plasma concentrations of tenofovir and is therefore expected to reduce the renal and bone toxicities associated with TDF while still delivering active drug to the cells where it is needed.  One year later, viral suppression was very similar in the two groups (94%).  There was also no significant difference seen in the side effects over this one year period, with no serious adverse events and 6% vs. 12% having some side effects in the TAF and TDF arms respectively [Orkin C and colleagues].

A related study by DeJesus E et al. with the same design was conducted among people taking efavirenz, emtricitabine and tenofovir, one of the most common first line regimens throughout the world. In this trial the efavirenz was switched to rilpivirine and the TDF to TAF.  875 people living with HIV whose viral load was supressed were randomized and after one year viral suppression was very similar in the two groups (90-92%).  There was also no significant difference seen in the side effects over this one year period, with no serious adverse events and 13% vs. 10% having some side effects in the rilpivirine -TAF and efavirenz-TDF arms respectively.

Returning to co-morbidities and non-communicable diseases, a study by Rodríguez-Arbolí E and colleagues in rural Tanzania has shown that 11.6% of people living with HIV who had not yet started ART had raised blood pressure.  A further 9.6% develop raised blood pressure during follow up, an incidence of 12 per 100 person years. The risk factors for developing hypertension were those well recognized in HIV-negative populations (age, renal disease and being overweight) and not specifically related to HIV infection, ART or immunological status.  The authors recommend integration of non-communicable disease screening and management into HIV care clinics but a larger conclusion might be to improve management of hypertension more generally, as it affects both people living with HIV and people without.

In contrast, a study by Pollack TM et al. from Viet Nam shows that smoking tobacco is associated with a higher viral load among people living with HIV presenting for ART.  As would be expected, other predictors of more advanced HIV disease such as lower CD4 counts and lower BMI and prior TB were all associated with a higher viral load at presentation.  Male sex was also significantly associated with a higher viral load.  The authors point out various other studies from Cameroon and the US that have shown similar and related interactions between smoking tobacco, viral load at presentation or viral load suppression or rebound on ART treatment.  Other studies in the US have not found this association.  One of the challenges is to separate behavioural factors that might be confounders – perhaps people who smoke are more likely to present late.  In this study there was not a clear dose response.  People who smoked more than ten cigarettes per day were actually somewhat less likely in this sample to have a higher viral load than people who smoked 1-10 cigarettes per day, but the numbers were too small to make statistically significant claims.  The authors suggest that oxidative stress and induction of the cytochrome P450 (CYP) pathway could explain the mechanism of smoking-related increased VL among HIV positive individuals.  While the study cannot prove cause and effect, there are already many reasons to promote tobacco cessation among people living with HIV and this may be an additional one.

The D:A:D study is a major prospective cohort that follows more than 49 000 people living with HIV in Europe, Australia and the USA.  Among the cohort, more than 4000 have developed chronic renal impairment.  A study by Ryom L et al. this month examined whether there was improvement, stabilisation or progression of renal impairment in the 2006 individuals who had additional measurements 2-3 years after renal impairment was first noted and explored risk factors for each.  On the one hand, they show that some ARVs (notably TDF and ritonavir-boosted atazanovir) are associated with worse renal outcomes, but on the other hand, they demonstrate that after stopping these nephrotoxic medicines, the kidneys recover or at least do not deteriorate further.  Once again, traditional risk factors (older age, high blood pressure and diabetes) are also important risk factors for the kidneys of people living with HIV.  As the population of people living with HIV gets older and lives longer, HIV care and traditional non-communicable disease management must overlap and coordinate.

HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine and dacarbazine.

Sorigué M, García O, Tapia G, Baptista MJ, Moreno M, Mate JL, Sancho JM, FeliuE, Ribera JM, Navarro JT. AIDS. 2017 Mar 29. doi: 10.1097/QAD.0000000000001487. [Epub ahead of print]

Objective: Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the study was to compare the characteristics, the response with treatment and survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients.

Design and methods: We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD.

Results: A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival 10-year disease-free survival 70% (41-99%) vs. 74% (57-91%), P = 0.907 and overall survival (OS) 10-year OS 73% (95% confidence interval52-94%) vs. 68% (51-85%), P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS.

Conclusion: Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.

Abstract access 

Predictors of longitudinal change in bone mineral density in a cohort of HIV-positive and negative patients.

Tinago W, Cotter AG, Sabin CA, Macken A, Kavanagh E, Brady JJ, McCarthy G,Compston J, Mallon PW; HIV UPBEAT Study Group.225. AIDS. 2017 Mar 13;31(5):643-652. doi: 10.1097/QAD.0000000000001372.

Objective: Although low bone mineral density (BMD) is prevalent in HIV, changes in BMD over time remain unclear. We aimed to compare rates of, and factors associated with, BMD change between HIV-positive and HIV-negative patients.

Methods: In a prospective, 3-year cohort, HIV-positive and HIV-negative patients provided annual demographic and clinical data, fasting bloods, and dual x-ray absorptiometry. Using longitudinal mixed models we compared and determined predictors of rate of change in BMD.

Results: Of 384 study participants (45.8% HIV positive), 120 contributed two and 264 contributed three BMD measurements. Those with HIV were younger [median interquartile range 39 (34-46) vs. 43 (35-50) years; P = 0.04], more often men (61 vs. 46%; P = 0.003), and less likely Caucasian (61 vs. 82%; P < 0.001).Although BMD was lower in those with HIV, BMD declined in both groups, with nonsignificant between-group difference in rate of BMD change over time. Within the HIV group, starting antiretroviral therapy (ART) within 3 months of enrolment was associated with greater BMD decline at all anatomical sites (all P < 0.001). Age more than 30 years, Caucasian ethnicity, and not being on ART during follow-up were associated with greater decline and higher parathyroid hormone associated with a smaller decline in BMD at the femoral neck. We found no association between BMD change and exposure to tenofovir disoproxil fumarate or protease inhibitors.

Conclusion: We observed no difference in rate of BMD decline regardless of HIV status and in HIV-positive patient, having started ART within the previous 3 months was the only factor associated with greater BMD decline at all three sites.

Abstract access 

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study.

Orkin C,  DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Vandercam B, de Wet J, Rockstroh J, Lazzarin A, Rijnders B, Podzamczer D, Thalme A, Stoeckle M, Porter D, Liu HC, Cheng A, Quirk E, SenGupta D, Cao H. Lancet HIV. 2017 Mar 1. pii: S2352-3018(17)30031-0. doi:10.1016/S2352-3018(17)30031-0. [Epub ahead of print]

Background: Tenofovir alafenamide, a tenofovir prodrug, results in 90% lower tenofovir plasma concentrations than does tenofovir disproxil fumarate, thereby minimising bone and renal risks. We investigated the efficacy, safety, and tolerability of switching to a single-tablet regimen containing rilpivirine, emtricitabine, and tenofovir alafenamide compared with remaining on rilpivirine, emtricitabine, and tenofovir disoproxil fumarate.

Methods: In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-1-infected adults were screened and enrolled at 119 hospitals in 11 countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA <50 copies per ml) on rilpivirine, emtricitabine, and tenofovir disoproxil fumarate for at least 6 months before enrolment and had creatinine clearance of at least 50 ml/min. Participants were randomly assigned(1:1) to receive a single-tablet regimen of either rilpivirine (25 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) or to remain on a single-tablet regimen of rilpivirine (25 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), with matching placebo, once daily for 96 weeks. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug and were on the tenofovir disoproxil fumarate regimen before screening were included in primary efficacy analyses. The primary endpoint was the proportion of participants with less than 50 copies per ml of plasma HIV-1 RNA at week 48 (by the US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 8%. This study was registered with clinicaltrials.gov, number NCT01815736.

Findings: Between Jan 26, 2015, and Aug 25, 2015, 630 participants were randomised (316 to the tenofovir alafenamide group and 314 to the tenofovir disoproxil fumarate group). At week 48, 296 (94%) of 316 participants on tenofovir alafenamide and 294 (94%) of 313 on tenofovir disoproxil fumarate had maintained less than 50 copies per ml HIV-1 RNA (difference -0·3%, 95·001% CI-4·2 to 3·7), showing non-inferiority of tenofovir alafenamide to tenofovir disoproxil fumarate. Numbers of adverse events were similar between groups. 20(6%) of 316 participants had study-drug related adverse events in the tenofovir alafenamide group compared with 37 (12%) of 314 in the tenofovir disoproxil fumarate group; none of these were serious.

Interpretation: Switching to rilpivirine, emtricitabine, and tenofovir alafenamide was non-inferior to continuing rilpivirine, emtricitabine, tenofovir disoproxil fumarate in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection.

Abstract access 

Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study.

DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Martorell CT, de Wet J, Stellbrink HJ, Molina JM, Post FA, Valero IP, Porter D, Liu Y, Cheng A, Quirk E, SenGupta D, Cao H. Lancet HIV. 2017 Mar 1. pii: S2352-3018(17)30032-2. doi:10.1016/S2352-3018(17)30032-2. [Epub ahead of print]

Background: Tenofovir alafenamide is a prodrug that reduces tenofovir plasma concentrations by 90% compared with tenofovir disoproxil fumarate, thereby decreasing bone and renal risks. The coformulation of rilpivirine, emtricitabine,and tenofovir alafenamide has recently been approved, and we aimed to investigate the efficacy, safety, and tolerability of switching to this regimen compared with remaining on coformulated efavirenz, emtricitabine, and tenofovir disoproxil fumarate.

Methods: In this randomised, double-blind, placebo-controlled, non-inferiority trial, HIV-1-infected adults were enrolled at 120 hospitals and outpatient clinics in eight countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA <50 copies per mL) on efavirenz, emtricitabine, and tenofovir disoproxil fumarate for at least 6 months before enrolment and had creatinine clearance of at least 50 mL/min. Participants were randomly assigned(1:1) to receive a single-tablet regimen of rilpivirine (25 mg), emtricitabine(200 mg), and tenofovir alafenamide (25 mg) or to continue a single-tablet regimen of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), with matching placebo. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50copies per mL at week 48 (assessed by the US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 8%. This study was registered with ClinicalTrials.gov, number NCT02345226.

Findings: Between Jan 26, 2015, and Aug 27, 2015, 875 participants were randomly assigned and treated (438 with rilpivirine, emtricitabine, and tenofovir alafenamide and 437 with efavirenz, emtricitabine, tenofovir disoproxil fumarate). Viral suppression at week 48 was maintained in 394 (90%) of 438 participants assigned to the tenofovir alafenamide regimen and 402 (92%) of 437 assigned to the tenofovir disoproxil fumarate regimen (difference -2·0%, 95·001% CI -5·9 to 1·8), demonstrating non-inferiority. 56 (13%) of 438 in participants in the rilpivirine, emtricitabine, and tenofovir alafenamide group experienced treatment-related adverse events compared with 45 (10%) of 437 in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group.

Interpretation: Switching to rilpivirine, emtricitabine, and tenofovir alafenamide from efavirenz, emtricitabine, and tenofovir disoproxil fumarate was non-inferior in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection.

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Incidence and risk factors for hypertension among HIV patients in rural Tanzania - A prospective cohort study.

Rodríguez-Arbolí E, Mwamelo K, Kalinjuma AV, Furrer H, Hatz C, Tanner M, Battegay M, Letang E; KIULARCO Study Group. PLoS One. 2017 Mar 8;12(3):e0172089. doi: 10.1371/journal.pone.0172089.eCollection 2017.

Introduction: Scarce data are available on the epidemiology of hypertension among HIV patients in rural sub-Saharan Africa. We explored the prevalence, incidence and risk factors for incident hypertension among patients who were enrolled in a rural HIV cohort in Tanzania.

Methods: Prospective longitudinal study including HIV patients enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2013 and 2015. Non-ART naïve subjects at baseline and pregnant women during follow-up were excluded from the analysis. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg on two consecutive visits. Cox proportional hazards models were used to assess the association of baseline characteristics and incident hypertension.

Results: Among 955 ART-naïve, eligible subjects, 111 (11.6%) were hypertensive at recruitment. Ten women were excluded due to pregnancy. The remaining 834 individuals contributed 7967 person-months to follow-up (median 231 days, IQR 119-421) and 80 (9.6%) of them developed hypertension during a median follow-up of 144 days from time of enrolment into the cohort [incidence rate 120.0 cases/1000 person-years, 95% confidence interval (CI) 97.2-150.0]. ART was started in 630 (75.5%) patients, with a median follow-up on ART of 7 months (IQR 4-14). Cox regression models identified age [adjusted hazard ratio (aHR) 1.34 per 10 years increase, 95% CI 1.07-1.68, p = 0.010], body mass index (aHR per 5 kg/m2 1.45, 95% CI 1.07-1.99, p = 0.018) and estimated glomerular filtration rate (aHR < 60 versus ≥ 60 ml/min/1.73 m2 3.79, 95% CI 1.60-8.99, p = 0.003) as independent risk factors for hypertension development.

Conclusions: The prevalence and incidence of hypertension were high in our cohort. Traditional cardiovascular risk factors predicted incident hypertension, but no association was observed with immunological or ART status. These data support the implementation of routine hypertension screening and integrated management into HIV programmes in rural sub-Saharan Africa.

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Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam.

Pollack TM, Duong HT, Pham TT, Do CD, Colby D. PLoS One. 2017 Mar 7;12(3):e0173534. doi: 10.1371/journal.pone.0173534.eCollection 2017.

High HIV viral load (VL >100 000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100 000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1-10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15-3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75-2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100 000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use among HIV-infected patients.

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Predictors of eGFR progression, stabilisation or improvement after chronic renal impairment in HIV-positive individuals.

Ryom L, Mocroft A, Kirk O, Reiss P, Ross M, Smith C, Moranne O, Morlat P, Fux CA, Sabin C, Phillips A, Law M, Lundgren JD; D:A:D study group. AIDS. 2017 Mar 28. doi: 10.1097/QAD.0000000000001464. [Epub ahead of print]

Objectives: The objectives of this analysis were to investigate predictors of progression, stabilisation or improvement in eGFR after development of chronic renal impairment (CRI) in HIV-positive individuals.

Design: Prospective observational study.

Methods: D:A:D study participants progressing to CRI defined as confirmed, ≥ 3 months apart, eGFR ≤70  mL/min/1.73m were included in the analysis. The median of all eGFRs measured 24-36 months post-CRI was compared to the median eGFR defining CRI, and changes were grouped into: improvement (>+10 mL/min/1.73m), stabilisation (-10 to +10 mL/min/1.73m) and progression (<-10 mL/min/1.73m). Adjusted polynomial regression models assessed odds of better eGFR outcomes after CRI, assuming eGFR improvement is better than stabilisation which in turn is better than progression.

Results: Of 2006 individuals developing CRI, 21% subsequently improved eGFR, 67% stabilised and 12% progressed. Individuals remaining on TDF or boosted atazanavir (ATV/r) 24 months post-CRI had worse eGFR outcomes compared to those unexposed (TDF: 0.47 [0.35-0.63], ATV/r: 0.63 [0.48-0.82]). Individuals off TDF for 12-24 months (0.75 [0.50-1.13]) or off ATV/r for >12 months (1.17 [0.87-1.57]) had similar eGFR outcomes as those unexposed to these ARVs. Older age, hypertension, later date of CRI and diabetes were associated with worse eGFR outcomes.

Conclusion: Current TDF and ATV/r use after a diagnosis of CRI was associated with worse eGFR outcomes. In contrast, TDF and ATV/r discontinuation lead to similar longer-term eGFR outcomes as in those unexposed suggesting these drug-associated eGFR declines may be halted or reversed after their cessation.

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Comorbidity, HIV Treatment
Africa, Asia, Europe, Northern America, Oceania
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