Articles tagged as "phylogenetics"

Most HIV transmission occurs within households or within communities, even among highly mobile fishing communities around Lake Victoria

Editor’s notes: It is well recognized that the fishing communities around Lake Victoria have high HIV prevalence.  Fishermen move around to find the best yield and women who buy and sell fish often meet the boats at different fishing villages and may also trade sex for the best fish to maximize their business. It is therefore, perhaps, surprising that Kiwuwa-Muyingo and colleagues’ study of the phylogenetics of HIV in five distinct fishing communities in Uganda shows that 83% of the transmission events occur in the context of either household or the local community.  Transmission between the communities was less common than expected.  On the other hand, many isolates of HIV could not be linked to another isolate in the study, suggesting that they had been imported into the region, or that their transmission cluster had not been sampled.  A major challenge for molecular epidemiology studies is that limited coverage of the sampling means that unique isolates might have become linked isolates if the sampling had included more of the population.  The authors of this study estimate that they included approximately 44% of all HIV positive individuals in this study cohort, which is similar or better than many phylogenetic studies, but still leaves a lot of room for misclassification biases. A strength of the study was that the authors also included HIV isolates from individuals who had been HIV-negative and followed up over an 18-month period.  Among the 34 transmission clusters, 11 included at least one incident case.  Although the numbers become too small to be confident, they found that in 36% (4) of these 11 clusters, transmission was likely from one incident case to another incident case.  This is an important observation as it highlights the ongoing spread of HIV from recent infection. Transmission of this sort is harder to prevent through the scale up of treatment as it would require people to be tested very regularly, to start treatment before their partner was infected too.  Another interesting observation, again based on limited numbers, is that HIV subtype C was more likely to be involved in transmission clusters than subtype A, which in turn was more commonly in clusters than subtype D.  Subtype C is not so common and presumably imported into these communities, whereas subtypes A and D are the most common subtypes.  We are still in the early days of phylogenetics among African isolates of HIV and many studies have significant limitations, so interpretation needs to be cautious.  Nonetheless, these techniques will increasingly shed light on the complex and sometimes unexpected interactions between individuals, communities, occupations, migration and HIV subtypes.  These insights should help us to focus our HIV prevention and treatment efforts to maximize their impact in the future. 

HIV-1 transmission networks in high risk fishing communities on the shores of Lake Victoria in Uganda: A phylogenetic and epidemiological approach.

Kiwuwa-Muyingo S, Nazziwa J, Ssemwanga D, Ilmonen P, Njai H, Ndembi N, Parry C, Kitandwe PK, Gershim A, Mpendo J, Neilsen L, Seeley J, Seppälä H, Lyagoba F, Kamali A, Kaleebu P. PLoS One. 2017 Oct 12;12(10):e0185818. doi:10.1371/journal.pone.0185818. eCollection 2017.

Background: Fishing communities around Lake Victoria in sub-Saharan Africa have been characterised as a population at high risk of HIV-infection.

Methods: Using data from a cohort of HIV-positive individuals aged 13-49 years, enrolled from 5 fishing communities on Lake Victoria between 2009-2011, we sought to identify factors contributing to the epidemic and to understand the underlying structure of HIV transmission networks. Clinical and socio-demographic data were combined with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic fragments were amplified and sequenced from 283 HIV-1-infected participants. Phylogenetic clusters with ≥2 highly related sequences were defined as transmission clusters. Logistic regression models were used to determine factors associated with clustering.

Results: Altogether, 24% (n = 67/283) of HIV positive individuals with sequences fell within 34 phylogenetically distinct clusters in at least one gene region (either gag or env). Of these, 83% occurred either within households or within community; 8/34 (24%) occurred within household partnerships, and 20/34 (59%) within community. 7/12 couples (58%) within households clustered together. Individuals in clusters with potential recent transmission (11/34) were more likely to be younger 71% (15/21) versus 46% (21/46) in un-clustered individuals and had recently become resident in the community 67% (14/21) vs 48% (22/46). Four of 11 (36%) potential transmission clusters included incident-incident transmissions. Independently, clustering was less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 [95% CI 0.26-1.00]) than A and more likely in those living with an HIV-infected individual in the household (aOR = 6.30 [95% CI 3.40-11.68]).

Conclusions: A large proportion of HIV sexual transmissions occur within house-holds and within communities even in this key mobile population. The findings suggest localized HIV transmissions and hence a potential benefit for the test and treat approach even at a community level, coupled with intensified HIV counselling to identify early infections.

Abstract  Full-text [free] access

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Abstract Full-text [free] access

 

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

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

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

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

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

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

Abstract Full-text [free] access

 

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

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

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

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

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

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

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

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

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

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

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

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

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

Abstract  Full-text [free] access 

 

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

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

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

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Africa
South Africa, Zimbabwe
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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

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Abstract

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

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

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

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

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

Abstract  Full-text [free] access

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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Africa, Asia, Northern America
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Phylogenetics - powerful new tools tied to ethical imperatives for key populations

Editor’s notes: There are now well over half a million HIV isolates that have been sequenced and the data stored in public accessible Genbank.  A systematic review by Hassan AS and colleagues of the methods used to define phylogenetic trees and clusters within them demonstrates the importance of using the correct criteria for the hypothesis being tested. Most articles use the pol sequence, since this is what is sequenced for drug resistance testing.  Most analyses have been done using a phylogenetic approach that uses a probability to assess the likelihood that isolates are clustered, and so depends on the cut-off value chosen.  For example, a well-studied outbreak of HIV among drug users in Finland is clearly linked to an earlier outbreak in Sweden, but because the Finnish isolates were collected later, they had already diverged somewhat from the Swedish ones.  If the threshold was set too high, they would not be recognized to be part of the same outbreak.  However for active transmission chains, a high threshold is needed to avoid falsely linking isolates.  There is no consensus on what methods to use, so caution is needed when comparing different studies.

Mark Wainberg, Professor of Medicine and of Microbiology at McGill University and a giant of Canadian HIV science, passed away this month.  So, as a tribute to his work, we have chosen a study from the McGill AIDS Centre by Brenner BG and colleagues.  The team used phylogenetic analysis to classify pre-treatment HIV isolates from 3901 men who have sex with men in Quebec according to the likelihood of being an acute or recent infection and the likelihood of clustering with other isolates.  Over the period from 2002-2015, a larger and larger proportion of the infections in this population could be linked to larger clusters, particularly involving younger men and men with recent infection, many of whom did not know their HIV status.  At least 40% of the onward spread of the epidemic in Quebec can be ascribed to just thirty clusters, varying in size from 20–140 individuals.

Using phylogenetics to understand transmission patterns requires careful attention to ethics, confidentiality and stigmatization.  A study in South Korea by Ahn MY and colleagues aimed to define the risk factors for clustering within clusters among 143 people living with HIV in four cities.  In eight out of the nine clusters identified participants did not report the same risk factors. Clusters were small, eight pairs and one quartet.  In the two tightest clusters, where the isolates were indistinguishable on the sequences examined, one man stated that he had sex with women, but the paired isolate came from another man and in the other pair, both men chose not to disclose their risk factors.  With small studies where information can sometimes be inferred even when not disclosed, it is perhaps not surprising that more than half the participants chose not to report their risk factors.

Other phylogenetic studies this month have explored the evolution of HIV recombination and the spread of different clades in communities in North-Eastern Brazil [Delatorre E et al.] and China.  In the North-Eastern states of Brazil, 72% of HIV isolates were subtype B, but rare subtypes such as D (1%) and CRF02_AG (1%) appear to be spreading within the population rather than being introduced from outside. In China studies from Sichuan [Wang Y et al.], Yunnan [Li Y and colleagues] and Zhejiang [Wang H et al.] have shown new recombinant forms of HIV with elements that suggest that viruses from different countries in the region have combined.  The widening diversity of HIV brings challenges for vaccine development, and potentially for HIV assays, such as those for recent infection that may differ in their sensitivity and specificity between different sub-types.  Understanding the migration of people and their viruses could be useful for providing better services, but careful attention to messaging will be needed to prevent such data from being used to discriminate further against migrants.

The final phylogenetic paper this month also comes from China, where Hao M and colleagues reported a study of students living with HIV in Beijing. The study demonstrated that transmitted drug resistance is still low in this setting, with just 0.8% of 237 students having virus that was resistant to non-nucleoside reverse transcriptase inhibitors that form part of the backbone of first line treatment in China.  A further 1.3% has resistance to protease inhibitors that are used in second line treatment.

Defining HIV-1 transmission clusters based on sequence data: a systematic review and perspectives.

Hassan AS, Pybus OG, Sanders EJ, Albert J, Esbjörnsson J. AIDS. 2017 Mar 28. doi: 10.1097/QAD.0000000000001470. [Epub ahead of print]

Understanding HIV-1 transmission dynamics is relevant to both screening and intervention strategies of HIV-1 infection. Commonly, HIV-1 transmission chains are determined based on sequence similarity assessed either directly from a sequence alignment or by inferring a phylogenetic tree. This review is aimed at both nonexperts interested in understanding and interpreting studies of HIV-1transmission, and experts interested in finding the most appropriate cluster definition for a specific dataset and research question. We start by introducing the concepts and methodologies of how HIV-1 transmission clusters usually have been defined. We then present the results of a systematic review of 105 HIV-1 molecular epidemiology studies summarizing the most popular methods and definitions in the literature. Finally, we offer our perspectives on how HIV-1 transmission clusters can be defined and provide some guidance based on examples from real life datasets.

Abstract access 

Large cluster outbreaks sustain the HIV epidemic among MSM in Quebec.

Brenner BG, Ibanescu RI, Hardy I, Stephens D, Otis J, Moodie E, Grossman Z,Vandamme AM, Roger M, Wainberg MA; and the Montreal PHI, SPOT cohorts. AIDS. 2017 Mar 13;31(5):707-717. doi: 10.1097/QAD.0000000000001383.

Objective: HIV-1 epidemics among MSM remain unchecked despite advances in treatment and prevention paradigms. This study combined viral phylogenetic and behavioural risk data to better understand underlying factors governing the temporal growth of the HIV epidemic among MSM in Quebec (2002-2015).

Methods: Phylogenetic analysis of pol sequences was used to deduce HIV-1transmission dynamics (cluster size, size distribution and growth rate) in first genotypes of treatment-naïve MSM (2002-2015, n = 3901). Low sequence diversity of first genotypes (0-0.44% mixed base calls) was used as an indication of early-stage infection. Behavioural risk data were obtained from the Montreal rapid testing site and primary HIV-1-infection cohorts.

Results: Phylogenetic analyses uncovered high proportion of clustering of new MSM infections. Overall, 27, 45, 48, 53 and 57% of first genotypes within one (singleton, n = 1359), 2-4 (n = 692), 5-9 (n = 367), 10-19 (n = 405) and 20+ (n = 1277) cluster size groups were early infections (<0.44% diversity). Thirty viruses within large 20+ clusters disproportionately fuelled the epidemic, representing 13, 25 and 42% of infections, first genotyped in 2004-2007 (n = 1314), 2008-2011 (n = 1356) and 2012-2015 (n = 1033), respectively. Of note, 35, 21 and 14% of MSM belonging to 20+, 2-19 and one (singleton) cluster groups were under 30 years of age, respectively. Half of persons seen at the rapid testing site (2009-2011, n = 1781) were untested in the prior year. Poor testing propensity was associated with fewer reported partnerships.

Conclusion: Addressing the heterogeneity in transmission dynamics among HIV-1-infected MSM populations may help guide testing, treatment and prevention strategies.

Abstract access 

HIV-1 transmission networks across South Korea.

Ahn MY, Wertheim JO, Kim WJ, Kim SW, Lee JS, Ann HW, Jeon Y, Ahn JY, Song JE, Oh DH, Kim YC, Kim EJ), Jung IY, Kim MH, Jeong W, Jeong SJ, Ku NS, Kim JM, Smith DM, Choi JY. AIDS Res Hum Retroviruses. 2017 Mar 27. doi: 10.1089/aid.2016.0212. [Epub ahead of print]

Molecular epidemiology can help clarify the properties and dynamics of HIV-1 transmission networks in both global and regional scales. We studied 143 HIV-1-infected individuals recruited from four medical centers of three cities in South Korea between April 2013 and May 2014. HIV-1 env V3 sequence data were generated (337-793 bp) and analyzed using a pairwise distance-based clustering approach to infer putative transmission networks. Participants whose viruses were ≤2.0% divergent according to Tamura-Nei 93 genetic distance were defined as clustering. We collected demographic, risk, and clinical data and analyzed these data in relation to clustering. Among 143 participants, we identified nine putative transmission clusters of different sizes (range 2-4 participants). The reported risk factor of participants were concordant in only one network involving two participants, that is, both individuals reported homosexual sex as their risk factor. The participants in the other eight networks did not report concordant risk factors, although they were phylogenetically linked. About half of the participants refused to report their risk factor. Overall, molecular epidemiology provides more information to understand local transmission networks and the risks associated with these networks.

Abstract access 

HIV-1 Genetic diversity in northeastern Brazil: high prevalence of non-B subtypes.

Delatorre E, Couto-Fernandez JC, Bello G.AIDS Res Hum Retroviruses. 2017 Mar 22. doi: 10.1089/AID.2017.0045. [Epub ahead of print]

The Northeastern Brazilian region has experienced a constant increase in the number of newly reported AIDS cases over the last decade, but the genetic diversity of HIV-1 strains currently disseminated in this region remains poorly explored. HIV-1 pol sequences were obtained from 140 patients followed at outpatient clinics from four Northeastern Brazilian states (Alagoas, Bahia, Ceará and Piauí) between 2014 and 2015. Subtype B was the most prevalent HIV-1 clade (72%) detected in the Northeastern region, followed by subtypes F1 (6%), C (5%) and D (1%). The remaining strains (16%) displayed a recombinant structure and were classified as: BF1 (11%), BC (4%), BCF1 (1%) and CRF02_AG-like (1%). The 20 HIV-1 BF1 and BC recombinant sequences detected were distributed among 11 lineages classified as: CRF28/29_BF-like (n = 5), CRF39_BF-like (n = 1), URFs_BF (n = 9) and URFs_BC (n = 5). Non-B subtypes were detected in all Northeastern Brazilian states, but with variable prevalence, ranging from 16% in Ceará to 55% in Alagoas. Phylogenetics analyses support that subtype D and CRF02_AG strains detected in the Northeastern region resulted from the expansion of autochthonous transmission networks, rather than from exogenous introductions from other countries. These results reveal that HIV-1 epidemic spreading in the Northeastern Brazilian region is comprised by multiple subtypes and recombinant strains and that the molecular epidemiologic pattern in this Brazilian region is much more complex than originally estimated.

Abstract access 

Identification of a novel HIV type 1 CRF01_AE/B'/C recombinant isolate in Sichuan, China.

Wang Y, Kong D, Xu W, Li F, Liang S, Feng Y, Zhang F, Shao Y, Ma L. AIDS Res Hum Retroviruses. 2017 Mar 13. doi: 10.1089/aid.2017.0002. [Epub ahead of print]

We report in this study a novel HIV-1 unique recombinant virus (XC2014EU01) isolated from an HIV-positive man who infected through heterosexual sex in Sichuan, China. The near full-length genome analyses showed that XC2014EU01 harbored one subtype B segment in pol region and two subtype C segments in gag-pol region in a CRF01_AE backbone. The unique mosaic structure was distinctly different from the other CRF01_AE/B'/C recombinant forms reported. Phylogenetic tree analyses revealed that the subtype B region originated from a Thailand subtype B' lineage, the subtype C regions were from an India C lineage, and the backbone was from CRF01_AE. XC2014EU01 was still identified as CCR5-tropic, and plasma of XC2014EU01 infected person had the media neutralizing activity. The emergence of XC2014EU01 may increase the complexity of the HIV-1 epidemic among high-risk populations and the difficulty of vaccine research and development.

Abstract access 

Identification of a novel HIV type 1 circulating recombinant form (CRF86_BC) among heterosexuals in Yunnan, China.

Li Y, Miao J, Miao Z, Song Y, Wen M, Zhang Y, Guo S, Zhao Y, Feng Y, Xia X. AIDS Res Hum Retroviruses. 2017 Mar;33(3):279-283. doi: 10.1089/AID.2016.0188. Epub 2016 Oct 18.

In recent years, multiple circulating recombinant forms (CRFs) and unique recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been described in Yunnan, China. Here, we identified a novel HIV-1 CRF (CRF86_BC) isolated from three heterosexuals with no obvious epidemiologic linkage in western Yunnan (Baoshan prefecture) in China. CRF86_BC had a subtype C backbone with four subtype B fragments inserted into the pol, vpr, vpu, env, and nef gene regions, respectively. Furthermore, subregion tree analysis revealed that subtype C backbone originated from an Indian C lineage and subtype B segment inserted was from a Thai B lineage. They are different from previously documented B/C forms in its distinct backbone, inserted fragment size, and break points. This highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in this region.

Abstract access 

Near full-length genomic characterization of a novel HIV-1 unique recombinant (CRF55_01B/CRF07_BC) from a Malaysian immigrant worker in Zhejiang, China.

Wang H, Luo P, Zhu H, Wang N, Hu J, Mo Q, Yang Z, Feng Y. AIDS Res Hum Retroviruses. 2017 Mar;33(3):275-278.doi: 10.1089/AID.2016.0100. Epub 2016 Aug 17.

Recombinant forms contribute substantially to the genetic diversity of human immunodeficiency virus type 1 (HIV-1). Here we report a novel HIV-1 recombinant detected from a comprehensive HIV-1 molecular epidemiologic study among cross-border populations in China. Near full-length genome (NFLG) phylogenetic analysis showed that the novel HIV-1 recombinant ZJCIQ15005, which was isolated from a Malaysian immigrant worker in Zhejiang, China, clustered with CRF55_01B reference sequences but set up a distinct branch. Recombinant analysis showed that the NFLG of ZJCIQ15005 composed of CRF55_01B (as the backbone) and CRF07_BC,with 12 recombinant break points observed in the pol, vif, vpr, tat, rev, env,nef, and 3'LTR regions. This is the first detection of a novel HIV-1 recombinant (CRF55_01B/CRF07_BC) in immigrant workers in China. The emergence of this recombinant may increase the complexity of the HIV-1 epidemic in China and suggests the importance of continuous surveillance of the dynamic changes of HIV-1.

Abstract access 

Low rates of transmitted drug resistances among treatment-naive HIV-1 infected students in Beijing, China.

Hao M, Wang J, Xin R, Li X, Hao Y, Chen J, Ye J, Wang Y, He X, Huang C, Lu H. AIDS Res Hum Retroviruses. 2017 Mar 22. doi: 10.1089/AID.2017.0053. [Epub ahead of print]

Beijing has seen a rising epidemic of HIV among students. However, little information was known about the molecular epidemiologic data among HIV-infected students. In this study, the diversity and the prevalence of TDR in pol sequences deriving from 237 HIV-infected students were analyzed. TDR mutations were found in 5 MSM among students. The overall prevalence of TDR in students was 2.1%, comprised of 1.3% to protease inhibitors and 0.8 % to non-nucleoside reverse transcriptase inhibitors. Our finding indicates a low-level prevalence of TDR mutations among students in Beijing.

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Asia, Latin America, Northern America
Brazil, Canada, China, Republic of Korea
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