Articles tagged as "HIV transmission"

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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Some key considerations for surveys of key populations

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

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

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

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

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

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

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

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

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

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

Abstract  Full-text [free] access

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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Africa, Asia
Malawi, Philippines, Uganda
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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.

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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.

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

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

Abstract

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

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

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

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

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

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

Abstract  Full-text [free] access

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

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

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

Abstract  Full-text [free] access

 

Africa, Asia, Europe, Northern America, Oceania
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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.

Abstract  Full-text [free] access

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

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

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

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

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

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

Abstract  Full-text [free] access

 

Africa, Asia, Northern America
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