Search

BackgroundScale-up of oral pre-exposure prophylaxis (PrEP) for HIV prevention in Uganda began with serodiscordant couples (SDC) and has expanded to other most at-risk populations (MARPs). We explored knowledge, acceptability, barriers and facilitators of PrEP use among potential PrEP users in four MARPs (SDC; men who have sex with men [MSM]; female sex workers [FSW], and fisher folk).MethodsWe administered quantitative surveys to potential PrEP users in multiple settings in Central Uganda at baseline and approximately 9 months after healthcare worker (HCW) training on PrEP.ResultsThe survey was completed by 250 potential PrEP users at baseline and 125 after HCW training; 55 completed both surveys. For these 250 participants, mean age was 28.5 years (SD 6.9), 47% were male and 6% were transgender women, with approximately even distribution across MARPs and recruitment locations (urban, peri-urban, and rural). Most (65%) had not heard about PrEP. After HCW training, 24% of those sampled were aware of PrEP, and the proportion of those who accurately described PrEP as "antiretrovirals to be used before HIV exposure" increased from 54% in the baseline survey to 74% in the second survey (pConclusionsInitial awareness of PrEP was low, but PrEP knowledge and interest increased among diverse MARPs after HCW training. Demand creation and HCW training will be critical for increasing PrEP awareness among key populations, with support to overcome barriers to PrEP use. These findings should encourage the acceleration of PrEP rollout in Uganda.

Background Health care providers usually focus on index HIV-infected patients and seldom obtain information from their partners. We aimed to determine HIV-preventative measures among couples, the prevalence of HIV infection, and treatment outcomes of partners. Methods This cross-sectional study was conducted in two hospital settings, a university hospital in Bangkok and a general hospital in northeastern Thailand, from January 2011-October 2015. Factors associated with serodiscordant relationships were determined by logistic regression. Results A total of 393 couples were enrolled for analysis; 156 (39.7%) were serodiscordant. The median relationship duration of serodiscordant couples was shorter than that of seroconcordant couples (6.4 years vs 11.6 years, p < 0.001). Of 237 HIV-infected partners, 17.7% had AIDS-defining illness, the median nadir CD4 count (interquartile range) was 240 (96–427) cells/mm3, 83.5% received antiretroviral therapy (ART), 98.3% had adherence > 95%, 90.3% had undetectable HIV RNA, and 22.9% had a prior history of treatment failure. There was no significant difference in condom usage in the prior 30 days between serodiscordant and seroconcordant couples. Factors of index HIV-infected patients associated with serodiscordant relationships were younger age (odds ratio [OR] 1.04 per 5 years; 95% confidence interval [CI] 1.01–1.06), receiving care at the general hospital (OR 1.73; 95% CI 1.08–2.78), a shorter duration of relationship (OR 1.04 per year; 95% CI 1.01–1.07), a higher nadir CD4 count (OR 1.06 per 50 cells/mm3; 95% CI 1.1–1.13), and not receiving a protease inhibitor-based regimen (OR 2.04; 95% CI 1.06–3.96). Conclusions A high number of serodiscordant couples was determined. Partners’ information should be retrieved as a holistic approach. Interventions for minimizing HIV transmission within serodiscordant couples should be evaluated and implemented.

Whereas the number of people newly infected by HIV is continuing to decline globally, the epidemic continues to expand in many parts of the world. As the HIV/AIDS epidemic has matured in many countries, it is believed that the proportion of new infections occurring within couples has risen. Across countries, including Mozambique, a sizeable proportion of couples with HIV infection are discordant. A serodiscordant couple is a couple in which one partner has tested positive for HIV and the other has not. To describe the HIV serodiscordance among couples, a variety of association measures can be used. In this paper, we propose the serodiscordance measure (SDM) as a new alternative measure. Focus is on the specification of flexible marginal and random effects models for multivariate correlated binary data together with a full-likelihood estimation method, to adequately and directly describe the measure of interest. Fitting joint models allows examining the effects of different risk factors and other covariates on the probability to be HIV positive for each member within a couple, and estimating common effects for both probabilities more efficiently, while accounting for the association between their infection status. Moreover, the interpretation of the proposed association parameter SDM is more direct and relevant and effects of covariates can be studied as well. Results show that the HIV prevalence for the province where a couple was located as well as the union number for the woman within a couple are factors associated with HIV serodiscordance. These findings are important for the Mozambican public health policy makers to design national prevention plans, which include policies to stimulate regular HIV testing for couples as well as adolescents and young adults, prior to getting married or living together as a couple. Flemish Interuniversity Council (VLIR-UOS) in collaboration with Eduardo Mondlane University (UEM) through the DESAFIO Program provided financial support. This study was only possible thanks to the financial support of the Flemish Interuniversity Council (VLIR-UOS) in collaboration with Eduardo Mondlane University (UEM) through the DESAFIO Program. The authors would also like to acknowledge the support given by the Mozambican Health Ministry (MISAU) and Demography Health Survey (DHS) Program for providing the INSIDA survey data. The authors would also like to thank the editors and the reviewers for their interesting and helpful comments and suggestions.

Background An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. Methods A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. Results The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P

BackgroundHIV-1-discordant couples that remain discordant despite repeated exposure may differ from the general population in their distribution of transmission risk factors, including low plasma viral load (PVL) in the infected partner even in the absence of antiretroviral therapy (ART).MethodsWe followed two cohorts of HIV-1-infected Kenyan women: females in discordant couples (FDC) and female sex workers (FSW). We compared the distribution of undetectable (ResultsWe evaluated 296 FDC and 220 FSW. At baseline, FDC were more likely to have undetectable (RR = 6.94, bootstrap 95% CI: 3.47, 20.81) and low PVL (RR = 3.53, bootstrap 95% CI: 2.57, 5.65) than FSW. Similarly, both repeat undetectable PVL (RR = 9.36, bootstrap 95% CI: 6.04, 10.97) and repeat low (RR = 4.99, bootstrap 95% CI: 2.33, 14.04) PVL were more likely among FDC than FSW during follow-up.DiscussionWe observed higher prevalence of viral control in FDC compared to FSW in the absence of ART, suggesting potentially higher prevalence of biological HIV resistance factors among discordant couples.

Author(s): Gnatienko, Natalia; Wagman, Jennifer A; Cheng, Debbie M; Bazzi, Angela R; Raj, Anita; Blokhina, Elena; Toussova, Olga; Forman, Leah S; Lioznov, Dmitry; Bridden, Carly; Sullivan, Meg; Bryant, Kendall; Samet, Jeffrey H; Tsui, Judith I | Abstract: ObjectiveTo describe the frequency of being partnered and having an HIV-negative partner, and whether this differed by gender, among a cohort of persons living with HIV (PLWH) who have ever injected drugs; to describe awareness of HIV pre-exposure prophylaxis (PrEP) and perceived partner interest in PrEP.SettingSecondary analyses of an observational cohort study of PLWH who have ever injected drugs in St. Petersburg, Russia.MethodsPrimary outcomes were 1) being partnered and 2) being in a serodiscordant partnership. The main independent variable was gender. Multivariable GEE logistic regression models were fit for binary outcomes, adjusted for age, income, education, and recent opioid use. Descriptive analyses were performed for partners' HIV status, substance use, sex risk behaviors, and awareness of PrEP for a subset of participants.ResultsAt baseline, 50% (147/296) reported being in a partnership, and of those, 35% were in a serodiscordant partnership. After adjustment, women had significantly higher odds of being partnered compared to men (aOR = 3.12; 95% CI: 1.77, 5.51), but there were no significant gender differences in the odds of being in a serodiscordant partnership (aOR = 0.58; 95% CI: 0.27, 1.24). Among a sub-sample of participants queried (n = 56), 25% were aware of PrEP for prevention of sexual HIV transmission and 14% for prevention of injection-related transmission.ConclusionAlthough half of our sample were partnered and one third of these partnerships were serodiscordant, PrEP awareness was low. Substantial opportunities for HIV prevention exist among PLWH who have ever injected drugs in Russia and their HIV-negative partners. Given the high proportion of HIV-negative partners among this ART-naive sample, efforts to address the associated inherent risks, such as couples-based interventions, are needed to increase condom use, PrEP awareness, or uptake of other HIV-prevention modalities (e.g., ART for the HIV-positive partner).

Background Serostatus disclosure may facilitate decreased HIV transmission between serodiscordant partners by raising risk awareness and heightening the need for prevention. For women living with HIV (WLWH), the decision to disclose may be influenced by culturally determined, community-level stigma and norms. Understanding the impact of community HIV stigma and gender norms on disclosure among WLWH in different countries may inform intervention development. Methods HPTN063 was a longitudinal, observational study of sexually active HIV-infected individuals, including heterosexual women, in care in Zambia, Thailand and Brazil. At baseline, a questionnaire measuring community HIV stigma and gender norms, anticipated stigma, demographic, partner/relationship characteristics, and intimate partner violence was administered. Longitudinal HIV disclosure to sexual partners was determined via audio-computer assisted self-interview (ACASI) at the baseline and quarterly during the one year following up. Logistic regression was conducted to identify the predictors of disclosure. Results Almost half (45%) of women living with HIV acknowledged perceived community HIV stigma (the belief that in their community HIV infection among women is associated with sex work and multiple sexual partners). Many women (42.9%) also acknowledged perceived community gender norms (the belief that traditional gender norms such as submissiveness to husbands/male sexual partners is necessary and that social status is lost if one does not procreate). HIV disclosure to current sex partners was reported by 67% of women. In multivariate analysis, among all women, those who were older [OR 0.16, 95%CI(0.06,0.48)], reported symptoms of severe depression [OR 0.53, 95%CI(0.31, 0.90)], endorsed anticipated stigma [OR 0.30, 95%CI(0.18, 0.50)], and were unmarried [OR 0.43, 95%CI(0.26,0.71)] were less likely to disclose to current partners. In an analysis stratified by marital status and cohabitation, unmarried [OR 0.41, 95%CI(0.20,0.82)] and non-cohabiting women [OR 0.31, 95%CI(0.13,0.73)] who perceived community HIV stigma were less likely to disclose to their sex partners. Conclusions Perceived community level HIV stigma, along with individual level factors such as anticipated stigma, depressive symptoms, and older age, predict non-disclosure of HIV status to sexual partners among WLWH in diverse geographic settings. Interventions to promote disclosure among women in serodiscordant relationships should incorporate community-level interventions to reduce stigma and promote gender equality.

IntroductionAttempts to conceive and pregnancy may increase HIV transmission to sex partners and infants. Our study evaluated the association between fertility intentions and HIV acquisition among Zambian HIV-serodiscordant couples.MethodsWe collected demographic, behavioral, clinical exposures, and data on fertility intentions in a cohort of HIV-serodiscordant couples in Lusaka, Zambia from 2005 to 2012. We evaluated factors associated with fertility intentions stratified by gender using multivariable logistic regression. Multivariable Cox proportional hazard models were used to evaluate the associations between fertility intentions and HIV acquisition controlling for a priori confounders and covariates that substantially (>10%) changed the effect estimates in univariate analyses.ResultsAmong 1,029 serodiscordant couples, 311 agreed that they wanted children in the future (30%), 368 agreed they did not want children (36%), and 344 couples disagreed about having children (34%), with men more likely than women to want children. Women wanting child(ren) was associated with increased odds of baseline pregnancy (adjusted odds ratio [aOR] = 4.80 (95% confidence interval [CI] = 2.93, 7.85)), fewer previous pregnancies (aOR = 0.85 per additional pregnancy (95% CI = 0.78, 0.93)), and partner fertility intention (aOR = 2.89 (95% CI = 2.14, 3.91)) adjusting for woman's age, literacy, years cohabiting and HIV status. Men wanting child(ren) was associated with younger age (aOR = 0.96 per year (95% CI = 0.93, 0.99)), fewer years cohabiting (aOR = 0.95 (95% CI = 0.92, 0.98)), number of previous partners' pregnancies (aOR = 0.90 (95% CI = 0.82, 0.98)), and partner fertility intention (aOR = 3.00 (95% CI = 2.21, 4.07)) adjusting for partner's age, literacy, HIV status and partner's baseline pregnancy. In adjusted survival analyses, HIV-negative women were more likely to seroconvert if they themselves wanted children (aHR = 2.36 (95% CI = 1.41, 3.96)) vs. did not want children, or if their partner wanted children (aHR = 2.34 (95% CI = 1.33, 4.11)) vs. did not want children, or if the couple agreed that they wanted children (aHR = 2.08 (95% CI = 1.01, 4.30)), adjusting for women's age, women's literacy, previous pregnancies and time in study. HIV-negative men were more likely to seroconvert if their female partner wanted a child in the next 12-months (aHR = 1.94 (95% CI = 1.02, 3.68)) vs. did not want children, and when both partners wanted children (aHR = 2.02 (CI = 1.09, 3.73)) vs. they did not want children, adjusting for men's age and literacy, couple income, number of live children, male circumcision status and time in study.ConclusionWomen had increased risk of HIV acquisition if they and/or their partner wanted a child, while men had increased risk of HIV acquisition when their partner or if both partners agreed that they wanted children. Safer-conception interventions are needed to protect HIV uninfected women and men from HIV acquisition in HIV-serodiscordant couples who want children.

Background Sexual networks may place U.S. Black men who have sex with men (MSM) at increased HIV risk. Methods Self-reported egocentric sexual network data from the prior six months were collected from 1,349 community-recruited Black MSM in HPTN 061, a multi-component HIV prevention intervention feasibility study. Sexual network composition, size, and density (extent to which members are having sex with one another) were compared by self-reported HIV serostatus and age of the men. GEE models assessed network and other factors associated with having a Black sex partner, having a partner with at least two age category difference (age difference between participant and partner of at least two age group categories), and having serodiscordant/serostatus unknown unprotected anal/vaginal intercourse (SDUI) in the last six months. Results Over half had exclusively Black partners in the last six months, 46% had a partner of at least two age category difference, 87% had ≤5 partners. Nearly 90% had sex partners who were also part of their social networks. Among HIV-negative men, not having anonymous/exchange/ trade partners and lower density were associated with having a Black partner; larger sexual network size and having non-primary partners were associated with having a partner with at least two age category difference; and having anonymous/exchange/ trade partners was associated with SDUI. Among HIV-positive men, not having non-primary partners was associated with having a Black partner; no sexual network characteristics were associated with having a partner with at least two age category difference and SDUI. Conclusions Black MSM sexual networks were relatively small and often overlapped with the social networks. Sexual risk was associated with having non-primary partners and larger network size. Network interventions that engage the social networks of Black MSM, such as interventions utilizing peer influence, should be developed to address stable partnerships, number of partners, and serostatus disclosure.

Introduction: Little is known about the state of HIV transmission among married couples in Vietnam. This study aims to clarify HIV serostatus in this group and elucidate risk factors for intra-marital HIV transmission. Methods: In 2012, we enrolled a group of HIV-positive married men registered at the HIV outpatient clinic of a referral hospital in northern Vietnam, along with their wives. Sociodemographic, behavioural and clinical data were collected from men and wives. HIV serodiscordant couples were followed until March 2014 to determine seroconversion rate. A phylogenetic analysis was performed based on env V3 sequence to detail cluster formation among men. Results: Of the 163 HIV-positive men enrolled in the study, 101 (62.0%) had wives testing HIV-negative. Half ofmen reported injecting drug use (IDU) as a likely transmission route. Couples reported a high incidence of unprotected sexual intercourse prior to diagnosis; the median (inter quartile range) was 4 (4-8) times per month. Only 17 couples (10.4%) reported using condoms during at least half these instances. Multivariable analysis revealed IDU history among men was independently associated with HIV-negative wives (adjusted OR 0.31; 95%CI 0.10-0.95, p=0.041). Phylogenetic analysis of 80 samples indicated CRF01-AE. Of these, 69 (86.3%) clustered with IDU-associated viruses from Vietnam. No HIV seroconversion was identified during a follow-up of 61 serodiscordant couples, with 126.5 person-years of observation during which HIV-infectedmen were on antiretroviral drug therapy (ART). Conclusion: High HIV serodiscordance was observed among HIV-affected married couples in northern Vietnam. A large number of at-risk wives therefore remain HIV-negative and can be protected with measures including proper use of ART if couples are made aware of the serodiscordance through screening., PLOS ONE, 10(4), e0125299; 2015

Author(s): Heffron, Renee; Cohen, Craig R; Ngure, Kenneth; Bukusi, Elizabeth; Were, Edwin; Kiarie, James; Mugo, Nelly; Celum, Connie; Baeten, Jared M; Partners PrEP Study, the Partners in Prevention HSV/HIV Transmission Study, and the Partners Demonstration Project Teams | Abstract: IntroductionHIV-1 prevention programs targeting HIV-1 serodiscordant couples need to identify couples that are likely to become pregnant to facilitate discussions about methods to minimize HIV-1 risk during pregnancy attempts (i.e. safer conception) or effective contraception when pregnancy is unintended. A clinical prediction tool could be used to identify HIV-1 serodiscordant couples with a high likelihood of pregnancy within one year.MethodsUsing standardized clinical prediction methods, we developed and validated a tool to identify heterosexual East African HIV-1 serodiscordant couples with an increased likelihood of becoming pregnant in the next year. Datasets were from three prospectively followed cohorts, including nearly 7,000 couples from Kenya and Uganda participating in HIV-1 prevention trials and delivery projects.ResultsThe final score encompassed the age of the woman, woman's number of children living, partnership duration, having had condomless sex in the past month, and non-use of an effective contraceptive. The area under the curve (AUC) for the probability of the score to correctly predict pregnancy was 0.74 (95% CI 0.72-0.76). Scores ≥ 7 predicted a pregnancy incidence of g17% per year and captured 78% of the pregnancies. Internal and external validation confirmed the predictive ability of the score.DiscussionA pregnancy likelihood score encompassing basic demographic, clinical and behavioral factors defined African HIV-1 serodiscordant couples with high one-year pregnancy incidence rates. This tool could be used to engage African HIV-1 serodiscordant couples in counseling discussions about fertility intentions in order to offer services for safer conception or contraception that align with their reproductive goals.

Many HIV serodiscordant couples have a strong desire to have their own biological children. Natural conception may be the only choice in some resource limited settings but data about natural conception is limited. Here, we reported our findings of natural conception in HIV serodiscordant couples. Between January 2008 and June 2014, we retrospectively collected data on 91 HIV serodiscordant couples presenting to Beijing Youan Hospital with childbearing desires. HIV counseling, effective ART on HIV infected partners, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) in negative female partners and timed intercourse were used to maximally reduce the risk of HIV transmission. Of the 91 HIV serodiscordant couples, 43 were positive in male partners and 48 were positive in female partners. There were 196 unprotected vaginal intercourses, 100 natural conception and 97 newborns. There were no cases of HIV seroconversion in uninfected sexual partners. Natural conception may be an acceptable option in HIV-serodiscordant couples in resource limited settings if HIV-positive individuals have undetectable viremia on HAART, combined with HIV counseling, PrEP, PEP and timed intercourse.

Background Sustained viral suppression through ART reduces sexual HIV transmission risk, but may require routine access to reliable and effective medical care which may be difficult to obtain in resource constrained areas. We investigated the roles of patient load and travel distance to HIV care clinic on transmission risk in HIV serodiscordant couples in Henan Province, China. Methods Cox proportional hazard models were used to compare HIV transmission events across couples living near, medium, or farther distances from their assigned HIV care clinics, as well as those attending clinics where clinicians bore high versus low patient loads. Results Most (84·4%) of the 3695 serodiscordant couples lived within 10 kilometers of their assigned HIV clinic, and most (73·5%) attended clinics with patient-to-provider ratios of at least 100:1. In adjusted Cox models, attending clinics where clinicians bore average patient loads of 100 or more elevated HIV transmission risk (aHR, 1·50, 95% CI, 1·00–4·84), an effect amplified in village tier clinics (aHR = 1·55; 95% CI, 1·23–6·78). Travel distance was associated with HIV transmission only after stratification; traveling medium distances to village clinics (5-10km) increased transmission risk (aHR = 1·83, 95% CI, 1·04–3·21) whereas traveling longer distances to township or county level clinics lowered transmission risk (aHR = 0·10, 95% CI, 0·01–0·75). Conclusion Higher patient loads at HIV clinics was associated with risk of HIV transmission in our population, particularly at village level clinics. Farther travel distance had divergent effects based on clinic tier, suggesting unique mechanisms operating across levels of resource availability. The resource intensity of long-term HIV treatment may place significant strains on small rural clinics, for which investments in additional support staff or time-saving tools such as point-of-care laboratory testing may bring about impactful change in treatment outcomes.

Objective To estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa. Methods We incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter. Results We estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively – a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples. Conclusion After a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.

BACKGROUND: Consistent and correct condom use and suppressive antiretroviral therapy for the infected partner are two of the primary strategies recommended for prevention of heterosexual HIV transmission in serodiscordant couples today. The applied effectiveness of treatment as a prevention strategy in China is still under investigation, and much less is known about its effects in the presence of other prevention strategies such as consistent condom use. METHODS: We conducted a systematic search in PubMed and three Chinese language databases to identify relevant articles for the estimation of relative effectiveness of a) consistent condom use and b) ART use by index partners for preventing HIV transmission in serodiscordant couples. We also estimated the prevention effectiveness of ART stratified by condom use level and the prevention effectiveness of consistent condom use stratified by ART use level. RESULTS: Pooled results from the eleven eligible studies found a pooled HIV seroconversion incidence of 0.92 cases per 100 person years (PY) among HIV-negative spouses whose index partners were taking ART versus 2.45 cases per 100 PY in untreated couples. The IRR comparing seroconversion in couples where the index-partner was on ART versus not on ART was 0.47 (95%CI: 0.43, 0.52), while stratified by condom use, the IRR was 0.33(0.17,0.64). The IRR comparing incidence in couples reporting "consistent condom use" versus those reporting otherwise was 0.02(95%CI:0.01,0.04), after stratified by ART use level, the IRR was 0.01(95%CI: 0.00, 0.06). CONCLUSIONS: ART use by index partners could reduce HIV transmission in serodiscordant couples, and the effectiveness of this prevention strategy could be further increased with consistent condom use.

Introduction: Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner's HIV testing. Methods: Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2-3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression. A qualitative study including 37 individual interviews with men, women, and nurses and 11 focus group discussions (n=94) with men, women and grandmothers explored motivators and barriers to uptake of male HIV testing. Results: HIV incidence rate was estimated at 4.28/100 women-years (95% CI: 2.33-7.16). Significant risk factors for HIV acquisition were early sexual debut (RR 3.79, 95% CI: 1.04-13.78, p=0.04) and living in Maputo Province (RR 4.35, 95% CI: 0.97-19.45, p=0.05). Nineteen percent of women reported that their partner had tested for HIV (93% knew the result with 8/213 indicating an HIV positive partner), 56% said their partner had not tested and 19% did not know their partner test status. Of the 14 seroconversions, only one reported being in a serodiscordant relationship. Fear of discrimination or stigma was reported as a key barrier to male HIV testing, while knowing the importance of getting tested and receiving care was the main motivator. Conclusions: HIV incidence during pregnancy is high in Southern Mozambique, but knowledge of partners' HIV status remains low. Knowledge of both partners' HIV status is critical for maximal effectiveness of prevention and treatment services to reach elimination of pediatric HIV/AIDS.

BackgroundCountries are currently progressing towards the elimination of new paediatric HIV infections by 2015. WHO published new consolidated guidelines in June 2013, which now recommend either 'Antiretroviral drugs (ARVs) for women living with HIV during pregnancy and breastfeeding (Option B)' or 'Lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women living with HIV (Option B+)', while de facto phasing out Option A. This study examined health outcomes and cost impact of the shift to WHO 2013 recommendations in Zambia.MethodsA decision analytic model was developed based on the national health system perspective. Estimated risk and number of cases of HIV transmission to infants and to serodiscordant partners, and proportions of HIV-infected pregnant women with CD4 count of ≤350 cells/mm3 to initiate ART were compared between 2010 Option A and the 2013 recommendations. Total costs of prevention of mother-to-child transmission of HIV (PMTCT) services per annual cohort of pregnant women, incremental cost-effectiveness ratio (ICER) per infection averted and quality-adjusted life-year (QALY) gained were examined.ResultsOur analysis suggested that the shift from 2010 Option A to the 2013 guidelines would result in a 33% reduction of the risk of HIV transmission among exposed infants. The risk of transmission to serodiscordant partners for a period of 24 months would be reduced by 72% with 'ARVs during pregnancy and breastfeeding' and further reduced by 15% with 'Lifelong ART'. The probability of HIV-infected pregnant women to initiate ART would increase by 80%. It was also suggested that while the shift would generate higher PMTCT costs, it would be cost-saving in the long term as it spares future treatment costs by preventing infections in infants and partners.ConclusionThe shift to the WHO 2013 guidelines in Zambia would positively impact health of family and save future costs related to care and treatment.

Understanding the relative contribution to HIV transmission from different social groups is important for public-health policy. Information about the importance of stable serodiscordant couples (when one partner is infected but not the other) relative to contacts outside of stable partnerships in spreading disease can aid in designing and targeting interventions. However, the overall importance of within-couple transmission, and the determinants and correlates of this importance, are not well understood. Here, we explore how mechanistic factors - like partnership dynamics and rates of extra-couple transmission - affect various routes of transmission, using a compartmental model with parameters based on estimates from Sub-Saharan Africa. Under our assumptions, when sampling model parameters within a realistic range, we find that infection of uncoupled individuals is usually the predominant route (median 0.62, 2.5%-97.5% quantiles: 0.26-0.88), while transmission within discordant couples is usually important, but rarely represents the majority of transmissions (median 0.33, 2.5%-97.5% quantiles: 0.10-0.67). We find a strong correlation between long-term HIV prevalence and the contact rate of uncoupled individuals, implying that this rate may be a key driver of HIV prevalence. For a given level of prevalence, we find a negative correlation between the proportion of discordant couples and the within-couple transmission rate, indicating that low discordance in a population may reflect a relatively high rate of within-couple transmission. Transmission within or outside couples and among uncoupled individuals are all likely to be important in sustaining heterosexual HIV transmission in Sub-Saharan Africa. Hence, intervention policies should be broadly targeted when practical.

BACKGROUND: Early initiation of antiretroviral therapy reduces risk of transmission to the uninfected partner in HIV discordant couples, but there are relatively little observational data on HIV transmission within couples from non-trial settings. The aims of this paper are to estimate HIV incidence among HIV discordant couples using longstanding observational data from a rural Ugandan population and to identify factors associated with HIV transmission within couples, including the role of HSV-2 infection. METHODS: Using existing data collected at population-wide annual serological and behavioural surveys in a rural district in southwest Uganda between 1989 and 2007, HIV discordant partners were identified. Stored serum samples were tested for HSV-2 serostatus using the Kalon ELISA test. HIV seroconversion rates and factors association with HIV seroconversion were analysed using Poisson regression. RESULTS: HIV status of both partners was known in 2465 couples and of these 259 (10.5%) were HIV serodiscordant. At enrollment, HSV-2 prevalence was 87.3% in HIV positive partners and 71.5% in HIV negative partners. Of the 259 discordant couples, 62 converted to HIV (seroconversion rate 7.11/100 PYAR, 95%CI; 5.54, 9.11) with the rate decreasing from 10.89 in 1990-1994 to 4.32 in 2005-2007. Factors independently associated with HIV seroconversion were female sex, non-Muslim religion, greater age difference (man older than woman by more than 15 years), higher viral load in the positive partner and earlier calendar period. HSV-2 was not independently associated with HIV acquisition (HR 1.62, 95%CI; 0.57, 4.55) or transmission (HR 0.61, 95%CI; 0.24, 1.57). No transmissions occurred in the 29 couples where the index partner was on ART during follow up (872 person-years on ART). DISCUSSION: HIV negative partners in serodiscordant couples have a high incidence of HIV if the index partner is not on antiretroviral therapy and should be provided with interventions such as couple counselling, condoms and antiretroviral treatment.

Background The risk of sexual HIV transmission in serodiscordant couples when the HIV-positive partner has full virologic suppression on combination antiretroviral therapy (cART) is debated. This study aims to systematically review observational studies and randomized controlled trials (RCTs), evaluating rates of sexual HIV transmission between heterosexual serodiscordant couples when the HIV-positive partner has full suppression on cART. Methods and Findings We searched major bibliographic databases to November 2012 for relevant observational studies and RCTs without language restrictions. Conference proceedings, key journals and bibliographies were also searched. Studies reporting HIV transmission rates, cART histories and viral loads of the HIV-positive partners were included. Two reviewers extracted methodologic characteristics and outcomes. Of 20,252 citations, 3 studies met all eligibility criteria with confirmed full virologic suppression in the HIV-positive partner. We included 3 additional studies (2 cohort studies, 1 RCT) that did not confirm viral suppression in the HIV-positive partner at transmission in a secondary meta-analysis. Methodologic quality was reasonable. The rate of transmission in the 3 studies confirming virologic suppression was 0 per 100 person-years (95% CI = 0–0.05), with low heterogeneity (I2 = 0%). When we included the 3 studies that did not confirm virologic suppression, the rate of transmission was 0.14 per 100 person-years (95%CI = 0.04–0.31) (I2 = 0%). In a sensitivity analysis including all 6 studies, the rate of transmission was 0 per 100 person-years (95%CI = 0–0.01) after omitting all transmissions with known detectable or unconfirmed viral loads, as full suppression in these cases was unlikely. Limitations included lack of data on same-sex couples, type of sexual intercourse (vaginal vs. anal), direction of HIV transmission, exact viral load at the time of transmission, sexually transmitted infections (STI) rates, and extent of condom use. Conclusions Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health. More research is needed to explore HIV transmission risk between same-sex couples.

Background Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration Clinicaltrials.gov number NCT00931346

Objective We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive) male couples' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple. Design Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it. Methods We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes. Results Among 328 men (164 couples), 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse. Conclusions Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact.

HIV 'treatment as prevention' (TasP) is highly effective in reducing HIV transmission in serodiscordant couples. There has been little examination of gay and bisexual men's attitudes towards TasP, particularly regarding men's willingness to act on beliefs about TasP. We conducted an online cross-sectional survey of Australian men in late 2012 to investigate knowledge and beliefs about new developments in HIV prevention. Amongst 839 men (mean age 39.5 years), men tended to disagree that TasP was sufficiently effective to justify reduced condom use, although HIV-positive men had more favourable attitudes. Only a minority of men were aware of any evidence for TasP; and one-quarter incorrectly believed that evidence for the effectiveness of TasP already existed for the homosexual population. One-fifth (20.5%) of men reported that they would be willing to have condomless anal intercourse with an opposite-status sexual partner when the HIV-positive partner was taking HIV treatments. Factors independently associated with such willingness were: HIV-positive serostatus, reporting any serodiscordant or serononconcordant condomless anal intercourse with a regular male partner in the previous six months, reporting any condomless anal intercourse with a casual male partner in the previous six months, and having greater beliefs in the effectiveness of TasP. This indicated that the men most willing to rely on TasP to prevent transmission were already engaging in higher risk practices. Biomedical HIV prevention represents a rapidly changing environment with new research as well as community and policy responses emerging at a fast pace. For men with serodiscordant sexual partners to successfully apply TasP to reducing transmission risk, more support and education is needed to enable better utilisation of TasP in specific relational and sexual contexts.

Background HIV exposed seronegative (HESN) women represent the population most in need of a prophylactic antiviral strategy. Mucosal cationic polypeptides can potentially be regulated for this purpose and we here aimed to determine their endogenous expression and HIV neutralizing activity in genital secretions of women at risk of HIV infection. Methodology/Principal Findings Cervicovaginal secretions (CVS) of Kenyan women in HIV-serodiscordant relationships (HESN, n = 164; HIV seropositive, n = 60) and low-risk controls (n = 72) were assessed for the cationic polypeptides HNP1–3, LL-37 and SLPI by ELISA and for HIV neutralizing activity by a PBMC-based assay using an HIV primary isolate. Median levels of HNP1–3 and LL-37 in CVS were similar across study groups. Neither HSV-2 serostatus, nor presence of bacterial vaginosis, correlated with levels of HNP1–3 or LL-37 in the HESN women. However, an association with their partner's viral load was observed. High viral load (>10,000 HIV RNA copies/ml plasma) correlated with higher levels of HNP1–3 and LL-37 (p = 0.04 and 0.03, respectively). SLPI was most abundant in the low-risk group and did not correlate with male partner's viral load in the HESN women. HIV neutralizing activity was found in CVS of all study groups. In experimental studies, selective depletion of cationic polypeptides from CVS rendered the remaining CVS fraction non-neutralizing, whereas the cationic polypeptide fraction retained the activity. Furthermore, recombinant HNP1–3 and LL-37 could induce neutralizing activity when added to CVS lacking intrinsic activity. Conclusions/Significance These findings show that CVS from HESN, low-risk, and HIV seropositive women contain HIV neutralizing activity. Although several innate immune proteins, including HNP1–3 and LL-37, contribute to this activity these molecules can also have inflammatory properties. This balance is influenced by hormonal and environmental factors and in the present HIV serodiscordant couple cohort study we show that a partner's viral load is associated with levels of such molecules.

Introduction: The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future. Methods: We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods. Results: 318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of #18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men’s risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p#0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p=0.004) and those who were HIV seropositive (APR 1.09, p=0.03) were also more likely to be interested in child circumcision for HIV prevention. Conclusions: A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention.

Background: Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners. Methodology/Principal Findings: We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners’ sequences and a Bayesian posterior probability of $50%. Adjudicators classified each seroconversion, finding 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%). Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters. Conclusions/Significance: In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than onefourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage determination process.

Background Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use. Methods We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations. Results After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations. Conclusion This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition.

Background Acquisition of human immunodeficiency virus type 1 (HIV-1) infection is mediated by a combination of characteristics of the infectious and the susceptible member of a transmission pair, including human behavioral and genetic factors, as well as viral fitness and tropism. Here we report on the impact of established and potential new HLA class I determinants of heterosexual HIV-1 acquisition in the HIV-1-exposed seronegative (HESN) partners of serodiscordant Zambian couples. Methodology/Principal Findings We assessed the relationships of behavioral and clinically documented risk factors, index partner viral load, and host genetic markers to HIV-1 transmission among 568 cohabiting couples followed for at least nine months. We genotyped subjects for three classical HLA class I genes known to influence immune control of HIV-1 infection. From 1995 to December 2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were significantly and independently associated with faster HIV-1 acquisition (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively) after controlling for other previously established contributing factors in the index partner (viral load and specific class I alleles), in the HESN partner (age, gender), or in the couple (behavioral and clinical risk score). Few if any previously implicated class I markers were associated here with the rate of acquiring infection. Conclusions/Significance A few HLA class I markers showed modest effects on acquisition of HIV-1 subtype C infection in HESN partners of discordant Zambian couples. However, the striking disparity between those few markers and the more numerous, different markers found to determine HIV-1 disease course makes it highly unlikely that, whatever the influence of class I variation on the rate of infection, the mechanism mediating that phenomenon is identical to that involved in disease control.

Objective To describe the quality of life and related factors in HIV-positive spouses undergoing ART from discordant couples. Methods A cross-sectional study was conducted among 1,009 HIV-positive spouses from serodiscordant couples in Zhumadian, Henan Province, between October 1, 2008 and March 31, 2009. HIV-positive spouses were interviewed by local health professionals. Quality of life was evaluated by WHOQOL (Chinese Version). A multiple linear regression model was used to analyze the related factors. Results The majority of subjects were female (56.39%), had received a high school education (44%), were of Han ethnicity (98.41%), and were farmers (90.09%); the median time period of receiving ART was 3.92 years. The physical, psychological, social, and environmental QOL scores of the subjects were 12.91±1.95, 12.35±1.80, 13.96±2.43, and 12.45±1.91 respectively. The multiple linear regression model identified the physical domain related factors to be CD4 count, educational level, and occupation; psychological domain related factors include age, educational level, and reported STD symptom; social domain related factors included education level; and environmental domain related factors included education level, reported STD symptoms, and occupation. Conclusion Being younger, a farmer, having a lower level of education, a reported STD symptom, or lower CD4 count, could decrease one's quality of life, suggesting that the use of blanket ART programs alone may not necessarily improve quality of life. Subjects received lower scores in the psychological domain, suggesting that psychological intervention may also need to be strengthened.

BackgroundThe Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.MethodsHIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.ResultsOf the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to

© 2015 Karita et al.Background: 2013 WHO guidelines recommend starting ART at CD4+ T-cell counts ≤500 cells/μL. We present the T-cell counts from adult Africans with HIV shortly following transmission to their sexual partners. Methods: HIV-discordant couples in Zambia, Uganda and Rwanda were followed prospectively and received couples counseling and condoms. HIV uninfected partners were tested for HIV at least quarterly and HIV-infected partners received HIV care and referral for ART per national guidelines. Upon diagnosis of incident HIV infection in the previously HIV-uninfected partner, a blood sample was collected from both partners to measure CD4+ T-cells and perform viral linkage. The estimated date of infection (EDI) of the incident case was calculated based on testing history. EDI was unknown for suspected transmitting partners. Results: From 2006-2011, 4,705 HIV-discordant couples were enrolled in this cohort, and 443 cases of incident HIV infection were documented. Virus linkage analysis was performed in 374 transmission pairs, and 273 (73%) transmissions were linked genetically. CD4 counts in the transmitting partner were measured a median of 56 days after EDI (mean:90.5, min:10, max:396). The median CD4 count was 339 cells/μl (mean:386.4, min:15, max:1,434), and the proportion of partners with a CD4+ T-cell count above 500/μl was 25% (95% CI:21, 31). Conclusions: In our cohort of discordant couples, 73% of HIV transmissions occurred within the relationship, and the transmitter CD4+ T cell count shortly after the transmission event was frequently higher than the WHO 2013 ART-initiation guidelines. Copyright

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

Objectives We aimed to investigate the awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among HIV-negative partners in HIV-serodiscordant heterosexual couples in Xinjiang, China and determine factors that predict willingness to use oral PrEP. Methods Between November 2009 and December 2010, a cross-sectional survey was carried out among 351 HIV-negative partners in HIV-serodiscordant heterosexual couples from three cities in Xinjiang, China. Participants completed a self-administered questionnaire to assess their awareness of and willingness to use oral PrEP. Additionally, blood samples were collected to test for HIV infection. Univariate and multivariate logistic regression analyses were performed to identify predictors of willingness to use oral PrEP. Results Only 10 participants (2.8%) reported having heard of PrEP, and only two reported ever using PrEP. However, 297 (84.6%) reported that they were willing to use oral PrEP if it was proven to be both safe and effective. Results of multivariate analysis revealed the following independent predictors of willingness to use oral PrEP: monthly household income (adjusted odds ratio = 2.78

Background: Current WHO guidelines recommend antiretroviral therapy (ART) initiation at CD4 counts #350 cells/mL. Increasing this threshold has been proposed, with a primary goal of reducing HIV-1 infectiousness. Because the quantity of HIV-1 in plasma is the primary predictor of HIV-1 transmission, consideration of plasma viral load in ART initiation guidelines is warranted. Methods: Using per-sex-act infectivity estimates and cross-sectional sexual behavior data from 2,484 HIV-1 infected persons with CD4 counts .350 enrolled in a study of African heterosexual HIV-1 serodiscordant couples, we calculated the number of transmissions expected and the number potentially averted under selected scenarios for ART initiation: i) CD4 count ,500 cells/mL, ii) viral load $10,000 or $50,000 copies/mL and iii) universal treatment. For each scenario, we estimated the proportion of expected infections that could be averted, the proportion of infected persons initiating treatment, and the ratio of these proportions. Results: Initiating treatment at viral load $50,000 copies/mL would require treating 19.8% of infected persons with CD4 counts .350 while averting 40.5% of expected transmissions (ratio 2.0); treating at viral load $10,0000 copies/mL had a ratio of 1.5. In contrast, initiation at CD4 count ,500 would require treating 41.8%, while averting 48.4% (ratio 1.1). Conclusion: Inclusion of viral load in ART initiation guidelines could permit targeting ART resources to HIV-1 infected persons who have a higher risk of transmitting HIV-1. Further work is needed to estimate costs and feasibility.

Background: The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions. Methodology/Principal Findings: We use prospective data collected from 2004 to 2008 in East and Southern African HIV-1 serodiscordant couples to model the relationship of plasma HIV-1 RNA levels and heterosexual transmission risk with confirmation of HIV-1 transmission events by HIV-1 sequencing. The model is based on follow-up of 3381 HIV-1 serodiscordant couples over 5017 person-years encompassing 108 genetically-linked HIV-1 transmission events. HIV-1 transmission risk was 2.27 per 100 person-years with a log-linear relationship to log10 plasma HIV-1 RNA. The model predicts that a decrease in average plasma HIV-1 RNA of 0.74 log10 copies/mL (95% CI 0.60 to 0.97) reduces heterosexual transmission risk by 50%, regardless of the average starting plasma HIV-1 level in the population and independent of other HIV-1-related population characteristics. In a simulated population with a similar plasma HIV-1 RNA distribution the model estimates that 90% of overall HI V-1 infections averted by a0 .74 copies/mL reduction in plasma HIV-1 RNA could be achieved by targeting this reduction to the 58% of the cohort with plasma HIV-1 levels $4 log10 copies/mL. Conclusions/Significance: This log-linear model of plasma HIV-1 levels and risk of sexual HIV-1 transmission may help estimate the impact on HIV-1 transmission and infections averted from candidate interventions that reduce plasma HIV-1 RNA levels.