HIV Acquisition In Women Research Articles

Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study

Disruptions of vaginal microbiota might increase women's susceptibility to HIV infection. Advances in molecular microbiology have enabled detailed examination of associations between vaginal bacteria and HIV acquisition. Therefore, this study aimed to evaluate the association between the concentrations of specific vaginal bacteria and increased risk of HIV acquisition in African women. We did a nested case-control study of participants from eastern and southern Africa. Data from five cohorts of African women (female sex workers, pregnant and post-partum women, and women in serodiscordant relationships) were used to form a nested case-control analysis between women who acquired HIV infection versus those who remained seronegative. Deep sequence analysis of broad-range 16S rRNA gene PCR products was applied to a subset of 55 cases and 55 controls. From these data, 20 taxa were selected for bacterium-specific real-time PCR assays, which were examined in the full cohort as a four-category exposure (undetectable, first tertile, second tertile, and third tertile of concentrations). Conditional logistic regression was used to generate odds ratios (ORs) and 95% CIs. Regression models were stratified by cohort, and adjusted ORs (aORs) were generated from a multivariable model controlling for confounding variables. The Shannon Diversity Index was used to measure bacterial diversity. The primary analyses were the associations between bacterial concentrations and risk of HIV acquisition. Between November, 2004, and August, 2014, we identified 87 women who acquired HIV infection (cases) and 262 controls who did not acquire HIV infection. Vaginal bacterial community diversity was higher in women who acquired HIV infection (median 1·3, IQR 0·4-2·3) than in seronegative controls (0·7, 0·1-1·5; p=0·03). Seven of the 20 taxa showed significant concentration-dependent associations with increased odds of HIV acquisition: Parvimonas species type 1 (first tertile aOR 1·67, 95% CI 0·61-4·57; second tertile 3·01, 1·13-7·99; third tertile 4·64, 1·73-12·46; p=0·005) and type 2 (first tertile 3·52, 1·63-7·61; second tertile 0·85, 0·36-2·02; third tertile 2·18, 1·01-4·72; p=0·004), Gemella asaccharolytica (first tertile 2·09, 1·01-4·36; second tertile 2·02, 0·98-4·17; third tertile 3·03, 1·46-6·30; p=0·010), Mycoplasma hominis (first tertile 1·46, 0·69-3·11; second tertile 1·40, 0·66-2·98; third tertile 2·76, 1·36-5·63; p=0·048), Leptotrichia/Sneathia (first tertile 2·04, 1·02-4·10; second tertile 1·45, 0·70-3·00; third tertile 2·59, 1·26-5·34; p=0·046), Eggerthella species type 1 (first tertile 1·79, 0·88-3·64; second tertile 2·62, 1·31-5·22; third tertile 1·53, 0·72-3·28; p=0·041), and vaginal Megasphaera species (first tertile 3·15, 1·45-6·81; second tertile 1·43, 0·65-3·14; third tertile 1·32, 0·57-3·05; p=0·038). Differences in the vaginal microbial diversity and concentrations of key bacteria were associated with greater risk of HIV acquisition in women. Defining vaginal bacterial taxa associated with HIV risk could point to mechanisms that influence HIV susceptibility and provide important targets for future prevention research. National Institute of Child Health and Human Development.

The microbiome and HIV prevention strategies in women.

HIV prevention approaches that women can use and control are a priority. Results from topical and oral preexposure prophylaxis (PrEP) HIV prevention trials have produced inconsistent results in women. One of the main behavioural factors impacting effectiveness of PrEP has been suboptimal adherence. In this review, we examine biological factors that modulate topical PrEP efficacy, with particular focus on the vaginal microbiome. Genital inflammation is an independent risk factor for HIV acquisition in women. Using 16S rRNA sequencing of the vaginal microbiota, anaerobic bacteria linked with bacterial vaginosis have been shown to be associated with both genital inflammation and HIV risk. Using proteomics, it was recently discovered that a dysbiotic vaginal microbiome, comprising less than 50% Lactobacillus spp., directly influenced topical PrEP efficacy. Gardnerella vaginalis, the dominant vaginal species in dysbiotic women, was able to directly degrade tenofovir, but not dapivirine, an antiretroviral also being developed for topical PrEP. The link between bacterial vaginosis-associated organisms with HIV risk and altered tenofovir gel effectiveness underscores the importance of good vaginal health and good adherence for women to benefit maximally from topical PrEP. Altering the vaginal microbiome is one of the new directions being pursued for HIV prevention.

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

Objective:To quantify the contribution of specific sexual partner age groups to the risk of HIV acquisition in men and women in a hyperendemic region of South Africa.Design:We conducted a population-based cohort study among women (15–49 years of age) and men (15–55 years of age) between 2004 and 2015 in KwaZulu-Natal, South Africa.Methods:Generalized additive models were used to estimate smoothed HIV incidence rates across partnership age pairings in men and women. Cox proportional hazards regression was used to estimate the relative risk of HIV acquisition by partner age group.Results:A total of 882 HIV seroconversions were observed in 15 935 person-years for women, incidence rate = 5.5 per 100 person-years [95% confidence interval (CI), 5.2–5.9] and 270 HIV seroconversions were observed in 9372 person-years for men, incidence rate = 2.9 per 100 person-years (95% CI, 2.6–3.2). HIV incidence was highest among 15–24-year-old women reporting partnerships with 30–34-year-old men, incidence rate = 9.7 per 100 person-years (95% CI, 7.2–13.1). Risk of HIV acquisition in women was associated with male partners aged 25–29 years (adjusted hazard ratio; aHR = 1.44, 95% CI, 1.02–2.04) and 30–34 years (aHR = 1.50, 95% CI, 1.08–2.09) relative to male partners aged 35 and above. Risk of HIV acquisition in men was associated with 25–29-year-old (aHR = 1.72, 95% CI, 1.02–2.90) and 30–34-year-old women (aHR = 2.12, 95% CI, 1.03–4.39) compared to partnerships with women aged 15–19 years.Conclusion:Age of sexual partner is a major risk factor for HIV acquisition in both men and women, independent of one's own age. Partner age pairings play a critical role in driving the cycle of HIV transmission.

Challenges in conducting research on sexual violence and HIV and approaches to overcome them.

Studies have implicated sexual violence as a strong correlate of HIV acquisition in women. Characterizing how such violence affects the female immune system may provide insight into the biological mechanisms of HIV transmission and ultimately improve global HIV prevention strategies. Little research has been carried out in this domain, and the obstacles to investigation can be daunting. Here, we describe methodological challenges encountered and solutions explored while implementing a study of dysregulation of immune biomarkers potentially indicative of increased HIV susceptibility in women following sexual assault. Challenges included accessing sexual assault survivors and defining sexual assault, promoting study participant well-being during research engagement, reducing selection and information bias, collecting and processing biological samples, and adjusting for confounders such as reproductive tract infections and emotional and physical abuse. We found that many survivors of sexual assault welcomed the attention from study staff and felt empowered by the opportunity to help other women at risk for violence. Well-trained research staff and well-articulated community and medical partnerships were key methods to overcoming challenges while promoting the safety and welfare of vulnerable study participants.

Genital-Systemic Chemokine Gradients and the Risk of HIV Acquisition in Women.

Mucosal and systemic immune mediators have been independently associated with HIV acquisition risk, but the relationship between compartments remains unclear. To address this, the concentrations of 12 cytokines were compared in matched plasma and cervicovaginal lavages (CVLs) from 57 HIV-positive women before their acquisition of HIV (cases) and 50 women who remained uninfected (controls) during the CAPRISA 004 trial. Although genital IP-10 concentrations were significantly higher in cases, plasma IP-10 concentrations were inversely associated with HIV risk. Comparing differences in mucosal and systemic cytokine concentrations between cases and controls, mucosa-biased gradients indicating higher cervicovaginal lavage relative to plasma concentrations were observed for all 5 chemokines in the panel. Four were significantly associated with HIV acquisition, including IP-10 (odds ratio [OR] 1.73, 95% confidence interval [CI]: 1.27 to 2.36), macrophage inflammatory protein-1β (OR 1.72, 95% CI: 1.23 to 2.40), interleukin (IL)-8 (OR 1.50, 95% CI: 1.09 to 2.05), and monocyte chemotactic protein-1 (OR 1.36, 95% CI: 1.01 to 1.83). None of the other 7 cytokines tested predicted HIV risk. Decision tree analyses confirmed this association, with gradients of IP-10, IL-8, and granulocyte-macrophage colony-stimulating factor concentrations correctly classifying 77% of HIV outcomes. Our findings suggest that mucosa-biased gradients of IP-10, macrophage inflammatory protein-1β, IL-8, and monocyte chemotactic protein-1 are associated with an increased risk of HIV infection.

Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women

Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4+ Tcells compared to those with Lactobacillus crispatus-dominant communities. We identified specific bacterial taxa linked with reduced (L.crispatus) or elevated (Prevotella, Sneathia, and other anaerobes) inflammation and HIV infection and found that high-risk bacteria increased numbers of activated genital CD4+ Tcells in a murine model. Our results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings might be leveraged to reduce HIV acquisition in women living in sub-Saharan Africa.

An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women

Objective and design:Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data.Methods:We searched for articles published between 15 January 2014 and 15 January 2016 and hand-searched reference lists. We identified longitudinal studies comparing users of a specific hormonal contraceptive method against either nonusers of hormonal contraception or users of another specific hormonal contraceptive method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus non-use of hormonal contraception.Results:We identified 10 new reports of which five were considered ‘unlikely to inform the primary question’. We focus on the other five reports, along with nine from the previous review, which were considered ‘informative but with important limitations’. The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate, and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher quality studies on DMPA (or nondisaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher quality studies of hazard ratio 1.4.Conclusion:Although confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely hazard ratio 1.5 or less. Data for other hormonal contraceptive methods, including norethisterone enanthate, are largely reassuring.

Preferred Physical Characteristics of Vaginal Film Microbicides for HIV Prevention in Pittsburgh Women.

Unprotected heterosexual intercourse is the leading cause of HIV acquisition in women. Due to the complex nature of correct and consistent condom use by both men and women, developing alternative female-controlled HIV prevention options is a global health priority. Vaginal films containing antiretroviral drugs are a potential delivery system for the prevention of HIV acquisition through sexual contact. In this study, we explored women's preferences regarding physical characteristics of microbicide vaginal films through questionnaires and focus groups. Eighty-four sexually active, ethnically diverse women 18-30years of age from Pittsburgh, Pennsylvania, participated in the study. Women visually and manually examined a variety of vaginal films, as well as three other vaginal products undergoing evaluation for HIV prevention: tablet, ring, and gel. Means and standard deviations or frequencies and 95% confidence intervals were calculated for questionnaire data. Focus groups were audio-recorded, transcribed verbatim, and coded for content analysis. Women most frequently preferred vaginal films to be smooth and thin (63%), translucent (48%), and 2″×2″ square size (36%). Driving these preferences were five major themes: ease and accuracy of use, desire for efficacy, discretion, intravaginal comfort and minimal impact, and minimizing disruption of sexual mood/activities. Women's preferences for various microbicide vaginal film physical attributes represented a balance of multiple values. In general, women desired a comfortable, efficacious, easy to use, and minimally intrusive product.

Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.

Correction to: Mucosal Immunology (2016); advance online publication, 27 January 2016; doi: 10.1038/mi.2015.145 The version of this article published online contained several incorrect elements: some of the authors' names and some of the affiliations; Figures 1 and 3; Tables 2 and 3; some references; Supplementary Figures 2–6. Correction to: Mucosal Immunology (2016); advance online publication, 27 January 2016; doi: 10.1038/mi.2015.145 The version of this article published online contained several incorrect elements: some of the authors' names and some of the affiliations; Figures 1 and 3; Tables 2 and 3; some references; Supplementary Figures 2–6. Correction to:Mucosal Immunology (2016); advance online publication, 27 January 2016; doi: https://doi.org/10.1038/mi.2015.145 The version of this article published online contained several incorrect elements: some of the authors' names and some of the affiliations; Figures 1 and 3; Tables 2 and 3; some references; Supplementary Figures 2–6. The Supplementary Figures appear online via the online version of this erratum. The article published in this issue incorporates all the corrected elements listed above. The publisher regrets the errors. Distinct genital tract HIV-specific antibody profiles associated with tenofovir gelMucosal ImmunologyVol. 9Issue 3PreviewThe impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisition in women assigned to tenofovir gel (n=24) and placebo gel (n=24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Full-Text PDF Open Archive

Tenofovir-based oral preexposure prophylaxis prevents HIV infection among women.

Despite tremendous promise as a female-controlled HIV prevention strategy, implementation of preexposure prophylaxis (PrEP) among women has been limited, in part because of disparate efficacy results from randomized trials in this population. This review synthesizes existing evidence regarding PrEP efficacy for preventing HIV infection in women and considerations for delivering PrEP to women. In three efficacy trials, conducted among men and women, tenofovir-based oral PrEP reduced HIV acquisition in subgroups of women by 49-79% in intent-to-treat analyses, and by >85% when accounting for PrEP adherence. Two trials did not demonstrate an HIV prevention benefit from PrEP in women, but substantial evidence indicates those results were compromised by very low adherence to the study medication. Qualitative research has identified risk perception, stigma, and aspects of clinical trial participation as influencing adherence to study medication. Pharmacokinetic studies provide supporting evidence that PrEP offers HIV protection in women who are adherent to the medication. Tenofovir-based daily oral PrEP prevents HIV acquisition in women. Offering PrEP as an HIV prevention option for women at high risk of HIV acquisition is a public health imperative and opportunities to evaluate implementation strategies for PrEP for women are needed.

An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women

An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women

The role of progestins in HIV acquisition in young women

In The Lancet Infectious Diseases Elizabeth Byrne and colleagues report the biological mechanism by which injectable progestin-only contraceptives such as depot medroxy progesterone acetate (DMPA) and norethindrone enanthate (NET-EN) or endogenous progesterone might act to increase the risk of HIV acquisition in women. They report that HIV-negative injectable progestin-only contraceptive users had a 3·92 times higher frequency of cervical HIV target cells than women using no long-term contraceptive (p=0·0241) and women using no long-term contraceptive in the luteal phase of the menstrual cycle (a naturally high-progestin state) also had a 3·25 times higher frequency of cervical target cells than those in the lower-progestin follicular phase (p=0·0488). The study by Byrne and colleagues has several limitations. First the number of seroconversions was small and the analyses were limited to a subset within the cohort. Although screening for HIV was twice a week genital and other samples were only collected every 3 months which means women receiving DMPA would be sampled at the same time as their injection cycle. Hence the findings reported here need to be assessed in a prospective cohort with more frequent purposive sampling designed to address the biological pathway more specifically. Byrne and colleagues report ongoing high incidence of HIV in this population of young women emphasising the fact that HIV is far from eliminated in this setting. Therefore clearly in southern Africa an urgent need exists to scale up integrated family planning and HIV prevention service provision for women. (Excerpts) Copyright © 2016 Elsevier Ltd.

Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study

The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies, but the biological mechanisms of this risk remain poorly understood. We aimed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract. In this prospective cohort, we enrolled HIV-negative South African women aged 18-23 years who were not pregnant and were living in Umlazi, South Africa from the Females Rising through Education, Support, and Health (FRESH) study. We tested for HIV-1 twice per week to monitor incident infection. Every 3 months, we collected demographic and behavioural data in addition to blood and cervical samples. The study objective was to characterise host immune determinants of HIV acquisition risk, including those associated with injectable progestin-only contraceptive use. Hazard ratios (HRs) were estimated using Cox proportional hazards methods. Between Nov 19, 2012, and May 31, 2015, we characterised 432 HIV-uninfected South African women from the FRESH study. In this cohort, 152 women used injectable progestin-only contraceptives, 43 used other forms of contraception, and 222 women used no method of long-term contraception. Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV (12·06 per 100 person-years, 95% CI 6·41-20·63) than women using no long-term contraception (3·71 per 100 person-years, 1·36-8·07; adjusted hazard ratio [aHR] 2·93, 95% CI 1·09-7·868, p=0·0326). HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells (CCR5+ CD4 T cells) compared with women using no long-term contraceptive (p=0·0241). Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase (p=0·0488), suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives. Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix, the site of initial HIV entry in most women, providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure. The Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases.

Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition.

Greater inhibitory activity against Escherichia coli and levels of human β defensin (HBD)-2 in genital tract secretions predicted HIV acquisition in women in the HPTN 035 trial. We investigated whether higher levels of E. coli inhibitory activity and antimicrobial peptides in cervicovaginal lavage (CVL) samples predicted HIV acquisition in women in the CAPRISA 002 Acute Infection Study. E. coli inhibitory activity and antimicrobial peptides were quantified in CVL from a subset of CAPRISA 002 participants who did not seroconvert (n=39) and from seroconverting women prior to infection (n=17) and during acute infection (n=11). Women who acquired HIV had significantly greater preinfection CVL E. coli inhibitory activity (p=0.01) and HBD-1 levels (p=0.02) compared to women who remained uninfected. Preinfection E. coli inhibitory activity remained significantly associated with seroconversion following adjustment for the presence of bacterial vaginosis (OR 1.45; 95% CI 1.07, 1.97). Partial least squares discriminant analysis confirmed that preinfection CVL E. coli inhibitory activity, together with higher CVL concentrations of HBD-1 and secretory leukocyte protease inhibitor, distinguished seroconverters from nonseroconverters with 67% calibration accuracy. CVL concentrations of human neutrophil peptides (HNP) 1-3 increased significantly with acute infection (p=0.001) and correlated with plasma viral set point (r=0.66, p=0.03). E. coli inhibitory activity in genital tract secretions could provide a biomarker of HIV risk. The correlation between HNP 1-3 and viral set point merits further investigation of the relationship between mucosal inflammation during early HIV infection and disease progression.

Partner Age-Disparity and HIV Incidence Risk for Older Women in Rural South Africa.

While sexual partner age disparity is frequently considered as a potential risk factor for HIV among young women in Africa, no research has addressed this question among older women. Our aim was thus to determine whether sex partner age disparity was associated with subsequent HIV acquisition in women over 30 years of age. To achieve this aim we conducted a quantitative analysis of a population-based, open cohort of women in rural KwaZulu-Natal, South Africa (n = 1,737) using Cox proportional hazards models. As partner age rose, HIV acquisition risk fell significantly: compared to a same-aged partner, a 5-year older partner was associated with a one-third reduction [hazard ratio (HR) 0.63, 95 % CI 0.52-0.76] and a 10-year older partner with a one-half reduction (HR 0.48, 95 % CI 0.35-0.67) in acquisition risk. This result was neither confounded nor effect-modified by women's age or socio-demographic factors. These findings suggest that existing HIV risk-reduction campaigns warning young women about partnering with older men may be inappropriate for older women. HIV prevention strategies interventions specifically tailored to older women are needed.

Depot-medroxyprogesterone acetate does not reduce the prophylactic efficacy of emtricitabine and tenofovir disoproxil fumarate in macaques.

Concerns that the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) may increase the risk of HIV acquisition in women led to questions on whether DMPA could reduce efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model to investigate the impact of prolonged DMPA exposure on PrEP with emtricitabine/tenofovir disoproxil fumarate. Twelve pigtail macaques treated with DMPA were exposed vaginally to simian HIV once a week for up to 5 months and received either placebo (n = 6) or emtricitabine/tenofovir disoproxil fumarate (n = 6). All control macaques were infected, whereas the PrEP-treated animals remained protected (P = 0.0007). This model suggests that women using DMPA will fully benefit from PrEP.

Policy implications for multipurpose prevention technologies service delivery.

Policy implications for multipurpose prevention technologies service delivery.

CCR5 expression is elevated in cervical cancer cells and is up-regulated by seminal plasma.

The interplay between inflammation, cervical cancer and HIV acquisition in women is poorly understood. We have previously shown that seminal plasma (SP) can promote cervical tumour cell growth in vitro and in vivo via the activation of potent inflammatory pathways. In this study, we investigated whether SP could regulate expression of chemokine receptors with known roles in HIV infection, in the cervix and in cervical cancer. The expression of CD4 and CCR5 was investigated by RT-PCR analysis and immunohistochemistry. CD4 and CCR5 expression was elevated in cervical cancer tissue compared with normal cervix. Ex vivo studies conducted on cervical tissues and HeLa cells showed that SP significantly increases the expression of CD4 and CCR5 transcripts. Furthermore, it was found that SP also up-regulates CCR5 protein in HeLa cells. The regulation of CCR5 expression was investigated following treatment of HeLa cells with SP in the presence/absence of chemical inhibitors of intracellular signalling, EP2 and EP4 antagonists, prostaglandin (PG) E2 and a cyclooxygenase (COX)-1 doxycycline-inducible expression system. These experiments demonstrated that the regulation of CCR5 expression by SP occurs via the epidermal growth factor receptor (EGFR)-COX-1-PGE2 pathway. This study provides a link between activation of inflammatory pathways and regulation of HIV receptor expression in cervical cancer cells.

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

Based on ethnographic investigations and mathematical models, older sexual partners are often considered a major risk factor for HIV for young women in sub-Saharan Africa. Numerous public health campaigns have been conducted to discourage young women from relationships with older men. However, longitudinal evidence relating sex partner age disparity to HIV acquisition in women is limited. Using data from a population-based open cohort in rural KwaZulu-Natal, South Africa, we studied 15- to 29-year-old women who were HIV seronegative at first interview between January 2003 and June 2012 (n = 2444). We conducted proportional hazards analysis to establish whether the age disparity of women's most recent sexual partner, updated at each surveillance round, was associated with subsequent HIV acquisition. A total of 458 HIV seroconversions occurred over 5913 person-years of follow-up (incidence rate: 7.75 per 100 person-years). Age disparate relationships were common in this cohort; 37.7% of women reported a partner 5 or more years older than themselves. The age disparity of women's partners was not associated with HIV acquisition when measured either continuously [hazard ratio (HR) for 1-year increase in partner's age: 1.00, 95% confidence interval (CI): 0.97 to 1.03] or categorically (man ≥5 years older: HR, 0.98; 95% CI: 0.81 to 1.20; man ≥10 years older: HR, 0.98; 95% CI: 0.67 to 1.43). These results were robust to adjustment for known sociodemographic and behavioral HIV risk factors and did not vary significantly by women's age, marital status, education attainment, or household wealth. HIV incidence in young women was very high in this rural community in KwaZulu-Natal. Partner age disparity did not predict HIV acquistion. Campaigns to reduce age-disparate sexual relationships may not be a cost-effective use of HIV prevention resources in this setting.

Marriage and the Risk of Incident HIV Infection in Rakai, Uganda

Studies suggest that the prevalence of HIV is higher among long-term marital/consensual relationships than in the unmarried. We assessed the risk of incident HIV infection by marital status in rural Rakai, Uganda. Longitudinal data from the Rakai Community Cohort Study between 1999 and 2011. We estimated HIV incidence per 100 person years (py) in sexually active individuals aged 15-49 years with a total of 44,179.6 py who were never married (women 2929 py and men 4261 py), currently married or in long-term consensual relationships (currently married women 29,823 py and men 21,299 py) and previously married (women 3563 py and men 1475). Poisson multivariable regression was used to estimate the unadjusted and adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of HIV acquisition. The HIV incidence among currently married persons was 0.93/100 py, which was lower than that for the never-married (1.51/100 py) and previously married (2.85/100 py) persons. The risk of HIV acquisition was significantly lower in the currently married compared with that in the never married among women (Adj IRR = 0.26, 95% CI: 0.16 to 0.42), but not among men (Adj IRR = 0.69, 95% CI: 0.31 to 1.52). HIV incidence was lower among first marriages (0.73/100 py) compared with that among second- or higher-order marriages (1.38/100 py). Multiple sex partners significantly increased the risk of HIV acquisition in both women (Adj IRR = 2.53, 95% CI: 1.6 to 3.97) and men (Adj IRR = 1.77, 95% CI: 1.20 to 2.60). Current marriage especially first-order marriage was associated with a reduced risk of HIV acquisition in women, but not in men, and multiple sex partnerships increased HIV risk for both sexes.