BACKGROUNDTo assess the impact of combination HIV prevention (CHP) on HIV incidence, we analyzed the association between HIV incidence and scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral load suppression and sexual behaviors were also examined.METHODSBetween 1999 and 2016, data were collected through 12 surveys from 30 communities in the Rakai Community Cohort Study, an open population-based cohort of persons aged 15-49 years. We assessed HIV incidence trends based on observed seroconversion data, self-reported ART and male circumcision coverage, viral load suppression, and sexual behaviors.RESULTSIn total, 33,937 study participants contributed 103,011 person-visits (HIV prevalence ~13%). Follow-up of 17,870 HIV-negative persons contributed 94,427 person-years with 931 seroconversions. ART was introduced in 2004; by 2016 coverage was 69% (72% in women vs. 61% in men, p<0.001). HIV viral load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (p<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (p<0.001). Persons 15-19 years reporting n 71 ever having sex increased from 30% to 55% (p<0.0001). HIV incidence declined by 42% in 2016 relative to the pre-CHP period prior to 2010 (1.17/100 py to 0.66/100 py; adjIRR:0.58: 95%CI: 0.45-0.76); declines were greater in men (adjIRR=0.46; 95%CI: 0.29-0.73) than women (adjIRR=0.68, 95%CI: 0.50-0.94).CONCLUSIONSIn this longitudinal study, HIV incidence significantly declined with CHP scale-up, providing empiric evidence that HIV control interventions can have substantial population-level impact. However, additional efforts are needed to overcome gender disparities and achieve HIV elimination.

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition.

Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and poor gynecologic and obstetric outcomes. Male circumcision reduces BV-associated bacteria on the penis and decreases BV in female partners, but the link between penile microbiota and female partner BV is not well understood. We tested the hypothesis that having a female partner with BV increases BV-associated bacteria in uncircumcised men. We characterized penile microbiota composition and density (i.e., the quantity of bacteria per swab) by broad-coverage 16S rRNA gene-based sequencing and quantitative PCR (qPCR) in 165 uncircumcised men from Rakai, Uganda. Associations between penile community state types (CSTs) and female partner’s Nugent score were assessed. We found seven distinct penile CSTs of increasing density (CST1 to 7). CST1 to 3 and CST4 to 7 were the two major CST groups. CST4 to 7 had higher prevalence and abundance of BV-associated bacteria, such as Mobiluncus and Dialister, than CST1 to 3. Men with CST4 to 7 were significantly more likely to have a female partner with a high Nugent score (P = 0.03). Men with two or more extramarital partners were significantly more likely to have CST4 to 7 than men with only marital partners (CST4 to 7 prevalence ratio, 1.84; 95% confidence interval [CI], 1.16 to 2.92). Female partner Nugent BV is significantly associated with penile microbiota. Our data support the exchange of BV-associated bacteria through intercourse, which may explain BV recurrence and persistence.

Background International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. Methods We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15-49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population. Findings Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75•7% of the lakeside population and 16•2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13•7%] in inland and 2439 [40•1%] in fishing communities). 3878 (75•4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68•4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5•7% (95% credibility interval 4•4-7•3) of transmissions occurred within lakeside areas, 89•2% (86•0-91•8) within inland areas, 1•3% (0•6-2•6) from lakeside to inland areas, and 3•7% (2•3-5•8) from inland to lakeside areas. Interpretation Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics.