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Combination HIV prevention and treatment interventions (CHIs) have led to substantial declines in HIV incidence in sub-Saharan Africa; however, population-level data on non-HIV sexually transmitted infections (STIs) in the context of CHIs are rare. We aimed to assess STI burden following scale-up of CHIs in Uganda.The Sexually Transmitted Infection Prevalence Study (STIPS) was a cross-sectional study nested within a population-based cohort among inland agrarian and Lake Victoria fishing populations in southern Uganda. STIPS enrolled consenting residents aged 18-49 years in two communities (one inland and one fishing) between May and October, 2019, and measured the prevalence of chlamydia, gonorrhoea, trichomonas, syphilis, and herpes simplex virus 2 (HSV-2).Between May 27, 2019 and Oct 25, 2019, STIPS enrolled 1825 participants. HIV prevalence was 14·0% among the inland population and 39·8% among the fishing population, with about 90% HIV viral load suppression in both communities. Among inland and fishing populations, chlamydia prevalence was 9·6% (95% CI 7·9-11·7) and 9·9% (8·1-12·0), gonorrhoea prevalence 5·0% (3·8-6·7) and 8·4% (6·8-10·5), trichomonas prevalence 9·4% (7·7-11·5) and 12·2% (10·2-14·5), and HSV-2 prevalence 43·0% (39·9-46·3) and 64·4% (61·3-67·6), respectively. In the fishing population, syphilis seropositivity was 24·2% (21·5-27·2) with 9·4% (7·7-11·5) having high-titre (rapid plasma reagin ≥1:8) infection, including 16·9% (11·9-24·0%) of men living with HIV. Prevalence of at least one curable STI (chlamydia, gonorrhoea, trichomonas, or high-titre syphilis) was 51% higher among people living with HIV (vs HIV negative; adjusted prevalence risk ratio [PRR] 1·51; 95% CI 1·27-1·78), including among pregnant women (adjusted PRR 1·87, 1·11-3·17), with no differences by HIV suppression status.Despite near universal HIV treatment, STI burden remains extremely high in southern Uganda, particularly among people living with HIV. There is an urgent need to integrate STI care with HIV services in African settings.National Institutes of Health.

BackgroundLongitudinal population-based cohorts are critical in HIV surveillance programs in Africa but continued rapid population growth poses serious challenges to maintaining cohort representativeness with limited resources. In one such cohort, we evaluated if systematic exclusion of some residents due to growing population size biases key HIV metrics like prevalence and viremia.MethodsData were obtained from the Rakai Community Cohort study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. We evaluated the extent to which changing inclusion criteria may bias recent population HIV seroprevalence and viremia estimates from the RCCS using ensemble machine learning models fit to 2019-2020 RCCS census and survey data.ResultsOf the 24,729 census-eligible residents, 2,920 (12%) were living within new household structures and excluded. Predicted seroprevalence for excluded residents was 11.4% (95% Confidence Interval: 10.2, 12.3) compared to 11.8% in the observed sample. However, predicted seroprevalence for younger excluded residents 15-24 years was 5.1% (3.6, 6.1), which was significantly higher than that in the observed sample for the same age group (2.6%). Over all ages, predicted prevalence of viremia in excluded residents (2.8% [2.2, 3.3]) was higher than that in the observed sample (1.7%), resulting in a somewhat higher overall population viremia estimate of 1.9% [1.8, 2.0]).ConclusionsExclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall HIV seroprevalence estimates were not significantly affected.Key messages (3-5)In-migrants in the observed sample in the RCCS surveillance area differ from currently excluded in-migrants on various demographic characteristics.Machine learning methods may be useful tools in estimating biases introduced by the systematic exclusion of populations for which we have some data.In the context of rapid population growth, population-based open cohorts in sub-Saharan Africa must prioritize limited resources while ensuring HIV estimates are representative of the population.FundingFunding for this project was supported by the National Institute of Allergy and Infectious Diseases (R01AI143333 and R01AI155080) and the National Institute of Mental Health (R01MH115799). The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the funding agencies.Research by Aleya Khalifa reported in this publication was supported by the National Institute of Allergy And Infectious Diseases (T32AI114398). Larry Chang was supported by the National Heart, Lung, and Blood Institute (R01HL152813), Fogarty International Center (D43TW010557) and the Johns Hopkins University Center for AIDS Research (P30AI094189). Susie Hoffman and John Santelli were supported by the U.S. National Institute of Child Health and Human Development (NICHD) (R01HD091003; Santelli, PI). Susie Hoffman was also supported by the National Institute of Mental Health (P30-MH43520; Remien, PI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Ethics approvalThis study was approved by the Uganda National Council for Science and Technology (approval number HS 540), the Uganda Virus Research Institution Research and Ethics Committee (approval number GC/127/08/12/137), Johns Hopkins Institutional Review Board (approval number IRB-00217467), and the Columbia University Institutional Review Board (approval number IRB-AAAR5428).

IntroductionCertain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including bar work and transportation. However, data on changes in prevalence of untreated HIV infection and HIV incidence within occupations following rollout of antiretroviral therapy and voluntary medical male circumcision programs in 2004 are limited.MethodsWe evaluated 12 rounds of survey data collected between 1999-2016, from the Rakai Community Cohort Study, a population-based study of adolescents and adults 15-49 years in Uganda, to assess changes in the prevalence of untreated HIV infection and incidence by self-reported primary occupation. Adjusted prevalence risk ratios (adjPRR) for untreated HIV and incidence rate ratios for HIV incidence with 95% confidence intervals (CIs) were estimated using Poisson regression. Primary outcomes were stratified by gender and HIV incidence compared over three time periods (1999-2004; 2005-2011; 2011-2016) representing, respectively, the period prior to scale up of combined HIV prevention and treatment, the scale up period, and full implementation.Results33,866 individuals, including 19,113 (56%) women participated. Of these participants, 17,840 women and 14,244 men who were HIV-negative at their first study visit contributed 57,912 and 49,403 person-years of follow-up, respectively. Agriculture was the most common occupation at all study visits, though its prevalence declined from 39 to 29% among men and from 61 to 40% among women between 1999 and 2016. Untreated HIV infection substantially declined between 1999 and 2016 across most occupational subgroups, including by 70% among men (12 to 4.2%; adjPRR=0.30; 95%CI:0.23-0.41) and by 78% among women working in agriculture (14.7 to 4.0%; adjPRR=0.22; 95%CI:0.18-0.27), along with increasing antiretroviral therapy coverage. Exceptions included men working in transportation and women working in tailoring/laundry services. HIV incidence declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers or men working in transportation.ConclusionUntreated HIV infection and HIV incidence have declined in most occupational sub-groups in Rakai, Uganda. However, women working in bars and restaurants and men working in transportation continue to have relatively high burden of untreated HIV and HIV incidence, and as such should be considered key priority populations for targeted HIV programming.

To improve timely access to quality HIV research data, the Rakai Health Sciences Program (RHSP) Data Mart was developed to store cohort study data from a legacy database platform in a modernized system using standard data management processes. The RHSP Data Mart was developed on a Microsoft SQL Server platform using Microsoft SQL Server Integration Services with custom data mappings and queries. The data mart stores 20+ years of longitudinal HIV research data and includes standard processes for managing data, data dictionary, training materials, and a library of queries to fulfill data requests and load new data from completed survey rounds. The RHSP Data Mart enables efficient querying and analysis of multidimensional research data by simplifying data integration and processing. A sustainable database platform with well-defined data management processes promotes data accessibility and reproducibility, enabling researchers to advance their understanding and management of infectious diseases.

Background The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President’s Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. Methods A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men. Results A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21–35 years) to 22 years (IQR, 18–29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28–.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. Conclusions VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

PURPOSE: Antiretroviral therapy reduced infectious eye diseases (EDs) in HIV infected people. There is limited data on age-related EDs and visual impairment (VI) in people living with HIV. We report prevalence of VI and spectrum of EDs in HIV infected people in an ART era in Rakai, Uganda. METHODS: A philanthropic campaign during 2009-2012 provided ophthalmic services to HIV+ patients in care. Unilateral presenting visual acuity (VA) was assessed by a trained staff in HIV clinics using a 6-meter Snellen chart. A slit lamp examination by an ophthalmologist evaluated eyes with impaired acuity. A retrospective chart review was later conducted retrieving data of patients participating the ophthalmic service. VI was defined referencing WHO’s ICD-11. Ophthalmic diagnosis was summarized by VI level. Logistic regressions estimated demographic associations with cataract diagnosis. RESULTS: 688 HIV+ patients were evaluated, median age was 44 (IQR: 37-50) years, 69% were female. 51% were on ART (median duration 4, IQR: 2-5 years). Crude prevalence of moderate/severe VI and blindness were both 2%. The main diagnoses were refractive error (55%), conjunctivitis (18%), cataract (15%), and pterygium (11%). Cataract prevalences were 10%, 12% and 26% among age groups of 19-34, 35-49 and ≥ 50 years, respectively. Cataract was found in 73% of the HIV+s with blindness and in 63% of those with moderate/severe VI. Older age and male sex were significantly associated with higher cataract prevalence. CONCLUSION: VI in HIV+ patients in Rakai was mainly due to refractive error and cataract. Cataract was common in all age groups.

The foreskin is a site of heterosexual acquisition of HIV-1 among uncircumcised men. However, some men remain HIV-negative despite repeated, unprotected vaginal intercourse with HIV-positive partners, while others become infected after few exposures. The foreskin microbiome includes a diverse group of anaerobic bacteria that have been linked to HIV acquisition. However, these anaerobes tend to coassociate, making it difficult to determine which species might increase HIV risk and which may be innocent bystanders. Here, we show that 6 specific anaerobic bacterial species, Peptostreptococcus anaerobius, Prevotella bivia, Prevotella disiens, Dialister propionicifaciens, Dialister micraerophilus, and a genetic near neighbor of Dialister succinatiphilus, significantly increased cytokine production, recruited HIV-susceptible CD4+ T cells to the inner foreskin, and were associated with HIV acquisition. This strongly suggests that the penile microbiome increases host susceptibility to HIV and that these species are potential targets for microbiome-based prevention strategies.

Objectives Since incivility is linked to adverse effects in patient care and health care worker well‐being, evaluation of the prevalence of incivility during the formative years of residency training is warranted. The aim of this study was to determine the perceived presence and degree of incivility between emergency medicine (EM) and ophthalmology residents during emergency department (ED) consultations. Methods We conducted a single‐site, survey‐based study, targeted to ophthalmology and EM residents. The survey we distributed included questions adapted from validated and widely used surveys measuring incivility in the workplace (Workplace Incivility Scale) and incivility within the ED. Results Ophthalmology (13/15, 86.7%) and EM (42/48, 87.5%) residents participated, with an overall response rate of 55 of 63 (87.3%). Most residents (47/55, 85.5%) reported some degree of incivility during consultations, with a greater proportion of females reporting incivility (100%) than males (77.4%, p = 0.033). A total of 52.7% of respondents reported occurrence of incivility on a quarterly basis; 21.8% reported monthly, 10.9% weekly, and none daily. Incivilities were reported most commonly during nonurgent consults (85.5%). The two most common incivilities reported by trainees were when the other party paid little attention to their statements or opinions (80% of residents) or doubted their professional judgment (74.5% of residents). More female trainees reported jokes being told at their expense compared to males (15.8% vs. 0%, p = 0.049). Residents most often attributed incivility to stress (78.2%), loss of empathy/burnout (63.6%), or attempts to shift responsibility to another party (60.0%). Among EM residents surveyed, incivility was identified as occurring most often during consultations with surgical specialties. Conclusions Incivility during interdepartmental consultations between EM and ophthalmology is commonly reported by physicians‐in‐training. It occurs more often during consultations deemed as nonurgent and is more commonly reported by females. Given its associations with adverse outcomes, interventions to decrease incivility early in training may be warranted.

Background There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa. Methods Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression. Results There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15–29 vs 40–49 years; adjRR = 1.80; 95% CI = 1.19–2.71), male sex (adjRR = 2.09, 95% CI = 1.47–2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34–2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34–2.73) were factors associated with persistent viremia. Conclusions Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.

International audience; 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.Funding: The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

Background Intimate partner violence (IPV), HIV and sexually transmitted infections (STI) can contribute to disparities in population health, depending on the individual, social and environmental factors characterizing a setting. To better understand the place-based determinants and patterns of these key interrelated public health problems in Uganda, we compared risk factors for IPV, HIV and STI in fishing, trading and agrarian communities in Rakai, Uganda by gender. Method This study used cross-sectional data collected from 14,464 sexually active men (n = 6531) and women (n = 7933) as part of the Rakai Community Cohort Study, a population-based open cohort study of men and women aged 15–49 years. We used multilevel modified poisson regression models, which incorporated random intercepts for community and households. Factors associated with IPV, HIV and STI were assessed separately for men and women in fishing, trading and agrarian communities. Results A larger proportion of participants in the fishing communities than those in trading and agrarian communities were HIV positive, engaged in HIV risk behaviors, had STI symptoms and reported perpetration of or victimization by IPV. Female gender was a shared correlate of IPV, HIV and STI in the fishing communities. Engagement in multiple sexual relationships or partner’s engagement in multiple relationships were shared correlates of IPV, and HIV in agrarian communities and IPV and STI in trading communities. Conclusion Programs should target factors at multiple levels to reduce risk for syndemic conditions of HIV, STI and IPV in Rakai, Uganda particularly among men and women in fishing communities.

The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 copies/mL is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Sera from persons seen in two surveys (2008–2009 and 2012–2013) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0%, was compared with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95% confidence interval (CI) 0.90–1.23] in 2008–2009 and 0.66/100 py (95% CI 0.52–0.83) in 2012–2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95% CI 0.97–2.30) in 2008–2009 and 2.55/100 py (95% CI 1.51–3.59) in 2012–2013 (a significant increase, p

Background Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called “Health Scouts” to promote engagement in HIV treatment and prevention services. Methods and findings The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (, Larry Chang and co-workers study an intervention by which community health workers aim to promote engagement in HIV treatment and prevention services in Uganda., Author summary Why was this study done? HIV remains a major global cause of morbidity and mortality. Some communities have very high levels of HIV infection. These hyperendemic communities may benefit from new strategies to better implement proven HIV treatment and prevention services. A client-centered and mobile phone application-supported counseling approach used by community health workers may be a new strategy to improve the uptake of HIV treatment and prevention services in these settings. What did the researchers do and find? We conducted a cluster randomized controlled trial to evaluate the effectiveness of a new community health worker strategy to improve HIV services uptake in a hyperendemic community in Uganda. These community health workers were deployed in this community for about 3 years. We compared outcomes in clusters randomized to community health workers with clusters randomized to not having community health workers. We found that residents in areas, which had the community health workers, were more likely to be in HIV care and to be on antiretroviral therapy. We found no significant changes in HIV viral suppression or male circumcision coverage. What do these findings mean? These findings suggest that this novel community health worker approach may be a useful strategy to help people living with HIV engage in care and get effective treatment. This type of intervention may contribute to controlling HIV in settings with high HIV burden.

ObjectivesWe assessed the association between intimate partner violence (IPV) and union disruption (divorce or separation) in the rural Ugandan setting of Rakai District.MethodsWe analyzed longitudinal data collected from April 1999 to June 2006, from 6834 women (15-49 years) living in 50 communities in Rakai. Participants were either officially married, traditionally married or in a consensual union during one or more surveys and completed at least one follow-up survey. The primary outcome was union disruption through divorce or separation from the primary sexual partner.ResultsPast year IPV ranged from 6.49 % (severe physical abuse) to 31.99 % (emotional abuse). Severe physical IPV was significantly associated with divorce/separation, after adjusting for other covariates (aOR = 1.80, 95 % CI 1.01-3.22). Another predictor of union disruption was a woman having two or more sexual partners in the past year (aOR = 8.42, 95 % CI 5.97-11.89). Factors protecting against divorce/separation included an increasing number of co-resident biological children and longer duration of union.ConclusionsIPV, particularly severe physical abuse, is an important risk factor for union disruption. Marital counseling, health education and interventions should address the role of IPV on the wellbeing of women and the stability of couples in Uganda.

BackgroundIndeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and its sociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda.Methods115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15-49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results.ResultsThe prevalence of HIV serologically indeterminate results was 4.9%. Indeterminate results were less likely among women than men (adjPR 0.76, 95% CI 0.71,0.81), in unmarried participants than married participants (adjPR 0.92, 95% CI 0.85,99), and in individuals with primary (adjPR 0.90, 95% CI 0.80,1.02), secondary (adjPR 0.83, 95% CI 0.73,0.96) and post-secondary (adjPR 0.75, 95% CI 0.60,0.94) education, relative to no education. The proportions of persons with indeterminate results progressing to HIV positive, negative or indeterminate results in subsequent visits was 5%, 71% and 24%, respectively.ConclusionHIV serologically indeterminate results were associated with gender and marital status. HIV surveillance programs should develop a protocol for reporting individuals with mixed or persistently indeterminate HIV results on multiple follow-up visits. Most indeterminate results became HIV-negative over time, but follow-up is still needed to detect positive serologies.

ObjectiveMale circumcision (MC) reduces acquisition of HIV-1 in heterosexual men by at least 60%, but the biological mechanism for this protection is incompletely understood. Previous studies have shown that a larger foreskin size, increased abundance of anaerobic bacteria in the sub-preputial space, and higher levels of pro-inflammatory cytokines on the penis are all prospectively associated with risk of HIV-1 acquisition. Since coverage of the glans on the non-erect penis is dependent on foreskin size, a larger foreskin could result in a less aerobic environment that might preferentially support anaerobic bacterial growth and induce inflammation. We therefore assessed the relationship between foreskin size, penile microbiome composition and local inflammation.MethodsThis is a retrospective, cross-sectional analysis of 82 HIV-uninfected men who participated in a randomized trial of MC for HIV-1 prevention in Rakai, Uganda between 2003-2006. Sub-preputial swabs were collected prior to MC and assessed for cytokines (multiplexed immunosorbent assay) and bacterial load (qPCR) and taxon abundance (sequencing). Foreskin size was measured immediately after MC.ResultsForeskin surface area did not correlate with total bacterial load (rho = 0.05) nor the abundance of key taxa of bacteria previously associated with HIV-1 risk (rho = 0.04-0.25). Foreskin surface area also did not correlate with sub-preputial cytokine concentrations previously associated with HIV-1 risk (IL-8 rho = 0.05).ConclusionsLarger foreskin size is not associated with either increased penile anaerobes or pro-inflammatory cytokines. These data suggest that foreskin size does not increase HIV-1 risk through changes in penile microbiome composition or penile inflammation.

HIV-1 subtype and viral load set point have been implicated as strong predictors of HIV-1 disease progression; however, the relationship between these two variables has not been investigated. We used data from the Rakai Community Cohort Study to investigate whether the association between viral load set point and disease progression is modified by HIV subtype. Time to AIDS or AIDS-related death was estimated by Kaplan–Meier survival analysis stratified by subtype and viral set point, and Cox proportional hazards regression with an interaction term between viral load set point and HIV subtype. The interaction term did not indicate effect measure modification between viral load set point and progression to AIDS by HIV-1 subtype [adjusted hazard ratio (aHR), 0.99; 95% confidence interval (CI) 0.61–1.61; p = .968]. Stratifed analysis by subtype was also not indicative of a difference in relationship between viral load set point and time to AIDS with overlapping 95% CIs between subtypes A and D (subtype A aHR: 2.40, 95% CI 1.45–3.99, subtype D aHR: 1.96, 95% CI 1.60–2.40). These results indicate that the higher mortality in subtype D-infected individuals is independent of viral load set point.

HIV prevalence varies markedly throughout Africa, and it is often presumed areas of higher HIV prevalence (i.e., hotspots) serve as sources of infection to neighboring areas of lower prevalence. However, the small-scale geography of migration networks and movement of HIV-positive individuals between communities is poorly understood. Here, we use population-based data from ~22,000 persons of known HIV status to characterize migratory patterns and their relationship to HIV among 38 communities in Rakai, Uganda with HIV prevalence ranging from 9 to 43%. We find that migrants moving into hotspots had significantly higher HIV prevalence than migrants moving elsewhere, but out-migration from hotspots was geographically dispersed, contributing minimally to HIV burden in destination locations. Our results challenge the assumption that high prevalence hotspots are drivers of transmission in regional epidemics, instead suggesting that migrants with high HIV prevalence, particularly women, selectively migrate to these areas., HIV prevalence varies throughout Africa, but the contribution of migration remains unclear. Using population-based data from ~22,000 persons, Grabowski et al. show that HIV-positive migrants selectively migrate to high prevalence areas and that out-migrants from these areas geographically disperse.

OBJECTIVE To assess geospatial patterns of HIV antiretroviral therapy (ART) treatment facility use and whether they were impacted by viral load suppression. METHODS We extracted data on the location and type of care services utilized by HIV-positive persons accessing ART between February 2015 and September 2016 from the Rakai Community Cohort Study in Uganda. The distance from Rakai Community Cohort Study households to facilities offering ART was calculated using the open street map road network. Modified Poisson regression was used to identify predictors of distance traveled and, for those traveling beyond their nearest facility, the probability of accessing services from a tertiary care facility. RESULTS In total, 1554 HIV-positive participants were identified, of whom 68% had initiated ART. The median distance from households to the nearest ART facility was 3.10 km (interquartile range, 1.65-5.05), but the median distance traveled was 5.26 km (interquartile range, 3.00-10.03, P

Summary Background Intimate partner violence (IPV) is associated with HIV infection. We aimed to assess whether provision of a combination of IPV prevention and HIV services would reduce IPV and HIV incidence in individuals enrolled in the Rakai Community Cohort Study (RCCS), Rakai, Uganda. Methods We used pre-existing clusters of communities randomised as part of a previous family planning trial in this cohort. Four intervention group clusters from the previous trial were provided standard of care HIV services plus a community-level mobilisation intervention to change attitudes, social norms, and behaviours related to IPV, and a screening and brief intervention to promote safe HIV disclosure and risk reduction in women seeking HIV counselling and testing services (the Safe Homes and Respect for Everyone [SHARE] Project). Seven control group clusters (including two intervention groups from the original trial) received only standard of care HIV services. Investigators for the RCCS did a baseline survey between February, 2005, and June, 2006, and two follow-up surveys between August, 2006, and April, 2008, and June, 2008, and December, 2009. Our primary endpoints were self-reported experience and perpetration of past year IPV (emotional, physical, and sexual) and laboratory-based diagnosis of HIV incidence in the study population. We used Poisson multivariable regression to estimate adjusted prevalence risk ratios (aPRR) of IPV, and adjusted incidence rate ratios (aIRR) of HIV acquisition. This study was registered with ClinicalTrials.gov, number NCT02050763. Findings Between Feb 15, 2005, and June 30, 2006, we enrolled 11 448 individuals aged 15–49 years. 5337 individuals (in four intervention clusters) were allocated into the SHARE plus HIV services group and 6111 individuals (in seven control clusters) were allocated into the HIV services only group. Compared with control groups, individuals in the SHARE intervention groups had fewer self-reports of past-year physical IPV (346 [16%] of 2127 responders in control groups vs 217 [12%] of 1812 responders in intervention groups; aPRR 0·79, 95% CI 0·67–0·92) and sexual IPV (261 [13%] of 2038 vs 167 [10%] of 1737; 0·80, 0·67–0·97). Incidence of emotional IPV did not differ (409 [20%] of 2039 vs 311 [18%] of 1737; 0·91, 0·79–1·04). SHARE had no effect on male-reported IPV perpetration. At follow-up 2 (after about 35 months) the intervention was associated with a reduction in HIV incidence (1·15 cases per 100 person-years in control vs 0·87 cases per 100 person-years in intervention group; aIRR 0·67, 95% CI 0·46–0·97, p=0·0362). Interpretation SHARE could reduce some forms of IPV towards women and overall HIV incidence, possibly through a reduction in forced sex and increased disclosure of HIV results. Findings from this study should inform future work toward HIV prevention, treatment, and care, and SHARE's ecological approach could be adopted, at least partly, as a standard of care for other HIV programmes in sub-Saharan Africa. Funding Bill & Melinda Gates Foundation, US National Institutes of Health, WHO, President's Emergency Plan for AIDS Relief, Fogarty International Center.

Introduction: To assess progress towards the UNAIDS 90–90–90 initiative targets, we examined the HIV care cascade in the population-based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub-groups. Methods: Self-reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a χ2 test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART). Results: From September 2013 through December 2015, 3,666 HIV-positive participants were identified in the RCCS. As of December 2015, 98% had received HIV Counseling and Testing (HCT), 74% were enrolled in HIV care, and 63% had initiated ART of whom 92% were virally suppressed after 12 months on ART. Engagement in care was lower among men than women (enrolment in care: adjPRR 0.84, 95% CI 0.77–0.91; ART initiation: adjPRR 0.75, 95% CI 0.69–0.82), persons aged 15–24 compared to those aged 30–39 (enrolment: adjPRR 0.72, 95% CI 0.63–0.82; ART: adjPRR 0.69, 95%CI 0.60–0.80), unmarried persons (enrolment: adjPRR 0.84, 95% CI 0.71–0.99; ART adjPRR 0.80, 95% CI 0.66–0.95), and new in-migrants (enrolment: adjPRR 0.75, 95% CI 0.67–0.83; ART: adjPRR 0.76, 95% CI 0.67–0.85). This cohort achieved 98–65–92 towards the UNAIDS “90–90–90” targets with an estimated 58% of the entire HIV-positive RCCS population virally suppressed. Conclusions: This cohort achieved over 90% in both HCT and viral suppression among ART users, but only 65% in initiating ART, likely due to both an ART eligibility criterion of

We assessed medical male circumcision (MMC) scale-up in Rakai, Uganda using population-based surveys during 2007-2014. MMC coverage increased from 28.5 to 52.0%. Coverage was initially lower in 15-19-year-olds but increased in 2014, was higher in married men and in trading communities, and lowest in the sexually inactive. Coverage did not vary by self-perceived risk of HIV or HIV serostatus. Increasing generalized coverage suggested that MMC became normative, but coverage falls short of WHO/Joint United Nations Programme on HIV and AIDS (UNAIDS) 80% targets, indicating the need for demand generation.

We assessed medical male circumcision (MMC) coverage and knowledge and attitudes toward MMC adoption in men in Rakai, Uganda after 4 years of scale-up. MMC prevalence only reached 28 %, with an annual increase of 4 %. Prevalence was lower in men not using condoms or having never received HIV testing and counseling. Over 95 % of uncircumcised men knew the health benefits of and places offering MMC, but only 27 % were willing to adopt MMC. Main reasons for non-acceptance were fear of pain or injury. The data suggest MMC uptake in Rakai has been suboptimal and demand generation is key for scale-up.

Importance Medical male circumcision (MMC) and antiretroviral therapy (ART) are proven HIV prevention interventions, but there are limited data on the population-level effect of scale-up of these interventions in sub-Saharan Africa. Such evaluation is important for planning and resource allocation. Objective To examine whether increasing community MMC and ART coverage was associated with reduced community HIV incidence in Rakai District, Uganda. Design, Setting, and Participants Using person-level data from population-based surveys conducted from 1999 through 2013 in 45 rural Rakai communities, community-level ART and MMC coverage, sociodemographics, sexual behaviors, and HIV prevalence and incidence were estimated in 3 periods: prior to the availability of ART and MMC (1999-2004), during early availability of ART and MMC (2004-2007), and during mature program scale-up (2007-2013). Exposures Community MMC coverage in males and ART coverage in HIV-positive persons of the opposite sex based on self-reported MMC status and ART use. Main Outcomes and Measures Adjusted incidence rate ratios (IRRs) for sex-specific community HIV incidence estimated using multivariable Poisson regression with generalized estimating equations. Results From 1999 through 2013, 44 688 persons participated in 1 or more surveys (mean age at the first survey, 24.6 years [range, 15-49]; female, 56.5%; mean survey participation rate, 92.6% [95% CI, 92.4%-92.7%]). Median community MMC coverage increased from 19% to 39%, and median community ART coverage rose from 0% to 21% in males and from 0% to 26% in females. Median community HIV incidence declined from 1.25 to 0.84 per 100 person-years in males, and from 1.25 to 0.99 per 100 person-years in females. Among males, each 10% increase in community MMC coverage was associated with an adjusted IRR of 0.87 (95% CI, 0.82-0.93). Comparing communities with MMC coverage more than 40% (mean male community incidence, 1.03 per 100 person-years) with communities with coverage of 10% or less (mean male incidence, 1.69 per 100 person-years), the adjusted IRR was 0.61 (95% CI, 0.43-0.88). For each 10% increase in female self-reported ART coverage, there was no significant reduction in male HIV incidence (adjusted IRR, 0.95 [95% CI, 0.81-1.13]). Comparing communities with female ART coverage more than 20% (mean male incidence, 0.87 per 100 person-years) to communities with female ART coverage of 20% or less (mean male incidence, 1.17 per 100 person-years), the adjusted IRR was 0.77 (95% CI, 0.61-0.98). Neither MMC nor male ART coverage was associated with lower female community HIV incidence. Conclusions and Relevance In Rakai, Uganda, increasing community MMC and female ART coverage was associated with lower community HIV incidence in males. If similar associations are found elsewhere, this would support further scale-up of MMC and ART for HIV prevention in sub-Saharan Africa.

Background: We used self-administered vaginal swabs to assess the incidence and clearance of carcinogenic human papillomavirus (HPV) infections in rural Rakai, Uganda. Methods: Women provided self-administered vaginal swab at annual home-based visits. Type-specific carcinogenic HPV incidence and clearance and risk factors were assessed. Results: Carcinogenic HPV incidence was 17.3 per 100 person-years among HIV-positive women compared with 7.0 per 100 person-years among HIV-negative women (P < 0.001). HPV-51 had the highest incidence followed by HPV-16 (1.8 per 100 and 1.5 per 100 person-years, respectively). In multivariate model, HIV-positive women were twice as likely to have incident infection compared with HIV-negative women. Younger women were at higher risk for incident infection, as were women with higher lifetime and recent sexual partners, and high perception of AIDS. Married women were less likely to have incident infection. Approximately half of all carcinogenic HPV infections cleared over the study follow-up of 3 years. HPV-31, HPV-35, and HPV-16 had the lowest clearance (16.7%, 27.9%, and 38.3%, respectively). In multivariate model, HIV-positive, women over 30 years with higher HPV viral, burden and more lifetime sex partners were less likely to clear infections. Conclusions: Self-collected vaginal swabs provide accurate HPV exposure assessment for studying HPV exposure and epidemiology and can be an important tool for research in populations unwilling to undergo pelvic exam. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1300–7)

The objective of this study was to compare human papillomavirus (HPV) DNA testing between self-administered vaginal swabs and physician-administered cervical swabs in women from rural Rakai District Uganda. Between 2002 and 2003 women from a population-based cohort participated in an HPV study. Women collected self-administered vaginal swabs and were also offered a pelvic examination which included physician-collected cervical samples. Methods: Hybrid-capture 2 was used to determine carcinogenic HPV status. Polymerase chain reaction was used to determine HPV genotypes. Unweighted k statistics were used to determine agreement. Compliance with self-collected swabs was greater than or equal to 86%; however only 51% accepted a pelvic examination. Carcinogenic HPV prevalence was 19% in self-collected and 19% in physician-collected samples. Agreement among paired observations was 92% with a k of 0.75. Kappa between self- and physician-collected samples was similar in HIV strata (k = 0.71 and 0.75 for HIV-positive and HIV-negative respectively). In this community-based setting detection of carcinogenic HPV was comparable among self- and physician-administered samples. Self-collection is a feasible and accurate means of obtaining HPV samples from women in resource-poor settings or persons reluctant to undergo a pelvic examination. (authors)

Background: A decade after the rollout of antiretroviral therapy (ART) in sub-Saharan Africa the effects of this structural change on social aspects of HIV such as rates of HIV disclosure to partners remain largely unmeasured. We evaluated whether the introduction of ART was associated with disclosure of HIV diagnosis to spouses in Rakai Uganda using longitudinal population-based data. Methods: We identified individuals in marital / cohabitating unions who were newly diagnosed with HIV in Rakai Community Cohort Study (RCCS) surveys between 2000 and 2008 where antiretroviral therapy (ART) was introduced in mid-2004. Using discrete-time survival analysis we assessed the hazard of self-reported HIV disclosure to spouse after diagnosis pre- and post-ART rollout adjusting for individual and union characteristics. Disclosure in the ART period was further stratified by ART initiation. Results: The analysis included 557 married adults 264 of whom were diagnosed with HIV before ART was available (2000-2004) and 293 diagnosed after ART was introduced (2005-2008). The cumulative incidence of self-reported disclosure rounds was 75.2% in the post-ART period compared to 58.3% before ART availability (p

We assessed whether women had accurate knowledge of their partners' male circumcision status using survey data (2010-2011) from Rakai, Uganda, and examined characteristics of women who misreported male circumcision status. Among couples in which men were uncircumcised (n = 1744), 8.2% women misreported; and among couples in which men were confirmed circumcised (n = 759), 1.2% women misreported. Younger women were 2.2 times more likely to misreport compared with older women. Misreporting was not associated with other sociodemographics or behavioural characteristics. If women are to act as advocates for male circumcision acceptance, there is a need to educate women, particularly younger women about the nature and recognition of male circumcision.

Introduction : To assess progress towards the UNAIDS 90–90–90 initiative targets, we examined the HIV care cascade in the population-based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub-groups. Methods : Self-reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a χ 2 test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART). Results : From September 2013 through December 2015, 3,666 HIV-positive participants were identified in the RCCS. As of December 2015, 98% had received HIV Counseling and Testing (HCT), 74% were enrolled in HIV care, and 63% had initiated ART of whom 92% were virally suppressed after 12 months on ART. Engagement in care was lower among men than women (enrolment in care: adjPRR 0.84, 95% CI 0.77–0.91; ART initiation: adjPRR 0.75, 95% CI 0.69–0.82), persons aged 15–24 compared to those aged 30–39 (enrolment: adjPRR 0.72, 95% CI 0.63–0.82; ART: adjPRR 0.69, 95%CI 0.60–0.80), unmarried persons (enrolment: adjPRR 0.84, 95% CI 0.71–0.99; ART adjPRR 0.80, 95% CI 0.66–0.95), and new in-migrants (enrolment: adjPRR 0.75, 95% CI 0.67–0.83; ART: adjPRR 0.76, 95% CI 0.67–0.85). This cohort achieved 98–65–92 towards the UNAIDS “90–90–90” targets with an estimated 58% of the entire HIV-positive RCCS population virally suppressed. Conclusions : This cohort achieved over 90% in both HCT and viral suppression among ART users, but only 65% in initiating ART, likely due to both an ART eligibility criterion of