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Redefining viral load suppression (VLS) using lower cutpoints could impact progress towards the United Nations Programme on HIV/AIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 'third 95' in the Rakai Community Cohort Study. Population VLS would fall from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from <1000 to <200 and <50 copies/ml. The fraction of viremic persons increased by 17% after lowering the VLS cutpoint from <1000 to <200 copies/ml., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the relationship between household wealth and HIV incidence in rural Uganda over time from 1994 to 2018. In research conducted early in the epidemic, greater wealth (i.e. higher socioeconomic status, SES) was associated with higher HIV prevalence in sub-Saharan Africa (SSA); this relationship reversed in some settings in later years., Design: Analysis of associations over time in a population-based open cohort of persons 15-49 years from 17 survey-rounds in 28 continuously followed communities of the Rakai Community Cohort Study (RCCS)., Methods: The RCCS sample averaged 8622 individuals and 5387 households per round. Principal components analysis was used to create a nine-item asset-based measure of household wealth. Poisson regression with generalized estimating equation (GEE) and exchangeable correlation structure was used to estimate HIV incidence rate ratios (IRRs) by SES quartile, survey-round, sex, and age group., Results: From 1994 to 2018, SES rose considerably, and HIV incidence declined from 1.45 to 0.40 per 100 person-years (IRR = 0.39, 95% CI = 0.32--0.47, P < 0.001). HIV incidence was similar by SES category in the initial survey intervals (1994-1997); however, higher SES groups showed greater declines in HIV incidence over time. Multivariable analyses showed significant associations between HIV incidence and SES (IRR = 0.55 for highest compared with lowest quartile, 95% CI = 0.45--0.66, P < 0.001) controlling for time, sex, and age group., Conclusion: Beyond the early years of the RCCS, higher SES was associated with lower HIV incidence and SES gradients widened over time. The poor, like other key populations, should be targeted for HIV prevention, including treatment as prevention., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

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 < 0.001) and 57% of individuals travelled further than their nearest facility for ART. Those with higher education and wealth were more likely to travel further. In total, 93% of persons on ART were virally suppressed, and there was no difference in the distance traveled to an ART facility between those with suppressed and unsuppressed viral loads (5.26 vs. 5.27 km, P = 0.650)., Conclusion: Distance traveled to HIV clinics was increased with higher socioeconomic status, suggesting that wealthier individuals exercise greater choice. However, distance traveled did not vary by those who were or were not virally suppressed.

Objective: To assess the validity of self-reported antiretroviral therapy use (ART) using population-based cohort data., Methods: Self-reported ART use and nonuse was compared with a validated laboratory assay in 557 HIV-positive participants in the Rakai Community Cohort Study surveyed between September and December 2011 in Rakai, Uganda. The study population included participants from seven communities, including one fishing community with high HIV prevalence (∼41%). ART use was assayed using liquid chromatography-tandem mass spectrometry, which detects 20 antiretroviral drugs. HIV viral load measurements were also obtained. Individuals with at least two antiretroviral drugs detected were considered to be using ART., Results: One hundred and fifty-three (27%) participants self-reported ART use of whom 148 (97%) had at least two antiretroviral drugs detected. There were at least two antiretroviral drugs detected in 11% (n = 44/404) of individuals with no self-reported ART use. Overall, the specificity of self-reported ART use was 99% (95% CI 97-100%) and the sensitivity was 77% (70-83%). Positive and negative predictive values were 97% (95% CI 93-99%) and 89% (95% CI 86-92%), respectively. Nondisclosure of ART use was significantly more common in younger persons (<30 years) and among those in trading occupations., Conclusion: Self-reported ART use has high specificity and moderate sensitivity providing reasonable, but conservative estimates of population-based ART use. There is more under-reporting of ART use among younger persons and traders suggesting a need for more research on barriers to self-reporting of ART use in these sub-groups.

Objectives: Sub-Saharan African countries have substantially scaled-up safe male circumcision (SMC) services. However, it is unclear whether services are reaching men most at risk of HIV and whether there is behavioral disinhibition after SMC. We compared characteristics of SMC acceptors and nonacceptors in Rakai, Uganda., Design: Cohort design., Methods: Through the Rakai Community Cohort Study, baseline characteristics of 587 non-Muslim men who subsequently accepted SMC were compared with those of 4907 uncircumcised non-Muslim men. Behaviors after SMC were compared with those of men who remained uncircumcised. Poisson multivariable regression was used to estimate adjusted prevalence rate ratios of behaviors in circumcised versus uncircumcised men., Results: At baseline (pre-SMC), men subsequently circumcised were younger (mean = 26.1 years), as compared with the uncircumcised (mean = 28.5 years, P < 0.001), more likely to live in urban areas (21.1 versus 12.4%, P < 0.001), less likely to have been currently or previously married (36.5 versus 45.8%, P < 0.001) and more likely to report multiple sexual partners (48.3 versus 41.6%, P = 0.05) and genital discharge (7.4 versus 4.4%, P = 0.03). At follow-up (post-SMC), behaviors and genital discharge did not differ between the groups. Genital ulcers were less reported among circumcised (6.8%) compared with uncircumcised men (10.5%; adjusted prevalence rate ratios = 0.60, 95% confidence interval = 0.42-0.87, P = 0.007)., Conclusion: In Rakai district, Uganda, the circumcision service program is attracting sexually active men at higher risk of HIV and we find no evidence of behavioral disinhibition following circumcision. The SMC program in this setting has the potential to reduce the HIV epidemic among men.

Objectives: To quantify the association between intimate partner violence (IPV) and incident HIV infection in women in the Rakai Community Cohort Study between 2000 and 2009., Design and Methods: Data were from the Rakai Community Cohort Study annual surveys between 2000 and 2009. Longitudinal data analysis was used to estimate the adjusted incidence rate ratio (IRR) of incident HIV associated with IPV in sexually active women aged 15-49 years, using a multivariable Poisson regression model with random effects. The population attributable fraction was calculated. Putative mediators were assessed using Baron and Kenny's criteria and the Sobel-Goodman test., Results: Women who had ever experienced IPV had an adjusted IRR of incident HIV infection of 1.55 (95% CI 1.25-1.94, P = 0.000), compared with women who had never experienced IPV. Risk of HIV infection tended to be greater for longer duration of IPV exposure and for women exposed to more severe and more frequent IPV. The adjusted population attributable fraction of incident HIV attributable to IPV was 22.2% (95% CI 12.5-30.4). There was no evidence that either condom use or number of sex partners in the past year mediated the relationship between IPV and HIV., Conclusion: IPV is associated with incident HIV infection in a population-based cohort in Uganda, although the adjusted population attributable fraction is modest. The prevention of IPV should be a public health priority, and could contribute to HIV prevention.

We determined HIV infections in the Rakai cohort before (82/9434) and after (131/13082) the availability of antiretroviral therapy (ART). The proportions of total HIV infections pre-ART and post-ART were 18.3% and 13.7%, respectively, among identifiable HIV-discordant couples, 23.2% and 26.0%, respectively, in concordant HIV-negative couples, 29.3% and 17.6% in married persons with unknown partner status, and 29.3% and 42.7% in the unmarried. Voluntary counseling and testing targeting discordant couples is unlikely to have a substantial impact in this setting.

Objective: To evaluate the impact of antiretroviral therapy (ART) on HIV-1 transmission rates among HIV-1 discordant couples in Rakai, Uganda., Design: Observational cohort study., Methods: HIV-1 discordant couples were retrospectively identified between 2004 and 2009. Study participants underwent annual screening for HIV-1 and were interviewed to evaluate risk behaviors. Participants were offered voluntary counseling and testing and provided with risk reduction counseling. Free ART was offered to participants with a CD4 cell count of 250 cells/μl or less or WHO stage IV disease. HIV-1 incidence and sexual risk behaviors were compared before and after the HIV-1-positive index partners started ART., Results: Two hundred and fifty HIV-1 discordant couples were followed between 2004 and 2009 and 32 HIV-1-positive partners initiated ART. Forty-two HIV-1 transmissions occurred over 459.4 person-years prior to ART initiation, incidence 9.2/100 person-years [95% confidence interval (CI) 6.59-12.36]. In 32 couples in which the HIV-1 index partners started ART, no HIV-1 transmissions occurred during 53.6 person-years. The 95% CI for the incidence rate difference was -11.91 to -6.38 (P = 0.0097). Couples reported more consistent condom use during ART use, but there was no significant difference in the number of sexual partners or other risk behaviors. Viral load was markedly reduced in persons on ART., Conclusion: HIV-1 transmission may be reduced among HIV-1 discordant couples after initiation of ART due to reductions in HIV-1 viral load and increased consistent condom use.

Objective: To assess the association between hormonal contraceptive use and HIV progression., Design: A retrospective analysis of 625 female HIV seroconverters from a Ugandan cohort study., Methods: Multivariate Cox regression analyses incorporating time-varying hormonal contraceptive exposure were used to estimate the adjusted hazard ratios of death, and a composite outcome of AIDS or death, associated with hormonal contraceptive use. Sensitivity analyses included lagging hormonal contraceptive exposure, varying comparison groups, and separately assessing effects of oral and injectable contraceptives., Results: A total of 27.5% of women reported ever using hormonal contraception. Of 625 women, 104 (16.6%) died and 291 (46.6%) progressed to AIDS or death during observation. Time-varying hormonal contraceptive use was not associated with an increased hazard of death as compared with nonuse of hormonal contraception (adjusted hazard ratio 0.76, 95% confidence interval 0.41-1.39, P = 0.37), and was associated with a significantly reduced hazard of progression to AIDS or death (adjusted hazard ratio 0.70, 95% confidence interval 0.50-0.97, P = 0.03). None of the sensitivity analyses suggested an adverse effect of hormonal contraception on HIV progression., Conclusion: Hormonal contraceptive use was not associated with faster progression to death, and was associated with a reduced hazard of progression to the composite outcome of AIDS or death.

Objective: To determine whether heterosexual transmission of HIV differs according to HIV-1 subtype., Design: A retrospective observational cohort., Methods: HIV-1 subtype effects on heterosexual HIV-1 transmission were determined among 268 HIV-discordant couples retrospectively identified from a population cohort in Rakai, Uganda. HIV-1 subtype (gag and gp41 sequencing and multiregion hybridization assay) and viral loads (reverse transcriptase PCR) were determined. Adjusted incidence rate ratios (adj IRR) of HIV transmission by subtype were estimated by multivariable Poisson regression adjusting for characteristics of index HIV-positive and HIV-negative partners., Results: Adjusting for index HIV-positive partners' age, viral load, stage of disease, genital ulcer disease, and HIV-negative partners' genital ulcer disease and nonuse of condoms, subtype A viruses were associated with a higher rate of transmission than subtype D [adj.IRR 1.98, 95% confidence interval (CI) 1.17-3.34], but no differences in transmission were observed between recombinant viruses and subtype D (aIRR 1.53, P = 0.25). Index-positive partners' age less than 30 years (adj.IRR 3.44, 95% CI 1.75-6.78) and viral load (adj.IRR 2.37, 95% CI 1.75-3.21), and index-negative partners' genital ulcer disease (adj.IRR 1.71, 95% CI 1.08-2.70) and nonuse of condoms (adj.IRR 1.94, 95% CI 1.15-3.28) were significant determinants of HIV transmission., Conclusion: In Rakai, Uganda, subtype A viruses have a significantly higher rate of heterosexual transmission than subtype D viruses. Differential subtype transmission efficiency may be important for HIV vaccine evaluation and could contribute to subtype-specific HIV epidemics in sub-Saharan Africa.

Introduction: Male circumcision reduces HIV acquisition in men. We assessed whether foreskin surface area was associated with HIV acquisition prior to circumcision., Methods: In two randomized trials of male circumcision, the surface area of the foreskin was measured after surgery using standardized procedures. Nine hundred and sixty-five initially HIV-negative men were enrolled in a community cohort who subsequently enrolled in the male circumcision trials, provided 3920.8 person-years of observation prior to circumcision. We estimated HIV incidence per 100 person-years prior to circumcision, associated with foreskin surface area categorized into quartiles., Results: Mean foreskin surface area was significantly higher among men who acquired HIV (43.3 cm2, standard error 2.1) compared with men who remained uninfected (36.8 cm, standard error 0.5, P = 0.01). HIV incidence was 0.80/100 person-years (8/994.9 person-years) for men with foreskin surface areas in the lowest quartile (< or =26.3 cm2), 0.92/100 person-years (9/975.3 person-years) with foreskin areas in the second quartile (26.4-35.0 cm2), 0.90/100 person-years (8/888.5 person-years) with foreskin area in the third quartile (35.2-45.5 cm2) and 2.48/100 person-years (23/926.8 person-years) in men with foreskin surfaces areas in the highest quartile (>45.6 cm2). Compared with men with foreskin surface areas in the lowest quartile, the adjusted incidence rate ratio of HIV acquisition was 2.37 (95% confidence interval 1.05-5.31) in men with the largest quartile of foreskin surface area., Conclusion: The risk of male HIV acquisition is increased among men with larger foreskin surface areas.

The ability of WHO clinical staging to predict CD4 cell counts of 200 cells/microl or less was evaluated among 1221 patients screened for antiretroviral therapy (ART). Sensitivity was 51% and specificity was 88%. The positive predictive value was 64% and the negative predictive value was 81%. Clinical criteria missed half the patients with CD4 cell counts of 200 cells/microl or less, highlighting the importance of CD4 cell measurements for the scale-up of ART provision in resource-limited settings.