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To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these 'source' populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8-28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.

The Safe Homes And Respect for Everyone (SHARE) intervention introduced an intimate partner violence (IPV) prevention approach into Rakai Health Sciences Program, an established HIV research and service organization in Uganda. A trial found exposure to SHARE was associated with reductions in IPV and HIV incidence. This mixed methods process evaluation was conducted between August 2007 and December 2009, with people living in SHARE intervention clusters, to assess awareness about/participation in SHARE, motivators and barriers to involvement, and perceptions of how SHARE contributed to behavior change. Surveys were conducted with 1407 Rakai Community Cohort Study participants. Qualitative interviews were conducted with 20 key informants. Most (77%) were aware of SHARE, among whom 73% participated in intervention activities. Two-thirds of those who participated in SHARE felt it influenced behavior change related to IPV. While some felt confident to take part in new IPV-focused activities of a well-established program, others were suspicious of SHARE's motivations, implying awareness raising is critical. Many activities appealed to the majority (e.g., community drama) while interest in some activities was limited to men (e.g., film shows), suggesting multiple intervention components is ideal for wide-reaching programming. The SHARE model offers a promising, acceptable approach for integrating IPV prevention into HIV and other established health programs in sub-Saharan Africa.

Background: Understanding the impact of natural disasters on the HIV epidemic in populations with high HIV burden is critical for the effective delivery of HIV control efforts. We assessed HIV risk behaviors, seroprevalence, and viral suppression in a high HIV prevalence Lake Victoria fishing community before and after COVID-19 emergence and lockdown and a severe lake flooding event, both of which occurred in 2020. Methods: We used data from the largest Lake Victoria fishing community in the Rakai Community Cohort Study, an open population-based HIV surveillance cohort in south-central Uganda. The data were collected both prior to (September-December 2018) and after (October-December 2021) COVID-19 emergence and a severe flooding event. Households impacted by flooding were identified via drone data and through consulting village community health workers. The entire study population was subject to extensive COVID-19-related lockdowns in the first half of 2020. Differences in HIV-related outcomes before and after COVID, and between residents of flooded and non-flooded households, were assessed using a difference-in-differences statistical modeling approach. Findings: A total of 1,226 people participated in the pre- and post-COVID surveys, of whom 506 (41%) were affected by flooding. HIV seroprevalence in the initial period was 37% in flooded and 36.8% in non-flooded households. After the COVID-19 pandemic and lockdown, we observed a decline in HIV-associated risk behaviors: transactional sex declined from 29.4% to 24.8% (p = 0.011), and inconsistent condom use with non-marital partners declined from 41.6% to 37% (p = 0.021). ART coverage increased from 91.6% to 97.2% (p<0.001). There was 17% decline in transactional sex (aPR = 0.83, 95% CI: 0.75–0.92) and 28% decline in the overall HIV risk score (aPR = 0.83, 95% CI: 0.75–0.92) among HIV-seronegative participants. We observed no statistically significant differences in changes of HIV risk behavior, seroprevalence, or viral suppression outcomes when comparing those affected by floods to those not affected by floods, in the periods before and after COVID-19, based on difference-in-differences analyses. Interpretation: Despite a high background burden of HIV, the COVID-19 pandemic, and severe flooding, we observed no adverse impact on HIV risk behaviors, seroprevalence, or virologic outcomes. This may be attributed to innovative HIV programming during the period and/or population resilience. Understanding exactly what HIV programs and personal or community-level strategies worked to maintain good public health outcomes despite extreme environmental and pandemic conditions may help improve HIV epidemic control during future natural disaster events. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess the association between cytomegalovirus (CMV) IgG antibody levels, HIV disease progression, and immune activation markers.DesignA prospective cohort study was conducted among women enrolled in a trial that was designed to determine the effect of acyclovir on HIV disease progression in Rakai, Uganda.MethodsThe primary endpoints were progression to a CD4 T-cell count less than 250 cells/μl, nontraumatic death, or initiation of antiretroviral therapy (ART). CD4 T-cell counts, HIV viral load, C-reactive protein (CRP), and soluble CD14 levels were assessed biannually for 24 months. CMV IgG antibodies were measured at baseline among all women and annually among a subset of women who initiated ART.ResultsThere were 300 HIV/CMV-coinfected participants who contributed a total of 426.4 person-years with a median follow-up time of 1.81 years. Compared with the lowest CMV IgG tertile group at baseline, the highest CMV IgG tertile group was associated with an increased risk to reach a primary endpoint independent of acyclovir use, age, CD4 T-cell count, and HIV viral load at baseline [adjusted hazard ratio = 1.59; (95% CI = 1.05-2.39); P = 0.027]. Among pre-ART visits (n = 1200), women in the highest baseline CMV IgG tertile had increasing annual rates of soluble CD14 and CRP levels, which was not observed for the low CMV IgG tertile group. Compared with pre-ART visits, CMV IgG antibody levels were higher post-ART initiation, and concurrent levels remained associated with soluble CD14 and CRP during suppressive ART (n = 88 person-visits).ConclusionThe magnitude of the immune response to CMV was associated with HIV disease progression and immune activation in sub-Saharan Africa.

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.

Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.

1 | INTRODUCTION Data suggesting a potential link between male circumcision and HIV infection at the individual and population levels were published in 1988 [1] and 1989 [2]. A meta-analysis [...], Introduction: WHO/UNAIDS recommended Voluntary Medical Male Circumcision in 2007 based on systematic review of observational studies prior to 1999 and three randomized controlled trials (RCTs). To inform updated WHO guidance, we conducted a systematic review and meta-analysis of impact of circumcision on the risk of HIV infection among heterosexual men. Methods: Studies in PubMed of HIV incidence and changes in prevalence in heterosexual men by circumcision status were identified. Pooled incidence rate ratios were computed using fixed- and random-effects meta-analysis and risk of bias was assessed using the ROBINS-I tool. Results and Discussion: In three RCTs, the pooled incidence ratio was 0.41 (95% CI 0.30 to 0.56), with risk difference 10 (8 to 12) fewer infections per 1000 person-years (py). Pooled incidence ratios were 0.34 (0.24 to 0.49) in two post-RCT follow-up studies, 0.29 (0.19 to 0.43) in men at high HIV risk (five cohorts), 0.48 (0.33 to 0.70) in four community-based cohorts before circumcision scale-up, and 0.56 (0.49 to 0.64) (7 [6 to 8] fewer per 1000 py) in six community-based cohorts during circumcision and antiretroviral treatment scale-up. Heterogeneity between studies was low except in men at high HIV risk. We estimated 520,000 (425,000 to 605,000) fewer infections occurred in men by end of 2018 from 22.7 million circumcisions performed since 2008 and increasing by 155,000 (125,000 to 180,000) annually if epidemic conditions remain similar. After exclusion of studies with high risk of bias and those conducted outside Africa, pooled incidence ratios were similar. There was no evidence of confounding nor changes in risk behaviour following circumcision. In post-hoc exploratory analyses we observed a trend of decreasing effectiveness of circumcision in cohorts with lower HIV incidence. Conclusions: Efficacy of medical male circumcision on HIV incidence from randomized controlled trials was supported by effectiveness from observational studies in populations with diverse HIV risk and changing epidemic contexts. Voluntary Medical Male Circumcision remains an important evidence-based intervention for control of generalized HIV epidemics. Keywords: circumcision male; HIV incidence; HIV prevention; meta-analysis; review

Intimate partner violence (IPV) has a bidirectional relationship with HIV infection. Researchers from the Rakai Health Sciences Program (RHSP), an HIV research and services organization in rural Uganda, conducted a combination IPV and HIV prevention intervention called the Safe Homes and Respect for Everyone (SHARE) Project between 2005 and 2009. SHARE was associated with significant declines in physical and sexual IPV and overall HIV incidence, and its model could be adopted as a promising practice in other settings. In this article we describe how SHARE's IPV-prevention strategies were integrated into RHSP's existing HIV programming and provide recommendations for replication of the approach.

Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.

Individuals who communicate their HIV diagnosis to sexual partners may be at increased risk of intimate partner violence (IPV). The authors examined past year self-reported IPV associated with communication of HIV diagnosis and other factors, in a sample of 679 sexually active; HIV-positive individuals age 18 to 49, who received HIV results and posttest counselling 12 months or more prior to the survey in Rakai, Uganda, using log-binomial multivariable regression. The rates of verbal and physical abuse among married individuals were significantly higher compared to unmarried persons, respectively. Physical abuse was significantly higher among women compared to men. IPV was not significantly associated with communication of HIV diagnosis. Interventions to prevent IPV among married HIV-positive individuals particularly women, at the community level, are needed.

BackgroundIntimate 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.MethodsWe 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.FindingsBetween 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).InterpretationSHARE 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.FundingBill & Melinda Gates Foundation, US National Institutes of Health, WHO, President's Emergency Plan for AIDS Relief, Fogarty International Center.