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BackgroundAlcohol use is common among persons living with HIV (PWH) in Uganda and associated with poor HIV care outcomes; findings regarding the relationship between alcohol use and viral suppression (VS) have been inconclusive.MethodsData from two rounds (2017-2020) of the Rakai Community Cohort Study, an open population-based cohort study in the Rakai region, Uganda, were analyzed. Two alcohol exposures were explored: past year alcohol use and alcohol-related consequences. Multivariable models (GEE) were used to estimate associations between alcohol exposures and VS for the overall sample and stratified by sex, adjusting for repeated measurement. Causal mediation by ART use was explored.ResultsOver half (55 %) of participants (n = 3823 PWH) reported alcohol use at baseline; 37.8 % of those reporting alcohol use reported alcohol-related consequences. ART use and VS at baseline significantly differed by alcohol use with person reporting alcohol use being less likely to be on ART or VS. Alcohol use was significantly associated with decreased odds of VS among women but not men (adj. OR 0.72 95 % CI 0.58-0.89, p = 0.0031). However, among males who use alcohol, experiencing alcohol-related consequences was significantly associated with decreased odds of VS (adj. OR 0.69 95 % CI 0.54-0.88, p = 0.0034). The relationships between both alcohol exposures and VS were not significant in models restricted to persons on ART.ConclusionsWe provide sex-stratified estimates of associations between two alcohol measures and VS in the context of current HIV treatment guidelines. This study confirms that alcohol use is adversely associated with VS but ART use mediates this pathway, suggesting that initiation and retention on ART are critical steps to addressing alcohol-related disparities in VS.

: Introduction: Population‐level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale‐up. Methods: In 2015–2020, we measured VLS ( Results: Overall, 3080 participants contributed 4604 visit‐pairs over three survey rounds. Most visit‐pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow‐up, 91.3% of which was high‐level viraemia. One‐fifth (20.8%) of visit‐pairs exhibiting persistent high‐level viraemia self‐reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high‐level viraemia varied substantially across communities and was significantly elevated among young persons aged 15–29 years (vs. 40‐ to 49‐year‐olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21–3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87–3.07), persons reporting inconsistent condom use with non‐marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10–1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03–1.16). The prevalence of persistent high‐level viraemia was highest among males Conclusions: Following universal ART provision, most persons living with HIV in south‐central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high‐level viraemia for ≥12 months and reported higher‐risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control., INTRODUCTION Universal Test and Treat (UTT) signalled a global paradigm shift in HIV control efforts through expanded antiretroviral therapy (ART) eligibility. Randomized trials in sub‐Saharan Africa demonstrated population‐level benefits of [...]

: Introduction: Antiretroviral treatment (ART) sharing has been reported among fishermen and sex workers in Uganda and South Africa. However, no population‐based studies have documented ART diversion prevalence (including sharing [giving/receiving], buying and selling) or its relationship with viremia among men and women living with HIV in Africa. Methods: In 2018–2020, we surveyed people living with HIV aged 15–49 years in 41 communities in the Rakai Community Cohort Study, a population‐based cohort in south‐central Uganda. We assessed the prevalence and correlates of self‐reported lifetime and past‐year ART diversion, stratifying by age and gender and documenting sources of diverted drugs. We used log‐binomial regression to quantify the relationship between diversion patterns and viremia (viral load >40 copies/ml), reported as unadjusted and adjusted prevalence ratios (aPR) with 95% confidence intervals (CI). Results: Of 2852 people living with HIV and self‐reporting current ART use, 266 (9.3%) reported lifetime ART diversion. Giving/receiving drugs were most common; few participants reported buying, and none reported selling. Men (12.9%) were more likely to report lifetime diversion than women (7.4%), with men aged 25–34 reporting high levels of sharing (18.9%). Friends were the most common sources of shared drugs, followed by spouses/sexual partners. Patterns of lifetime and past‐year diversion were similar. Among participants with viral load results, 8.6% were viraemic. In adjusted analyses, people who reported only giving ART were nearly twice as likely to be viraemic than those who reported no diversion (aPR: 1.94, 95% CI: 1.10−3.44), and those reporting only receiving ART were less likely to exhibit viremia (aPR: 0.46, 95% CI: 0.12−1.79), although the latter was not statistically significant. Reporting both giving and receiving ART was not associated with viremia (aPR: 0.79, 95% CI: 0.43−1.46). Reporting buying ART, though rare, was also correlated with higher rates of viremia, but this relationship was not statistically significant (aPR: 1.98, 95% CI: 0.72−5.45). Conclusions: ART sharing is common among persons reporting ART use in rural Uganda, particularly among men. Sharing ART was associated with viremia, and receiving ART may facilitate viral suppression. HIV programmes may benefit from considering ART sharing in counselling messages., INTRODUCTION Drug diversion is broadly conceptualized as the transfer of prescribed medication from the individual to whom it was prescribed to a different individual [1]. Drug diversion may include sharing [...]

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.

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]

Background The impact of migration on HIV risk among non-migrating household members is poorly understood. We measured HIV incidence among non-migrants living in households with and without migrants in Uganda. Methods We used four survey rounds of data collected from July 2011 to May 2018 from non-migrant participants aged 15–49 years in the Rakai Community Cohort Study. Non-migrants were individuals with no-migration between surveys or at the prior survey. Household migration was defined as ≥1 household member migrating into or out of the house from another community between surveys (∼18 months). Incident HIV was defined as testing HIV seropositive following a negative result. Incidence rate ratios (IRRs) were estimated using Poisson regression with generalized estimating equations. Analyses were stratified by gender, migration into or out of the household and the relationship between non-migrants and migrants (e.g. spouse, child). Results About 11 318 non-migrants (5674 women) were followed for 37 320 person-years. Twenty-eight percent (6059/21 370) of non-migrant person-visits had recent migration into or out of the household, and 240 HIV incident cases were identified. Overall, non-migrants in migrant households were not at greater risk of acquiring HIV than non-migrants in households without any migration. However, men were significantly more likely to acquire HIV if their spouse had recently migrated in [adjusted IRR: 2.12; 95% confidence interval (CI): 1.05–4.27] or out (adjusted IRR: 4.01; 95% CI, 2.16–7.44) compared with men with no spousal migration. Conclusions HIV incidence is higher among non-migrant men with migrant spouses. Targeted HIV testing and prevention interventions like pre-exposure prophylaxis could be considered for men with migrant spouses. [ABSTRACT FROM AUTHOR]

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.

Introduction: Pre-exposure prophylaxis (PrEP) programmes have been initiated in sub-Saharan Africa to prevent HIV acquisition in key populations at increased risk. However, data on PrEP uptake and retention in high-risk African communities are limited. We evaluated PrEP uptake and retention in HIV hyperendemic fishing villages and trading centres in south-centra Uganda between April 2018 and March 2019. Methods: PrEP eligibility was assessed using a national risk screening tool. Programme data were used to evaluate uptake and retention over 12 months. Multivariable modified Poisson regression estimated adjusted prevalence ratios (aPR) and 95% Confidence intervals (CIs) of uptake associated with covariates. We used Kaplan-Meier analysis to estimate retention and multivariable Cox regression to estimate adjusted relative hazards (aRH) and 95% CIs of discontinuation associated with covariates. Results and discussion: Of the 2985 HIV-negative individuals screened; 2750 (92.1%) were eligible; of whom 2,536 (92.2%) accepted PrEP. Male (aPR = 0.91, 95% CI = 0.85 to 0.97) and female (aPR = 0.85, 95% CI = 0.77 to 0.94) fisher folk were ess likely to accept compared to HIV-discordant couples. Median retention was 45.4 days for both men and women, whereas retention was higher among women (log rank, p < 0.001) overall. PrEP discontinuation was higher among female sex workers (aRH = 1.42, 95% CI = 1.09 to 1.83) and female fisher folk (aRH = 1.99, 95% CI = 1.46 to 2.72), compared to women in discordant couples. Male fisher folk (aRH = 1.37, 95% CI = 1.07 to 1.76) and male truck drivers (aRH = 1.49, 95% CI = 1.14 to 1.94) were more likely to discontinue compared to men in discordant couples. Women 30 to 34 years tended to have lower discontinuation rates compared to adolescents 15 to 19 years (RH = 0.78 [95% CI = 0.63 to 0.96]). Conclusions: PrEP uptake was high, but retention was very low especially among those at the highest risk of HIV: fisher folk, sex workers and truck drivers and adolescent girls. Research on reasons for PrEP discontinuation could help optimize retention. Keywords: PrEP; retention; HIV prevention; sex workers; risk factors; LMIC, 1 | INTRODUCTION Pre-exposure prophylaxis (PrEP) can help prevent HIV among individuals with substantial risk [1-3]. Studies of populations with high HIV risk in sub-Saharan Africa (SSA) including sex workers, [...]

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.

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level < 500/μl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/μl was 529/μl [95% confidence interval (CI): 517-541] in North America, 494/μl (95% CI: 429-559) in West Africa, 515/μl (95% CI: 508-522) in Southern Africa, 503/μl (95% CI: 478-528) in Asia and 437/μl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

ObjectiveRoutine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.DesignA cohort.MethodsWe examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27-33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance.ConclusionAmong HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.

ObjectiveTo delineate the association between baseline socioeconomic status (SES) indicators and mortality and lost to follow-up (LTFU) in a cohort of HIV-infected individuals enrolled in antiretroviral therapy (ART) in urban Uganda.DesignRetrospective cohort study nested in an antiretroviral clinic-based cohort.MethodsSES indicators including education, employment status, and a standardized wealth index, and other demographic and clinical variables were assessed at baseline among ART-treated patients in a clinic-based cohort in Kampala, Uganda. Confirmed mortality (primary outcome) and LTFU (secondary outcome) were actively ascertained over a 4-year follow-up period from 2005 to 2009.ResultsAmong 1763 adults [70.5% female; mean age, 36.2 years (SD = 8.4)] enrolled in ART, 14.4% (n = 253) were confirmed dead and 19.7% (n = 346) were LTFU at 4-year follow-up. No formal education [adjusted odds ratio (AOR) 1.76; 95% confidence interval (CI): 1.19 to 2.59], having fewer than 6 dependents (AOR 1.39; 95% CI: 1.04 to 1.86), unemployment (AOR 1.98; 95% CI: 1.48 to 2.66), and housing tenure index score (a component of the wealth index) (AOR 1.11; 95% CI: 1.00 to 1.23) were significantly associated with confirmed mortality at 4 years. SES indicators were not associated with LTFU at 4 years.ConclusionsBaseline SES indicators, including education, number of dependents, employment status, and components of a standard wealth index may indicate long-term vulnerability to mortality in patients with HIV/AIDS, despite uniform access to ART. Future studies delineating the pathways through which poverty and limited assets affect clinical outcomes may lead to more effective HIV interventions in low-resource settings.

Background A substantial proportion of persons on antiretroviral therapy (ART) considered lost to follow-up have actually transferred their human immunodeficiency virus (HIV) care to other facilities. However, the relationship between facility switching and virologic outcomes, including viral rebound, is poorly understood. Methods We used data from 40 communities (2015–2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. Persons aged 15–49 years with serologically confirmed HIV who self-reported ART use and contributed ≥1 follow-up visit were included. Facility switching and virologic outcomes were assessed between 2 consecutive study visits (ie, index and follow-up visits, interval of approximately 18 months). Those who reported different HIV treatment facilities between index and follow-up study visits were classified as having switched facilities. Virologic outcomes included viral rebound among individuals initially suppressed (<200 copies/mL). Multivariable Poisson regression was used to estimate associations between facility switching and viral rebound. Results Overall, 2257 persons who self-reported ART use (median age, 35 years; 65% female, 92% initially suppressed) contributed 3335 visit-pairs and 5959 person-years to the analysis. Facility switching was common (4.8 per 100 person-years; 95% confidence interval [CI], 4.2–5.5) and most pronounced in persons aged <30 years and fishing community residents. Among persons suppressed at their index visit (n = 2076), incidence of viral rebound was more than twice as high in persons who switched facilities (adjusted incidence rate ratio = 2.27; 95% CI, 1.16–4.45). Conclusions Facility switching was common and associated with viral rebound among persons initially suppressed. Investments in more agile, person-centered models for mobile clients are needed to address system inefficiencies and bottlenecks that can disrupt HIV care continuity. [ABSTRACT FROM AUTHOR]

Summary: Background: Despite numerous risk factors and serious consequences, little is known about metabolic dysfunction‐associated steatotic liver disease (MASLD) at population level in Africa. Aim: The aim of the study was to estimate the prevalence and risk factors of MASLD in people living with and without HIV in Uganda. Methods: We collected data from 37 communities in South Central Uganda between May 2016 and May 2018. We estimated MASLD prevalence using the fatty liver index and advanced liver fibrosis using the dynamic aspartate‐to‐alanine aminotransferase ratio. We collected additional data on sociodemographics, HIV and cardiovascular disease (CVD) risk factors. We used multivariable logistic regression to determine the association between HIV, CVD risk factors and MASLD. Results: We included 759 people with HIV and 704 HIV‐negative participants aged 35–49. MASLD prevalence was 14% in women and 8% in men; advanced liver fibrosis prevalence was estimated to be <1%. MASLD prevalence was more common in women (15% vs. 13%) and men (9% vs. 6%) with HIV. Being female (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.4–3.3) was associated with a higher odds of MASLD after adjustment for confounders; HIV infection was borderline associated with MASLD (OR = 1.4; 95% CI: 1.0–2.0). Conclusions: In a relatively young cohort in Uganda, 14% of women and 8% of men had MASLD. There was an indication of an association between HIV and MASLD in multivariable analysis. These data are the first to describe the population‐level burden of MASLD in sub‐Saharan Africa using data from a population‐based cohort. [ABSTRACT FROM AUTHOR]