Estimation of cause-specific mortality in Rakai, Uganda, using verbal autopsy 1999-2019.

BACKGROUND: There are scant data on the causes of adult deaths in sub-Saharan Africa. We estimated the level and trends in adult mortality, overall and by different causes, in rural Rakai, Uganda, by age, sex, and HIV status. OBJECTIVES: To estimate and analyse adult cause-specific mortality trends in Rakai, Uganda. METHODOLOGY: Mortality information by cause, age, sex, and HIV status was recorded in the Rakai Community Cohort study using verbal autopsy interviews, HIV serosurveys, and residency data. We estimated the average number of years lived in adulthood. Using demographic decomposition methods, we estimated the contribution of each cause of death to adult mortality based on the average number of years lived in adulthood. RESULTS: Between 1999 and 2019, 63082 adults (15-60 years) were censused, with 1670 deaths registered. Of these, 1656 (99.2%) had completed cause of death data from verbal autopsy. The crude adult death rate was 5.60 (95% confidence interval (CI): 5.33-5.87) per 1000 person-years of observation (pyo). The crude death rate decreased from 11.41 (95% CI: 10.61-12.28) to 3.27 (95% CI: 2.89-3.68) per 1000 pyo between 1999-2004 and 2015-2019. The average number of years lived in adulthood increased in people living with HIV and decreased in HIV-negative individuals between 2000 and 2019. Communicable diseases, primarily HIV and Malaria, had the biggest decreases, which improved the average number of years lived by approximately extra 12 years of life in females and 6 years in males. There were increases in deaths due to non-communicable diseases and external causes, which reduced the average number of years lived in adulthood by 2.0 years and 1.5 years in females and males, respectively. CONCLUSION: There has been a significant decline in overall mortality from 1999 to 2019, with the greatest decline seen in people living with HIV since the availability of antiretroviral therapy in 2004. By 2020, the predominant causes of death among females were non-communicable diseases, with external causes of death dominating in males.

Main findings: There are significant declines in mortality in people living with HIV. However, mortality in HIV-negative people increased due to non-communicable diseases in females, and injuries and external causes of death among males.Added knowledge: In this HIV-endemic area, decreasing adult mortality has been documented over the last 20 years. This paper benchmarks the changes in cause-specific mortality in this area.Global health impact for policy action: As in many African countries, more effort is needed to reduce mortality for non-communicable diseases, injuries, and external causes of death as these seem to have been neglected.

Household transport ownership and HIV viral suppression in rural Uganda: a cross- sectional, population-based study.

Background Empirical data on transportation access and HIV treatment outcomes in sub-Saharan Africa are rare. We assessed the association between household transport ownership and HIV viral suppression in rural Uganda. Methods The study was conducted among people living with HIV aged 15-49 years using cross-sectional data from the Rakai Community Cohort Study (RCCS), collected from June 14, 2018, to November 6, 2020. Transport ownership was defined as household possession of a car, motorcycle, or bicycle. HIV viral suppression was defined as < 1000 HIV RNA copies/ml. Poisson regression with robust variance estimation identified unadjusted and adjusted prevalence ratios and 95% confidence intervals (CI) of HIV viral suppression by transport ownership. Results The study included 3,060 persons aged 15-49 living with HIV. Overall HIV viral suppression was 86.5% and was higher among women compared to men (89.3% versus 81.6%; adjusted prevalence ratio: 1.14, 95% CI: 1.10, 1.18). A total of 874 participants (28.6%) resided in households that owned at least one means of transport. HIV viral suppression was 79.8% among men and 88.2% among women from households without any means of transport, compared to 85.4% among men and 92.4% among women from households with at least one means of transport. Adjusted prevalence ratios of HIV viral suppression were 1.11 (95% CI: 1.04, 1.18) for males and 1.06 (95% CI: 1.03, 1.10) for females from households owning at least one means of transport compared with those from households with none. Conclusion There was increased HIV viral suppression among people living with HIV from households with transport means compared to those from households without transport means, suggesting transport may facilitate access to, and continued engagement with, HIV treatment services.

HIV epidemiologic trends among occupational groups in Rakai, Uganda: A population-based longitudinal study, 1999-2016.

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23-0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18-0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming.

Longitudinal patterns in indeterminate HIV rapid antibody test results: a population-based, prospective cohort study.

Rapid HIV tests are critical to HIV surveillance and universal testing and treatment programs. We assessed longitudinal patterns in indeterminate HIV rapid test results in an African population-based cohort. Prospective HIV rapid antibody test results, defined by two parallel rapid tests, among participants aged 15-49 years from three survey rounds of the Rakai Community Cohort Study, Uganda, from 2013 to 2018, were assessed. An indeterminate result was defined as any weak positive result or when one test was negative and the other was positive. A total of 31,405 participants contributed 54,459 person-visits, with 15,713 participants contributing multiple visits and 7,351 participants contributing 3 visits. The prevalence of indeterminate results was 2.7% (1,490/54,469). Of the participants with multiple visits who initially tested indeterminate (n = 591), 40.4% were negative, 18.6% were positive, and 41.0% were indeterminate at the subsequent visit. Of the participants with two consecutive indeterminate results who had a third visit (n = 67), 20.9% were negative, 9.0% were positive, and 70.2% remained indeterminate. Compared to a prior negative result, a prior indeterminate result was strongly associated with a subsequent indeterminate result [adjusted prevalence ratio, 23.0 (95% CI = 20.0-26.5)]. Compared to men, women were more likely to test indeterminate than negative [adjusted odds ratio, 2.3 (95% CI = 2.0-2.6)]. Indeterminate rapid HIV test results are highly correlated within an individual and 0.6% of the population persistently tested indeterminate over the study period. A substantial fraction of people with an indeterminate result subsequently tested HIV positive at the next visit, underscoring the importance of follow-up HIV testing protocols.IMPORTANCERapid HIV tests are a critical tool for expanding HIV testing and treatment to end the HIV epidemic. The interpretation and management of indeterminate rapid HIV test results pose a unique challenge for connecting all people living with HIV to the necessary care and treatment. Indeterminate rapid HIV test results are characterized by any weak positive result or discordant results (when one test is negative and the other is positive). We systematically tested all participants of a Ugandan population-based, longitudinal cohort study regardless of prior test results or HIV status to quantify longitudinal patterns in rapid HIV test results. We found that a substantial fraction (>15%) of participants with indeterminate rapid test results subsequently tested positive upon follow-up testing at the next visit. Our findings demonstrate the importance of follow-up HIV testing protocols for indeterminate rapid HIV test results.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Timing for maximum anaesthetic effect of topical cream during early infant circumcision (EIC) in Rakai, Uganda.

Objectives: The objective of this study is to determine the optimal timing for device-based infant circumcision under topical anaesthesia. Subjects/patients: We include infants aged 1-60 days who were enrolled in a field study of the no-flip ShangRing device at four hospitals in the Rakai region of south-central Uganda, between 5 February 2020 and 27 October 2020. Methods: Two hundred infants, aged 0-60 days, were enrolled, and EMLA cream was applied on the foreskin and entire penile shaft. The anaesthetic effect was assessed every 5 min by gentle application of artery forceps at the tip of the foreskin, starting at 10 min post-application until 60 min, the recommended time to start circumcision. The response was measured using the Neonatal Infant Pain Scale (NIPS). We determined the onset and duration of anaesthesia (defined as <20% of infants with NIPS score >4) and maximum anaesthesia (defined as <20% of infants with NIPS score >2). Results: Overall, NIPS scores decreased to a minimum and reversed before the recommended 60 min. Baseline response varied with age, with minimal response among infants aged 40 days. Overall, anaesthesia was achieved after at least 25 min and lasted 20-30 min. Maximum anaesthesia was achieved after at least 30 min (except among those aged >45 days where it was not achieved) and lasted up to 10 min. Conclusion: The optimal timing for maximum topical anaesthesia occurred before the recommended 60 min of waiting time. A shorter waiting time and speed may be efficient for mass device-based circumcision.

Mixed Methods, Implementation Science Evaluation of a Community Health Worker Strategy for HIV Service Engagement in Uganda.

BACKGROUND: A trial found that a community health worker (CHW) strategy using "Health Scouts" improved HIV care uptake and ART coverage. To better understand outcomes and areas for improvement, we conducted an implementation science evaluation. METHODS: Using the RE-AIM framework, quantitative methods included analyses of a community-wide survey (n = 1903), CHW log books, and phone application data. Qualitative methods included in-depth interviews (n = 72) with CHWs, clients, staff, and community leaders. RESULTS: Thirteen Health Scouts logged 11,221 counseling sessions; 2532 unique clients were counseled. 95.7% (1789 of 1891) of residents reported awareness of the Health Scouts. Overall, reach (self-reported receipt of counseling) was 30.7% (580 of 1891). Unreached residents were more likely to be male and HIV seronegative ( P < 0.05). Qualitative themes included the following: (1) reach was promoted by perceived usefulness but deterred by busy client lifestyles and stigma, (2) effectiveness was enabled through good acceptability and consistency with the conceptual framework, (3) adoption was facilitated by positive impacts on HIV service engagement, and (4) implementation fidelity was initially promoted by the CHW phone application but deterred by mobility. Maintenance showed consistent counseling sessions over time. The findings suggested the strategy was fundamentally sound but had suboptimal reach. Future iterations could consider adaptations to improve reach to priority populations, testing the need for mobile health support, and additional community sensitization to reduce stigma. CONCLUSIONS: A CHW strategy to promote HIV services was implemented with moderate success in an HIV hyperendemic setting and should be considered for adoption and scale-up in other communities as part of comprehensive HIV epidemic control efforts. TRIAL REGISTRATION: ClinicalTrials.gov Trial Number NCT02556957.

Dynamics of Pre-Exposure (PrEP) Eligibility Because of Waxing and Waning of HIV Risk in Rakai, Uganda.

BACKGROUND: We conducted a retrospective population-based study to describe longitudinal patterns of prevalence, incidence, discontinuation, resumption, and durability of substantial HIV risk behaviors (SHR) for pre-exposure prophylaxis (PrEP) eligibility. METHODS: The study was conducted among HIV-negative study participants aged 15-49 years who participated in survey rounds of the Rakai Community Cohort Study between August 2011 and June 2018. Substantial HIV risk was defined based on the Uganda national PrEP eligibility as reporting sexual intercourse with >1 partner of unknown HIV status, nonmarital sex without a condom, having genital ulcers, or having transactional sex. Resumption of SHR meant resuming of SHR after stopping SHR, whereas persistence of SHR meant SHR on >1 consecutive visit. We used generalized estimation equations with log-binomial regression models and robust variance to estimate survey-specific prevalence ratios; Generalized estimation equations with modified Poisson regression models and robust variance to estimate incidence ratios for incidence, discontinuation, and resumption of PrEP eligibility. FINDINGS: Incidence of PrEP eligibility increased from 11.4/100 person-years (pys) in the first intersurvey period to 13.9/100 pys (adjusted incidence rate ratios = 1.28; 95%CI = 1.10-1.30) and declined to 12.6/100 pys (adjusted incidence rate ratios = 1.06; 95%CI = 0.98-1.15) in the second and third intersurvey periods, respectively. Discontinuation rates of SHR for PrEP eligibility were stable (ranging 34.9/100 pys-37.3/100 pys; P = 0.207), whereas resumption reduced from 25.0/100 pys to 14.5/100 pys ( P < 0.001). PrEP eligibility episodes lasted a median time of 20 months (IQR = 10-51). INTERPRETATION: Pre-exposure prophylaxis use should be tailored to the dynamic nature of PrEP eligibility. Preventive-effective adherence should be adopted for assessment of attrition in PrEP programs.

Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted, while HIV transmission to girls and women (aged 15-24 years) from older men declined by about one third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programs to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Cardiovascular (Framingham) and type II diabetes (Finnish Diabetes) risk scores: a qualitative study of local knowledge of diet, physical activity and body measurements in rural Rakai, Uganda.

BACKGROUND: Non-communicable diseases such as cardiovascular conditions and diabetes are rising in sub-Saharan Africa. Prevention strategies to mitigate non-communicable diseases include improving diet, physical activity, early diagnosis, and long-term management. Early identification of individuals at risk based on risk-score models - such as the Framingham Risk Score (FRS) for 10-year risk of cardiovascular disease and the Finnish type 2 Diabetes risk score (FINDRISC) for type 2 diabetes which are used in high-income settings - have not been well assessed in sub-Saharan Africa. The purpose of this study was to qualitatively assess local knowledge of components of these risk scores in a rural Ugandan setting. METHODS: Semi-structured qualitative in-depth interviews were conducted with a purposively selected sample of 15 participants who had responded to the FRS and FINDRISC questionnaires and procedures embedded in the Rakai Community Cohort Study. Data were summarized and categorized using content analysis, with support of Atlas.ti. RESULTS: Participants described local terms for hypertension ("pulessa") and type 2 diabetes ("sukaali"). Most participants understood physical activity as leisure physical activity, but when probed would also include physical activity linked to routine farm work. Vegetables were typically described as "plants", "leafy greens", and "side dish". Vegetable and fruit consumption was described as varying seasonally, with peak availability in December after the rainy season. Participants perceived themselves to have good knowledge about their family members' history of type 2 diabetes and hypertension. CONCLUSIONS: While most items of the FRS and FINDRISC were generally well understood, physical activity needs further clarification. It is important to consider the seasonality of fruits and vegetables, especially in rural resource-poor settings. Current risk scores will need to be locally adapted to estimate the 10-year risk of cardiovascular diseases and type 2 diabetes in this setting.

Makerere's contribution to the development of a high impact HIV research population-based cohort in the Rakai Region, Uganda.

Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV prevention, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.

The HIV and sexually transmitted infection syndemic following mass scale-up of combination HIV interventions in two communities in southern Uganda: a population-based cross-sectional study.

BACKGROUND: 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. METHODS: 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). FINDINGS: 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. INTERPRETATION: 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. FUNDING: National Institutes of Health.

ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: a multicentre, non-inferiority, adaptive, randomised controlled trial.

BACKGROUND: Use of medical devices represents a unique opportunity to facilitate scale-up of early infant male circumcision (EIMC) across sub-Saharan Africa. The ShangRing, a circumcision device prequalified by WHO, is approved for use in adults and adolescents and requires topical anaesthesia only. We aimed to investigate the safety and efficacy of the ShangRing versus the Mogen clamp for EIMC in infants across eastern sub-Saharan Africa. METHODS: In this multicentre, non-inferiority, open-label, randomised controlled trial, we enrolled healthy male infants (aged <60 days), with a gestational age of at least 37 weeks and a birthweight of at least 2·5 kg, from 11 community and referral centres in Kenya, Tanzania, and Uganda. Infants were randomly assigned (1:1) by a computer-generated text message service to undergo EIMC by either the ShangRing or the Mogen clamp. The primary endpoint was safety, defined as the number and severity of adverse events (AEs), analysed in the intention-to-treat population (all infants who underwent an EIMC procedure) with a non-inferiority margin of 2% for the difference in moderate and severe AEs. This trial is registered with Clinical. TRIALS: gov, NCT03338699, and is complete. FINDINGS: Between Sept 17, 2018, and Dec 20, 2019, a total of 1420 infants were assessed for eligibility, of whom 1378 (97·0%) were enrolled. 689 (50·0%) infants were randomly assigned to undergo EIMC by ShangRing and 689 (50·0%) by Mogen clamp. 43 (6·2%) adverse events were observed in the ShangRing group and 61 (8·9%) in the Mogen clamp group (p=0·078). The most common treatment-related AE was intraoperative pain (Neonatal Infant Pain Scale score ≥5), with 19 (2·8%) events in the ShangRing and 23 (3·3%) in the Mogel clamp group. Rates of moderate and severe AEs were similar between both groups (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference -0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). No treatment-related deaths were reported. INTERPRETATION: Use of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa. FUNDING: Bill & Melinda Gates Foundation.

Smoker characteristics and trends in tobacco smoking in Rakai, Uganda, 2010-2018.

INTRODUCTION: Tobacco use is a major public health concern, particularly in low- and middle-income countries where 80% of the world's smokers reside. There is limited population-based data from rural Africa on patterns of tobacco smoking and smoker characteristics. We assessed trends in rates of smoking, characteristics of smokers, and factors associated with smoking using repeat population-based cross-sectional surveys in south-central Uganda. METHODS: Data accrued over five survey rounds (2010-2018) of the Rakai Community Cohort Study (RCCS) from consenting individuals aged 15-49 years including sociodemographic and behavioral characteristics and smoking status. Proportions of smokers per survey were compared using χ2 test for trends, and factors associated with smoking were assessed by multivariable logistic regression. RESULTS: The prevalence of tobacco smoking in the general population declined from 7.3% in 2010-2011 to 5.1% in 2016-2018, p<0.001. Smoking rates declined among males (13.9-9.2%) and females (2.2-1.8%) from 2010-2011 to 2016-2018. Smoking prevalence was higher among previously married (11.8-11.7%) compared to currently (8.4-5.3%) and never married persons (3.1-1.8%) from 2010-2011 to 2016-2018. Older age (≥35 years) was associated with higher odds of smoking (AOR=8.72; 95% CI: 5.68-13.39 in 2010-2011 and AOR=9.03; 95% CI: 5.42-15.06 in 2016-2018) compared to those aged <35 years (AOR=4.73; 95% CI: 3.15-7.12 in 2010-2011 and AOR=4.83; 95% CI: 2.95-7.91 in 2016-2018). Primary and secondary/higher education level was significantly associated with lower odds of smoking (AOR=0.20; 95% CI: 0.14-0.29 in 2010-2011 and AOR=0.26; 95% CI: 0.18-0.39 in 2016-2018) compared to no education (AOR=0.43; 95% CI: 0.31-0.59 in 2010-2011 and AOR=0.48; 95% CI: 0.34-0.68 in 2016-2018). Number of sexual partners and HIV status were not associated with smoking. CONCLUSIONS: We observed declining trends in tobacco smoking in the Rakai region of rural Uganda. Smoking was more prevalent in men, older individuals, individuals who were previously married, and individuals with lower education. The decline in smoking may be due to tobacco control efforts, but there is a continued need to target sub-populations with higher smoking prevalence.

High Rates of Pre-exposure Prophylaxis Eligibility and Associated HIV Incidence in a Population With a Generalized HIV Epidemic in Rakai, Uganda.

BACKGROUND: The utility of using pre-exposure prophylaxis (PrEP) eligibility assessments to identify eligibility in general populations has not been well studied in sub-Saharan Africa. We used the Rakai Community Cohort Study to conduct a cross-sectional analysis to estimate PrEP eligibility and a cohort analysis to estimate HIV incidence associated with PrEP eligibility. METHODS: Based on Uganda's national PrEP eligibility tool, we defined eligibility as reporting at least one of the following HIV risks in the past 12 months: sexual intercourse with more than one partner of unknown HIV status; nonmarital sex act without a condom; sex engagement in exchange for money, goods, or services; or experiencing genital ulcers. We used log-binomial and modified Poisson models to estimate prevalence ratios for PrEP eligibility and HIV incidence, respectively. FINDINGS: We identified 12,764 participants among whom to estimate PrEP eligibility prevalence and 11,363 participants with 17,381 follow-up visits and 30,721 person-years (pys) of observation to estimate HIV incidence. Overall, 29% met at least one of the eligibility criteria. HIV incidence was significantly higher in PrEP-eligible versus non-PrEP-eligible participants (0.91/100 pys versus 0.41/100 pys; P < 0.001) and independently higher in PrEP-eligible versus non-PrEP-eligible female participants (1.18/100 pys versus 0.50/100 pys; P < 0.001). Among uncircumcised male participants, HIV incidence was significantly higher in PrEP-eligible versus non-PrEP-eligible participants (1.07/100 pys versus 0.27/100 pys; P = 0.001), but there was no significant difference for circumcised male participants. INTERPRETATION: Implementing PrEP as a standard HIV prevention tool in generalized HIV epidemics beyond currently recognized high-risk key populations could further reduce HIV acquisition and aid epidemic control efforts.

Hypertension and Socioeconomic Status in South Central Uganda: A Population-Based Cohort Study.

Background: Limited studies exploring the impact of socioeconomic status (SES) on hypertension in Africa suggest a positive association between higher SES and hypertension. The economic development in sub-Saharan African countries has led to changes in SES and associated changes in lifestyle, diet, and physical activity, which may affect the relationship between hypertension and SES differently compared with higher income countries. This cross-sectional study from a large population-based cohort, the Rakai Community Cohort Study (RCCS), examines SES, hypertension prevalence, and associated risk factors in the rural Rakai Region in south-central Uganda. Methods: Adults aged 30-49 years residing in 41 RCCS fishing, trading, and agrarian communities, were surveyed with biometric data obtained between 2016 and 2018. The primary outcome was hypertension (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 80 mmHg). Modified Poisson regression assessed the adjusted prevalence ratios (PR) of hypertension associated with SES; body mass index (BMI) was explored as a potential mediator. Results: Among 9,654 adults, 20.8% had hypertension (males 21.2%; females 20.4 %). Participants with hypertension were older (39.0 ± 6.0 vs. 37.8 ± 5.0; p < 0.001). Higher SES was associated with overweight or obese BMI categories (p < 0.001). In the multivariable model, hypertension was associated with the highest SES category (aPR 1.23; confidence interval 1.09-1.38; p = 0.001), older age, male sex, alcohol use, and living in fishing communities and inversely associated with smoking and positive HIV serostatus. When BMI was included in the model, there was no association between SES and hypertension (aPR 1.02; CI 0.90-1.15, p = 0.76). Conclusion: Hypertension is common in rural Uganda among individuals with higher SES and appears to be mediated by BMI. Targeted interventions could focus on lifestyle modification among highest-risk groups to optimize public health impact. Key Messages: What is already known about this subject? Hypertension is an important modifiable risk factor for cardiovascular disease.There are few large epidemiological studies that investigate the relationship between hypertension and socioeconomic status in low-income countries. What are the new findings? Hypertension is common among adults in rural South-Central Uganda, particularly among those with higher socioeconomic status.BMI is a mediator of the relationship between hypertension and socioeconomic status. How might it impact on clinical practice in the foreseeable future? These findings suggest that public health interventions and community efforts to prevent chronic cardiovascular disease and hypertension should focus on lifestyle modification by elucidating obesity risk perception and health risk awareness, particularly among those of higher socioeconomic status.

HIV combination prevention and declining orphanhood among adolescents, Rakai, Uganda, 2001-18: an observational community cohort study.

BACKGROUND: Orphanhood increased markedly in the 1980s and 1990s in sub-Saharan Africa because of HIV-related mortality. Little is known about the contribution of HIV interventions, such as antiretroviral therapy (ART) and male medical circumcision, to more recent trends in orphanhood. In this study, we examined trends over time in maternal-only, paternal-only, and double orphanhood among adolescents before and after ART and male medical circumcision became widely available in the Rakai region of south-central Uganda. We sought to understand the association between adolescent orphanhood and HIV combination prevention (community-level ART use and prevalence of male medical circumcision). We hypothesised that increasing combination prevention, including greater use of ART and higher prevalence of male medical circumcision, would be associated with a lower probability of orphanhood. METHODS: We examined the prevalence of orphanhood among adolescents aged 15-19 years, before and after roll-out of ART in mid-2004 and male medical circumcision in 2007, using data from 28 continuously followed communities within the Rakai Community Cohort Study. We used multinomial logistic regression with clustered SEs to estimate adjusted relative risk ratios (RRs) for maternal-only, paternal-only, and double orphanhood compared with non-orphanhood over 11 survey rounds between 2001 and 2018. Controlling for community HIV prevalence, household socioeconomic status, and adolescent age, we examined the association between community prevalence of ART use among people living with HIV and prevalence of male circumcision, including traditional circumcision. The primary outcome was orphanhood among adolescents aged 15-19 years. FINDINGS: Orphanhood declined from 52% (920 of 1768 participants) in 2001-02 to 23% (592 of 2609 participants) by 2016-18 (p<0·0001), while double orphanhood declined from 20% (346 of 1768 participants) to 3% (86 of 2609 participants) (p<0·0001). Community prevalence of ART use among people living with HIV increased from 11% (105 of 945 participants) in 2005-06 to 78% (1163 of 1485 participants) in 2016-18. Male circumcision rates rose from 19% (147 of 790 participants) in 2005-06 to 65% (3535 of 5433 participants) in 2016-18. In the multinomial logistic regression model, a 10% increase in community prevalence of ART use was associated with a decrease in maternal orphanhood (adjusted relative RR 0·90, 95% CI 0·85-0·95) and double orphanhood (0·80, 0·75-0·85). In the post-ART era, a 10% increase in the community prevalence of male circumcision was associated with a decrease in paternal orphanhood (2005-18, adjusted relative RR 0·92, 0·87-0·97) and double orphanhood (0·91, 0·85-0·98). INTERPRETATION: Widespread availability and uptake of HIV combination prevention was associated with marked reductions in orphanhood among adolescents. Reductions in orphanhood promise improved health and social outcomes for young people. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases.

Overweight and obesity in south central Uganda: A population-based study.

Obesity is a rapidly growing global health challenge, but there are few population-level studies from non-urban settings in sub-Saharan Africa. We evaluated the prevalence of overweight (body mass index (BMI)>25 kg/m2), obesity (BMI>30 kg/m2), and associated factors using data from May 2018 to November 2020 from the Rakai Community Cohort Study, a population-based cohort of residents aged 15 to 49 living in forty-one fishing, trading, and agrarian communities in South Central Uganda. Modified Poisson regression was used to estimate adjusted prevalence risk ratios (PRR) and 95% confidence intervals (CI) in 18,079 participants. The overall mean BMI was 22.9 kg/m2. Mean BMI was 21.5 kg/m2 and 24.1 kg/m2 for males and females, respectively. The prevalence of overweight and obesity were 22.8% and 6.2%, respectively. Females had a higher probability of overweight/obesity (PRR: 4.11, CI: 2.98-5.68) than males. For female participants, increasing age, higher socioeconomic status, residing in a trading or fishing community (PRR: 1.25, CI 1.16-1.35 and PRR: 1.17, CI 1.10-1.25, respectively), being currently or previously married (PRR: 1.22, CI 1.07-1.40 and PRR: 1.16, CI 1.01-1.34, respectively), working in a bar/restaurant (PRR: 1.29, CI 1.17-1.45), trading/shopkeeping (PRR: 1.38, CI 1.29-1.48), and reporting alcohol use in the last year (PRR: 1.21, CI 1.10-1.33) were risk factors for overweight/obese. For male participants, increasing age, higher socioeconomic status, being currently married (PRR: 1.94, CI 1.50-2.50), residing in a fishing community (PRR: 1.68, CI 1.40-2.02), working in a bar/restaurant (PRR: 2.20, CI 1.10-4.40), trading/shopkeeping (PRR: 1.75, CI 1.45-2.11), or fishing (PRR: 1.32, CI 1.03-1.69) increased the probability of overweight/obesity. Non-Muslim participants, male smokers, and HIV-positive females had a lower probability of overweight/obese. The prevalence of overweight/obesity in non-urban Ugandans is substantial. Targeted interventions to high-risk subgroups in this population are needed.

Prevalence of Untreated HIV and Associated Risk Behaviors Among the Sexual Partners of Recent Migrants and Long-term Residents in Rakai, Uganda.

BACKGROUND: Migrants in sub-Saharan Africa are at increased risk of HIV acquisition after migration, but little is known about their sexual partners at place of destination. SETTING: Rakai Community Cohort Study (RCCS) in Uganda. METHODS: From 1999 to 2016, persons aged 15-49 years were surveyed in the RCCS and reported on their 4 most recent sexual partners in the last year. We compared the characteristics of sexual partners reported by migrants moving into RCCS communities in the last 2 years (ie, in-migrants) with those of long-term residents with no recent migration history. Among a subset of participants in cohabitating epidemiologically linked couples of known HIV serostatus, we also assessed prevalence of having ≥1 untreated HIV-positive partner among in-migrants and long-term residents. RESULTS: One hundred sixteen thousand seven hundred forty-four sexual partners were reported by 29,423 participants. The sexual partnerships of in-migrants were significantly less likely to be marital, more likely to span community boundaries, and shorter in duration than those of long-term residents. In-migrants also reported more sexual partners and were less likely to know their partner's HIV status or to have told their partner their HIV status. Among 7558 epidemiologically linked couples, HIV-negative in-migrants were more likely to partner with untreated HIV-positive persons compared with HIV-negative long-term residents (women: 6.3% vs. 4.1%; prevalence risk ratio = 1.77, 95% confidence interval: 1.49 to 2.11; men: 6.9% vs. 3.9%; prevalence risk ratio = 1.72, 95% confidence interval: 1.38-2.14). CONCLUSION: There is a higher frequency of risky sexual behaviors among the partnerships of in-migrants compared with those of long-term residents. Among cohabitating couples, in-migrants are more likely to partner with untreated HIV-positive individuals.

Improvement in depressive symptoms after antiretroviral therapy initiation in people with HIV in Rakai, Uganda.

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies-Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P's < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aß-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences.