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Abstract Background HIV treatment programs in Africa have implemented centralized testing for routine viral load monitoring (VLM), which may result in specimen processing delays inhibiting timely return of viral load results. Decentralized, point-of-care (PoC) VLM is a promising tool for expediting HIV clinical decision-making but remains unavailable in most African settings. We qualitatively explored the perceived feasibility and appropriateness of PoC VLM to address gaps along the viral load monitoring continuum in rural Uganda. Methods Between May and September 2022, we conducted 15 in-depth interviews with HIV clinicians (facility in-charges, clinical officers, nurses, counselors) and six focus group discussions with 47 peer health workers from three south-central Ugandan districts. Topics explored centralized VLM implementation and opportunities/challenges to optimizing routine VLM implementation with PoC testing platforms. We explored perspectives on PoC VLM suitability and feasibility using iterative thematic analysis. Applying the Framework Method, we then mapped salient constraints and enablers of PoC VLM to constructs from the Consolidated Framework for Implementation Research. Results Clinicians and peers alike emphasized centralized viral load monitoring’s resource-intensiveness and susceptibility to procedural/infrastructural bottlenecks (e.g., supply stockouts, testing backlogs, community tracing of clients with delayed VLM results), inhibiting timely clinical decision-making. Participants reacted enthusiastically to the prospect of PoC VLM, anticipating accelerated turnarounds in specimen processing, shorter and/or fewer client encounters with treatment services, and streamlined efficiencies in HIV care provision (including expedited VLM-driven clinical decision-making). Anticipated constraints to PoC VLM implementation included human resource requirements for processing large quantities of specimens (especially when machinery require repair), procurement and maintenance costs, training needs in the existing health workforce for operating point-of-care technology, and insufficient space in lower-tier health facilities to accommodate installation of new laboratory equipment. Conclusions Anticipated implementation challenges, primarily clustering around resource requirements, did not diminish enthusiasm for PoC VLM monitoring among rural Ugandan clinicians and peer health workers, who perceived PoC platforms as potential solutions to existing inefficiencies within the centralized VLM ecosystem. Prioritizing PoC VLM rollout in facilities with available resources for optimal implementation (e.g., adequate physical and fiscal infrastructure, capacity to manage high specimen volumes) could help overcome anticipated barriers to decentralizing viral load monitoring.

Abstract Background Vaccination has been recommended as one of the approaches for the control of COVID-19 pandemic. However, adequate vaccine coverage is critical to the effectiveness of the vaccine at population level. Data on acceptability of the vaccine in Ugandan urban areas are limited. This study examined the prevalence, factors associated with willingness to accept COVID-19 vaccine including reasons for not taking COVID-19 vaccine in a predominantly urban population of Wakiso, central Uganda. Methods Data were obtained from a cross-sectional study conducted between March 1st, 2021 and September 30th, 2021 in the urban population-based cohort of the Africa Medical and behavioral Sciences Organization (AMBSO). A Multivariable modified Poisson regression analysis was used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals of willingness to accept the COVID-19 vaccine. Results A total of 1,903 participants were enrolled in this study; 61% of whom were females. About 63% of participants indicated their willingness to accept the COVID-19 vaccine. Persons aged 13–19 years (aPR = 0.79; [95% CI: 0.74, 0.84]) or 20-29years (aPR = 0.93; [95% CI: 0.88, 0.98]) were less likely to accept the vaccine compared to persons aged 40–49 years. Persons with post-primary level of education (aPR = 1.05; [95% CI: 1.02, 1.09]) were more likely to accept the vaccine compared to persons with primary level of education. Additionally, students or individuals working in government (aPR = 1.13; [95% CI: 1.04, 1.23]) were more likely to accept the vaccine compared to individuals doing construction and Mechanic work as their main occupation. Reported reasons for not taking a COVID-19 vaccine included; concerns about side effects of the vaccine 154(57.0%), 64(23.7%) did not think the vaccines were effective, while 32(11.9%) did not like the vaccines. Conclusion A substantial proportion of individuals were not willing to accept the COVID-19 vaccine. Health education campaigns on vaccination within urban communities could help reduce COVID-19 vaccine misconceptions in the urban populations more especially the young and persons with low levels of formal education.

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.

Summary: Background: This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). Methods: We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. Findings: Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: −15.0%, (SD = 19.1); Mogen clamp Prevotella: −3.6% (11.2); ShangRing Veillonella: −11.3% (17.2); Mogen clamp Veillonella: −2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. Interpretation: Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. Funding: Bill and Melinda Gates Foundation.

Abstract Background Efforts have been invested towards cessation of tobacco use among youths aged 18–35 years, however, motivators for continued tobacco smoking and reasons for quitting are limited in Ugandan settings. Therefore, this study aimed to explore motivations for continued tobacco smoking and reasons for quitting in Wakiso district Uganda. Methods This study used explanatory sequential method. Data from a Population-based survey collected from October 2019 to September 2020 was used to select participants for this qualitative study. Twenty-three in-depths interviews were conducted from July to October 2021 among youths (18-35years old) who reported continued tobacco use and those who quit. Data were analyzed using a team-based thematic content approach with the help of NVivo. Results Data was collected from a total of twenty three participants, fourteen were tobacco quitters and nine were current tobacco smokers. Recurrent habit, desire to complement the use of other drugs, peer pressure, using smoking as a replacement for alcohol consumption, low tobacco prices, smoking as a tradition were reported as motivators for continued tobacco smoking. However, reported reasons for quitting smoking by youths included; packaging health warnings, school based prevention programs, fear of associated health risks due to tobacco use, embarrassment from family members. Conclusion Targeted, and tailored tobacco prevention counselling through family support programs, intensified health education on the risks of smoking, and implementing stronger health warnings on tobacco packaging can be employed to reduce or stop tobacco use among urban youth.

Background: In March 2020, Uganda enforced country-wide restrictions to control the spread of SARS-CoV-2, categorizing some health services, including family planning (FP), as non-essential. Globally, similar COVID-19 restrictions have been associated with increased vulnerability to reproductive coercion (RC) among women, due to changes in FP service availability and restricted access by partners. This study aims to investigate these dynamics in Uganda, specifically examining the impact of the COVID-19 lockdown on women's access to FP, their experiences of RC, and the relationship between RC and intimate partner violence (IPV). Methods: We conducted a cross-sectional analysis of data from 960 women participating in the AMBSO Population Health Surveillance Study (APHS) between August 2020 and March 2021 across Wakiso (N = 164) and Hoima (N = 796) districts in Uganda. Our analysis focused on women who were sexually active in the past month, using bivariate analyses to explore the associations between RC and recent experiences of sexual, physical, and verbal IPV. Findings: The most commonly reported FP methods were injectables (36.8 %) and implants (16 %). Despite the COVID-19 lockdown, less than one percent of participants reported an inability to access their preferred FP method. Notably, 3 % of the women experienced RC in the past 12 months. There was a significant association between RC and sexual IPV (p

Abstract 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 4) and maximum anaesthesia (defined as 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.

Abstract 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 (

ABSTRACT 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.

BackgroundGlobally, the prevalence of chronic non-communicable diseases (C-NCDs) and occurrence of multi-morbidity specifically, has been increasing and will continue to rise as life expectancy increases. The burden of mental health disorders has also been rising globally. In sub-Saharan Africa (SSA), literature on these health issues, which are interrelated, is scarce. This study assesses the prevalence of C-NCDs, and depressive and anxiety symptomology and examines the relationship between these issues among a sample of older adults in Uganda.MethodsBetween 2021-2022, 604 consenting adults aged 35 years and older were surveyed on a broad range of health issues for the ongoing AMBSO Population Health Surveillance (APHS) cohort study in Wakiso district. Descriptive analyses were performed to characterize the burden of C-NCDs (e.g. diabetes, hypertension), depression (PHQ-9 using a cutoff of ResultsMajority of participants were females (63.6%), median age was 46 (IQR: 39-54). Any C-NCDs prevalence was 18.7%, while 18.9% and 11.4%, had screening scores indicative of depressive and anxiety symptomology, respectively. Three percent (3.2%) had PHQ-9 scores indicative of moderate to severe depressive symptomology. In models adjusted for sociodemographic characteristics, there was 12% increased odds of suffering from C-NCDs for every unit increase in PHQ-9 score (AOR = 1.12, 95% CI: 1.10-1.20). Participants with any anxiety symptoms had 2.1 greater odds of suffering from C-NCD compared to those who did not have anxiety symptoms (AOR = 2.10, 95% CI: 1.21-3.70).ConclusionC-NCDs were prevalent in older adults, particularly among those experiencing mental health symptoms. Screening for C-NCDs and mental health disorders should be integrated into routine health care for older adults in the country. Early screening and identification of these health issues through primary health care could significantly reduce the public health burden attributable to mental health disorders and the incidence of multi-morbidity in Uganda.

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.

Introduction Self-collected samples (SCS) for sexually transmitted infection (STI) testing have been shown to be feasible and acceptable in high-resource settings. However, few studies have assessed the acceptability of SCS for STI testing in a general population in low-resource settings. This study explored the acceptability of SCS among adults in south-central Uganda.Methods Nested within the Rakai Community Cohort Study, we conducted semistructured interviews with 36 adults who SCS for STI testing. We analysed the data using an adapted version of the Framework Method.Results Overall, SCS was acceptable to both male and female participants, regardless of whether they reported recent STI symptoms. Perceived advantages of SCS over provider-collection included increased privacy and confidentiality, gentleness and efficiency. Disadvantages included the lack of provider involvement, fear of self-harm and the perception that SCS was unhygienic. Most participants preferred provider-collected samples to SCS. Nevertheless, almost all said they would recommend SCS and would do it again in the future.Conclusion SCS are acceptable among adults in this low-resource setting and could be offered as an additional option to expand STI diagnostic services.

Abstract 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.

The COVID-19 pandemic spread between neighboring countries through land, water, and air travel. Since May 2020, ministries of health for the Democratic Republic of the Congo, Tanzania, and Uganda have sought to clarify population movement patterns to improve their disease surveillance and pandemic response efforts. Ministry of Health–led teams completed focus group discussions with participatory mapping using country-adapted Population Connectivity Across Borders toolkits. They analyzed the qualitative and spatial data to prioritize locations for enhanced COVID-19 surveillance, community outreach, and cross-border collaboration. Each country employed varying toolkit strategies, but all countries applied the results to adapt their national and binational communicable disease response strategies during the pandemic, although the Democratic Republic of the Congo used only the raw data rather than generating datasets and digitized products. This 3-country comparison highlights how governments create preparedness and response strategies adapted to their unique sociocultural and cross-border dynamics to strengthen global health security.

Abstract 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.

Objective Since rapid population growth challenges longitudinal population-based HIV cohorts in Africa to maintain coverage of their target populations, this study evaluated whether the exclusion of some residents due to growing population size biases key HIV metrics like prevalence and population-level viremia.Design, setting and participants Data were obtained from the Rakai Community Cohort Study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. The study includes adults aged 15–49 years who were censused from 2019 to 2020.Measures We fit ensemble machine learning models to RCCS census and survey data to predict HIV seroprevalence and viremia (prevalence of those with viral load >1000 copies/mL) in the excluded population and evaluated whether their inclusion would change overall estimates.Results Of the 24 729 census-eligible residents, 2920 (12%) residents were excluded from the RCCS because they were living in new households. The predicted seroprevalence for these excluded residents was 10.8% (95% CI: 9.6% to 11.8%)—somewhat lower than 11.7% (95% CI: 11.2% to 12.3%) in the observed sample. Predicted seroprevalence for younger excluded residents aged 15–24 years was 4.9% (95% CI: 3.6% to 6.1%)—significantly higher than that in the observed sample for the same age group (2.6% (95% CI: 2.2% to 3.1%)), while predicted seroprevalence for older excluded residents aged 25–49 years was 15.0% (95% CI: 13.3% to 16.4%)—significantly lower than their counterparts in the observed sample (17.2% (95% CI: 16.4% to 18.1%)). Over all ages, the predicted prevalence of viremia in excluded residents (3.7% (95% CI: 3.0% to 4.5%)) was significantly higher than that in the observed sample (1.7% (95% CI: 1.5% to 1.9%)), resulting in a higher overall population-level viremia estimate of 2.1% (95% CI: 1.8% to 2.4%).Conclusions Exclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall, HIV seroprevalence estimates were not significantly affected.

Abstract Background Globally, key subpopulations such as healthcare workers (HCW) may have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to Personal Protective Equipment and lack of clarity on the extent/pattern of community spread may exacerbate this situation. The country established infection prevention/control measures such as lockdowns and proper hand hygiene. However, due to resource limitations and fatigue, compliance is low, posing continued onward transmission risk. This study aimed to describe extent of SARS-CoV-2 seroprevalence in selected populations within the Rakai region of Uganda. Methods From 30th November 2020 to 8th January 2021, we collected venous blood from 753 HCW at twenty-six health facilities in South-Central Uganda and from 227 population-cohort participants who reported specific COVID-19 like symptoms (fever, cough, loss of taste and appetite) in a prior phone-based survey conducted (between May and August 2020) during the first national lockdown. 636 plasma specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda were also retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek™ rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Overall seroprevalence in each participant group was estimated, adjusting for test performance. Results The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% [95%CI: 23.5, 29.8] with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the phone-based survey participants, 15.6% [95%CI: 10.9, 20.3] had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% [95%CI: 1.2, 3.5] were reactive. Conclusions Findings suggest high seroprevalence of antibodies to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether seroprevalence among plasma specimens collected prior to confirmation of the first COVID-19 case implies prior SARS-CoV-2 exposure in Uganda.

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 χ 2 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

Abstract Background Coronal sulcus (CS) anaerobe abundance and IL-8 levels are linked to HIV acquisition, and are dramatically reduced after penile circumcision (PC). The distal urethra may be the site of some HIV acquisition before PC, and presumably most acquisition post PC. We describe the immune milieu and microbiome of the distal urethra in uncircumcised Ugandan men, and define the impact of PC. Participants consisted of HIV-negative, genital symptom-free adult Ugandan men undergoing PC (n = 51). Urethral and coronal sulcus swabs were collected at baseline and at 6- and 12-months post-PC. Soluble immune factors were quantified by multiplex ELISA, and bacterial abundance assessed by 16S rRNA qPCR and sequencing. Results At baseline, the urethra was enriched compared to the CS for most cytokines (including IL-8 and MIP-1β) and soluble E-cadherin (sE-cadherin, an epithelial disruption marker), although CS levels of IL-1α and IL-1β were higher. Baseline total bacterial abundance was ≥ 20-fold higher in the CS than the urethra (median 27,100 vs. 1200 gene copies/swab, p = 0.001), and anaerobes comprised 58% of CS bacteria vs. 42% of urethral bacteria. PC did not alter urethral IL-8 (median 806 at baseline vs. 1130 pg/ml at 12 months; p = 0.062) and urethral sE-cadherin increased (113,223 vs. 158,385 pg/ml, p = 0.009), despite five- and sevenfold drops in total bacterial and anaerobe abundance after PC, respectively. However, PC dramatically reduced CS levels of sE-cadherin (15,843 vs. 837 pg/ml, p < 0.001) and most cytokines (IL-8; 34 vs. 3 pg/ml, p < 0.001), while reducing total bacterial and anaerobe abundance by 13-fold and 60-fold, respectively (both P ≤ 0.004). Conclusions The urethra is immunologically rich with characteristics of an HIV-susceptible tissue site. However, PC had no impact on urethral immunology and may have reduced epithelial integrity, despite modest reductions in total bacteria and anaerobes, suggesting that HIV protection from PC is not mediated via immune or microbiome alterations in the urethra. Video abstract

BackgroundIn sub-Saharan Africa (SSA), disclosure of HIV status to children remains low. Few studies have examined how children navigate and come to terms with their HIV status. The aim of this study was to explore experiences of children about disclosure of their HIV status.MethodsBetween October 2020 and July 2021, 18 purposively selected children aged between 12-17 whose HIV status had been disclosed to them by their caregivers or healthcare providers (HCPs) were recruited for this study. We conducted 18 in-depth interviews (IDIs) to collect data for this study. Data were analyzed using the semantic thematic analysis approach.ResultsPrimary data obtained through IDIs revealed that disclosure of HIV status to children occurred as a one-time event without pre-disclosure preparatory planning or focused post disclosure follow-up counseling irrespective of the discloser. Post disclosure psycho-social experiences elicited mixed responses. Some children experienced insults and belittlement and stigma and discrimination in the family and community for out-of-school children and at school for school-going children. Positive disclosure experiences involved receiving support to improve ART adherence through constantly being reminded to take their medications timely at the workplace, by supervisors, for working children and by teachers, at school for school-going children.ConclusionsThis research contributes to knowledge about children' s experiences of being HIV infected and can specifically be used to improve disclosure strategies.

Understanding treatment-seeking behavior is critical to the treatment and control of sexually transmitted infections (STIs), yet current data on STI treatment seeking in low-resource settings is rare. This population-based study aimed to describe STI treatment-seeking behavior and identify factors associated with seeking treatment at a clinic among adults with STI-related symptoms in rural Uganda. The STI prevalence study (STIPS) conducted a survey and STI testing among all consenting adults aged 18-49 in two communities in rural south-central Uganda. Of 1,825 participants, 962 individuals self-reported STI symptoms in the past six months; we present descriptive data on treatment seeking and STI prevalence among these individuals. We used multivariable Poisson regressions with robust variance to determine the sociodemographic and symptom-related factors independently associated with seeking STI treatment at a clinic and assessed the association with previous clinic treatment seeking and current STI diagnosis. Forty-three percent of adults who reported STI-related symptoms in the past six months said they did not seek any treatment. Among those who did, 58% sought treatment at a private clinic, 28% at a government clinic, 9% at a pharmacy/drug store, 3% at a traditional healer, 2% at a market/shop, and 5% at another location. Among both males and females, having multiple STI related symptoms was positively associated with clinic treatment seeking (males = PRR: 1.73, 95%CI: 1.36-2.21; females = PR: 1.41, 95%CI: 1.12-1.78). Approximately one-third of males and females who reported previously seeking clinic treatment for their symptoms were diagnosed with a curable STI at the time of the survey. In this setting, nearly half of adults with STI-related symptoms are not seeking clinical care and many who report having sought treatment for recent STI symptoms have curable STIs. Future studies should explore barriers to care-seeking and strategies to improve STI services.

Summary: 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

HIV prevalence varies throughout Africa, but the contribution of migration remains unclear. Using population-based data from ~22,000 persons, Grabowski et al. show that HIV-positive migrants selectively migrate to high prevalence areas and that out-migrants from these areas geographically disperse.

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.

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.

IntroductionUganda confirmed its first COVID-19 case in March 2020, leading to country-wide closures and a stay-at-home order. Infectious disease pandemics can overwhelm adaptive coping capacity (e.g., general self-efficacy and resilience) and increase the risk for mental distress. For individuals experiencing intimate partner violence (IPV) and cohabitating with a perpetrator, stay-at-home orders can also increase risk of violence, which can further exacerbate mental distress. The present study explores women's perceived self-efficacy and resilient coping, mental health outcomes (depression and COVID-19 related anxiety), hazardous alcohol use and IPV in the context of Uganda's national 2020 lockdown.MethodsA phone-based survey was undertaken from June-August of 2020 in Wakiso District, Uganda. The study sample consisted of Africa Medical and Behavioral Sciences Organization (AMBSO) Population Health Surveillance (APHS) study participants who agreed to be contacted for future research. The analytic sample was restricted to women aged 13-80 years. Bivariate analysis and multivariable models explored associations between experiences of IPV and measures of adaptive coping, mental health and alcohol use.ResultsA total of 556 women aged 13-79 years (mean age of 33.4 years) participated. Over half (55%) were currently married. The majority (60%) reported a decrease in alcohol use during the lockdown. Nearly half of the sample were experiencing physical or verbal IPV and reported an increase in violence during the lockdown. In adjusted analysis, alcohol use was associated with four times greater odds of recent physical IPV (aOR 4.06, 95% CI = 1.65-10.02, p = 0.0024), while participants had lower odds of experiencing any form of IPV as general self-efficacy increased (aOR 0.95, 95% CI = 0.91-0.99, p = 0.0308).ConclusionLockdown measures in Uganda may have mitigated increased alcohol consumption. IPV was exacerbated during lockdown; more than 2 in 5 IPV victims experienced increased physical or verbal violence. Development of programming and policies aimed at mitigating women's risk of IPV during future lockdowns are needed.

In Uganda, depression is a major public health issue. Psychometric assessment of translated depression measures is critical to public health planning to ensure proper screening, surveillance, and treatment of depression and related outcomes. We examined aspects of the validity and reliability of the Patient Health Questionnaire-9 (PHQ-9) translated into Luganda and Runyoro among Ugandan adolescents and adults. Data from the ongoing AMBSO Population Health Surveillance study were analyzed from the Wakiso and Hoima districts in Uganda. Descriptive statistics were calculated for the overall sample and stratified by translated language. Construct validity was assessed for each translated scale using confirmatory factor analysis for ordinal data. The internal consistency of each translated scale was assessed using Cronbach's alpha, McDonald's omega total and omega hierarchical. Both the Luganda- and Runyoro-translated PHQ-9 had similar sample means (3.46 [SD ​= ​3.26] and 3.58 [SD ​= ​3.00], respectively), supported a single-factor structure, and demonstrated satisfactory internal consistency (Cronbach's alpha of 0.73 and 0.72, respectively). Our preliminary findings indicate that the Luganda and Runyoro translations of the PHQ-9 had satisfactory construct validity and internal consistency in our sample. Future studies should expand on this promising work by assessing additional psychometric characteristics of these translated measures in other communities in Uganda.

Background: People living with HIV are at increased risk for cardiovascular disease (CVD). In sub-Saharan Africa, population-based data on major CVD events such as stroke and myocardial infarction are difficult to collect. The use of proxy measures could be a feasible way to better study CVD in such settings. This study aimed to determine the acceptance of incorporating ECG and arterial function measurements into a population-based cohort study and to assess the prevalence of ECG abnormalities and arterial stiffness. Methods: A pilot study was conducted within the Rakai Community Cohort Study in Uganda on two high-risk CVD populations; one determined by age (35–49) and Framingham CVD risk scores and the other by age alone (50+). Data on ECG, arterial function, blood pressure, and HIV status were collected. The acceptability of incorporating ECG and arterial function measurements was established as an acceptance rate difference of no more than 5% to blood pressure measurements. Results: A total of 118 participants were enrolled, 57 participants living with HIV and 61 HIV-negative participants. Both ECG measurements and arterial function were well accepted (2% difference). Left ventricular hypertrophy (LVH) and arterial stiffness (>10 m/s) were common in both participants living with HIV and HIV-negative participants across the two high-risk populations. Prevalence rates ranged from 30% to 53% for LVH and 25% to 58% for arterial stiffness. Arterial stiffness at the 11 m/s cutoff (p = 0.03) was found to be more common among participants living with HIV in the 35–49 population. Conclusions: The incorporation of ECG and arterial function measurements into routine activities of a population-based cohort was acceptable and incorporating these proxy measures into cohort studies should be explored further. LVH and arterial stiffness were both common irrespective of HIV status with arterial stiffness potentially more common among people living with HIV.

Here, Ratmann et al. show how viral deep sequencing data can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks.

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

Objectives This study aimed to determine the lifetime prevalence of male-perpetrated intimate partner violence (IPV), and to assess the association with food insecurity, sociodemographic factors and health risk behaviours in Uganda in the year preceding COVID-19-associated lockdowns.Design Population-based, cross-sectional household survey.Setting Urban, semiurban and rural communities of the Wakiso and Hoima districts in Uganda.Participants A total of N=2014 males aged 13–80 years participated in the survey. The current study included males who reported having ever been in a sexual union and responded to the IPV questions (N=1314).Measures Data were collected face-to-face from May 2018 to July 2019 using an interviewer-mediated questionnaire. Lifetime IPV perpetration was measured as ‘no physical and/or sexual IPV’, ‘physical’ versus ‘sexual violence only’, and ‘physical and sexual violence’. Past-year food insecurity was measured through the Food Insecurity Experience Scale and categorised into ‘none’, ‘low’ and ‘high’. Multinomial logistic regression was used to determine the crude and adjusted relative risk ratios (aRRRs) of IPV perpetration in relation to self-reported food insecurity, adjusting for sociodemographic and health risk behaviours.Results The prevalence of self-reported lifetime IPV perpetration was 14.6% for physical and 6.5% for sexual violence, while 5.3% reported to have perpetrated both physical and sexual IPV. Most (75.7%) males reported no food insecurity, followed by low (20.7%) and high (3.6%) food insecurity. In adjusted models, food insecurity was associated with increased risk of having perpetrated both physical and sexual violence (aRRR=2.57, 95% CI 1.52 to 4.32). IPV perpetration was also independently associated with having had more than one lifetime sexual partner and drinking alcohol, but not with education level or religion.Conclusion This study suggests that food insecurity is associated with male IPV perpetration, and more efforts are needed to prevent and mitigate the expected worsening of this situation as a result of the COVID-19 pandemic.

IntroductionAntenatal alcohol use is linked to adverse maternal and neonatal outcomes. Uganda has one of the highest rates of alcohol use in sub-Saharan Africa, but the prevalence of antenatal alcohol use has not been reported in the Rakai region.MethodsWe used cross-sectional data from pregnant women in the Rakai Community Cohort Study between March 2017 and September 2018. Using bivariate and multivariable analyses, we assessed associations between self-reported antenatal alcohol use and sociodemographic characteristics, intimate partner violence (IPV), and HIV status.ResultsAmong 960 pregnant women, the median age was 26 years, 35% experienced IPV in the past 12 months, 13% were living with HIV, and 33% reported alcohol use during their current pregnancy. After adjusting for marital status, education, smoking, and HIV status; Catholic religion (AOR: 3.54; 95% CI: 1.89-6.64; compared to other), bar/restaurant work (AOR: 2.40; 95% CI: 1.17-4.92; compared to agriculture), >one sex partner in past year (AOR: 1.92; 95% CI: 1.17-3.16), a partner that drank before sex in past year (AOR: 2.01; 95% CI: 1.48-2.74), and past year IPV (AOR: 1.55; 95% CI: 1.14-2.11) were associated with antenatal alcohol use.ConclusionWe found that alcohol use during pregnancy was common and associated with religion, occupation, higher numbers of past year sex partners, having a partner who drank before sex in the past 12 months, and IPV experience. More research is needed to understand the quantity, frequency, and timing of antenatal alcohol use; and potential impacts on neonates; and to identify services that are acceptable and effective among pregnant women.

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

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

IntroductionUganda has one of the highest rates of alcohol use in sub-Saharan Africa but prevalence and correlates of drinking are undocumented in the Rakai region, one of the earliest epicenters of the HIV/AIDS epidemic in East Africa.MethodsWe analyzed cross-sectional data from 18,700 persons (8,690 men, 10,010 women) aged 15-49 years, living in agrarian, trading and fishing communities and participating in the Rakai Community Cohort Study (RCCS) between March 2015 and September 2016. Logistic regression models assessed associations between past year alcohol use and sociodemographic characteristics, other drug use and HIV status, controlling for age, religion, education, occupation, marital status, and household socioeconomic status.ResultsPast year alcohol prevalence was 45%. Odds of drinking were significantly higher in men (versus women) and fishing communities (versus agrarian areas). Odds of drinking increased with age, previous (versus current) marriage and past year drug use. By occupation, highest odds of drinking were among fishermen and (in women) bar/restaurant workers. Alcohol-related consequences were more commonly reported by male (vs. females) drinkers, among whom up to 35% reported alcohol dependence symptoms (e.g., unsteady gait). HIV status was strongly associated with alcohol use in unadjusted but not adjusted models.ConclusionsAlcohol use differed by gender, community type and occupation. Being male, living in a fishing community and working as a fisherman or restaurant/bar worker (among women) were associated with higher odds of drinking. Alcohol reduction programs should be implemented in Uganda's fishing communities and among people working in high risk occupations (e.g., fishermen and restaurant/bar workers).

BackgroundThe rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment.MethodsWe carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect of a family economic empowerment (EE) intervention on viral suppression in five districuts in Uganda. In total, 39 accredited health care clinics from study districts with existing procedures tailored to adolescent adherence were eligible to participate in the trial. We used data from 288 youth with detectable HIV viral loads (VL) at baseline (158 -intervention group from 20 clinics, 130 -non-intervention group from 19 clinics). The primary end point was undetectable plasma HIV RNA levels, defined as < 40 copies/ml. We used Kaplan-Meier (KM) analysis and Cox proportional hazard models to estimate intervention effects.FindingsThe Kaplan-Meier (KM) analysis indicated that an incidence of undetectable VL (0.254) was significantly higher in the intervention condition compared to 0.173 (in non-intervention arm) translated into incidence rate ratio of 1.468 (CI: 1.064-2.038), p = 0.008. Cox regression results showed that along with the family-based EE intervention (adj. HR = 1.446, CI: 1.073-1.949, p = 0.015), higher number of medications per day had significant positive effects on the viral suppression (adj.HR = 1.852, CI: 1.275-2.690, p = 0.001).InterpretationA family economic empowerment intervention improved treatment success for ALWHIV in Uganda. Analyses of cost effectiveness and scalability are needed to advance incorporation of this intervention into routine practice in low and middle-income countries.

Abstract Background Although fishing communities have a significantly higher HIV prevalence than the general population, there is paucity of data on the burden of HIV and service utilization, particularly among the youth. We assessed the HIV prevalence and utilization of HIV prevention and treatment services among youth in Kasensero fishing community and the neighboring communities. Method Data were derived from the Rakai Community Cohort Study (RCCS) surveys conducted between 2013 and 2014. The RCCS is a population-based household survey that collects data annually from individuals aged 15–49 years, resident in 48 communities in Rakai and neighboring districts in Uganda. For this analysis, socio-demographic, behavioral and HIV-related data were obtained for 792 individuals aged 15–24 years. We used logistic regression to conduct bivariate and multivariable analysis to determine the factors that are independently associated with HIV-positive status and their corresponding 95% confidence intervals. Data were analyzed using STATA version 13. Results Overall HIV prevalence was 19.7% (n = 155); higher in Kasensero (n = 141; 25.1%) and Gwanda (n = 8; 11%) than in Kyebe (n = 6; 3.9%), p

IntroductionTetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV).ObjectiveTo determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision.MethodsWe enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response.ResultsMean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35-0.53) on day 0, 3.86IU/ml (CI 3.60-4.11) on day 14, 4.05IU/ml (CI 3.81-4.29) on day 28, and 4.48IU/ml (CI 4.28-4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years.ConclusionInsufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years.

ABSTRACT Sexual transmission of HIV requires exposure to the virus and infection of activated mucosal immune cells, specifically CD4+ T cells or dendritic cells. The foreskin is a major site of viral entry in heterosexual transmission of HIV. Although the probability of acquiring HIV from a sexual encounter is low, the risk varies even after adjusting for known HIV risk factors. The genital microbiome may account for some of the variability in risk by interacting with the host immune system to trigger inflammatory responses that mediate the infection of mucosal immune cells. We conducted a case-control study of uncircumcised participants nested within a randomized-controlled trial of male circumcision in Rakai, Uganda. Using penile (coronal sulcus) swabs collected by study personnel at trial enrollment, we characterized the penile microbiome by sequencing and real-time PCR and cytokine levels by electrochemiluminescence assays. The absolute abundances of penile anaerobes at enrollment were associated with later risk of HIV seroconversion, with a 10-fold increase in Prevotella, Dialister, Finegoldia, and Peptoniphilus increasing the odds of HIV acquisition by 54 to 63%, after controlling for other known HIV risk factors. Increased abundances of anaerobic bacteria were also correlated with increased cytokines, including interleukin-8, which can trigger an inflammatory response that recruits susceptible immune cells, suggesting a mechanism underlying the increased risk. These same anaerobic genera can be shared between heterosexual partners and are associated with increased HIV acquisition in women, pointing to anaerobic dysbiosis in the genital microbiome and an accompanying inflammatory response as a novel, independent, and transmissible risk factor for HIV infection. IMPORTANCE We found that uncircumcised men who became infected by HIV during a 2-year clinical trial had higher levels of penile anaerobes than uncircumcised men who remained HIV negative. We also found that having higher levels of penile anaerobes was also associated with higher production of immune factors that recruit HIV target cells to the foreskin, suggesting that anaerobes may modify HIV risk by triggering inflammation. These anaerobes are known to be shared by heterosexual partners and are associated with HIV risk in women. Therefore, penile anaerobes may be a sexually transmissible risk factor for HIV, and modifying the penile microbiome could potentially reduce HIV acquisition in both men and women.

Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before and after circumcision, and correlated with CD4 T cells subsets in foreskin tissue. HIV acquisition was associated with detectable coronal sulcus Interleukin-8 (IL-8 aOR 2.26, 95%CI 1.04-6.40) and Monokine Induced by γ-interferon (MIG aOR 2.72, 95%CI 1.15-8.06) at the visit prior to seroconversion, and the odds of seroconversion increased with detection of multiple cytokines. Coronal sulcus chemokine levels were not correlated with those in the vagina of a man's female sex partner. The detection of IL-8 in swabs was significantly reduced 6 months after circumcision (PRR 0.59, 95%CI 0.44-0.87), and continued to decline for at least two years (PRR 0.29, 95%CI 0.16-0.54). Finally, prepuce IL-8 correlated with increased HIV target cell density in foreskin tissues, including highly susceptible CD4 T cells subsets, as well as with tissue neutrophil density. Together, these data suggest that penile inflammation increases HIV susceptibility and is reduced by circumcision.

Evolutionary theory hypothesizes that intermediate virulence maximizes pathogen fitness as a result of a trade-off between virulence and transmission, but empirical evidence remains scarce. We bridge this gap using data from a large and long-standing HIV-1 prospective cohort, in Uganda. We use an epidemiological-evolutionary model parameterised with this data to derive evolutionary predictions based on analysis and detailed individual-based simulations. We robustly predict stabilising selection towards a low level of virulence, and rapid attenuation of the virus. Accordingly, set-point viral load, the most common measure of virulence, has declined in the last 20 years. Our model also predicts that subtype A is slowly outcompeting subtype D, with both subtypes becoming less virulent, as observed in the data. Reduction of set-point viral loads should have resulted in a 20% reduction in incidence, and a three years extension of untreated asymptomatic infection, increasing opportunities for timely treatment of infected individuals.

Background: The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but findings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women. Methods: In this prospective study, we enrolled HIV-negative and HSV2-negative women aged 15–49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984. Findings: Between Aug 11, 2003, and July 6, 2006, we enrolled 682 women in this study. We noted HSV2 seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using DMPA (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 (95% CI 1·09–4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49–26·3; p=0·012). Interpretation: Consistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These findings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly effective contraceptive methods is needed for women, particularly in sub-Saharan Africa. Funding: Bill and Melinda Gates Foundation, Doris Duke Charitable Foundation, US National Institutes of Health, and Fogarty International Center.

ABSTRACT Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and poor gynecologic and obstetric outcomes. Male circumcision reduces BV-associated bacteria on the penis and decreases BV in female partners, but the link between penile microbiota and female partner BV is not well understood. We tested the hypothesis that having a female partner with BV increases BV-associated bacteria in uncircumcised men. We characterized penile microbiota composition and density (i.e., the quantity of bacteria per swab) by broad-coverage 16S rRNA gene-based sequencing and quantitative PCR (qPCR) in 165 uncircumcised men from Rakai, Uganda. Associations between penile community state types (CSTs) and female partner's Nugent score were assessed. We found seven distinct penile CSTs of increasing density (CST1 to 7). CST1 to 3 and CST4 to 7 were the two major CST groups. CST4 to 7 had higher prevalence and abundance of BV-associated bacteria, such as Mobiluncus and Dialister, than CST1 to 3. Men with CST4 to 7 were significantly more likely to have a female partner with a high Nugent score (P = 0.03). Men with two or more extramarital partners were significantly more likely to have CST4 to 7 than men with only marital partners (CST4 to 7 prevalence ratio, 1.84; 95% confidence interval [CI], 1.16 to 2.92). Female partner Nugent BV is significantly associated with penile microbiota. Our data support the exchange of BV-associated bacteria through intercourse, which may explain BV recurrence and persistence. IMPORTANCE Bacterial vaginosis (BV) is sexually associated but not considered a sexually transmitted disease. Our findings suggest that the uncircumcised penis is an important niche for BV-associated genital anaerobes. In addition, we found a link between extramarital sexual relationships and BV-associated bacteria in men, which parallels earlier findings of the association between sexual activity and BV in women. This suggests the sexual transmissibility of BV-associated bacteria. Reducing bacterial exchange by barrier methods and managing carriage of BV-associated bacteria in men may decrease BV persistence and recurrence in women.

BackgroundA randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC.Methods and findingsHIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [ 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow-up for those who were not on ART at enrollment.ConclusionPenile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC.

In Kasensero fishing community, home of the first recorded case of HIV in Uganda, HIV transmission is still very high with an incidence of 4.3 and 3.1 per 100 person-years in women and men, respectively, and an HIV prevalence of 44%, reaching up to 74% among female sex workers. We explored drivers for the high HIV transmission at Kasensero from the perspective of fishermen and other community members to inform future policy and preventive interventions.20 in-depth interviews including both HIV positive and HIV negative respondents, and 12 focus-group discussions involving a total of 92 respondents from the Kasensero fishing community were conducted during April-September 2014. Content analysis was performed to identify recurrent themes.The socio-economic risk factors for high HIV transmission in Kasensero fishing community cited were multiple and cross-cutting and categorized into the following themes: power of money, risk denial, environmental triggers and a predisposing lifestyle and alcoholism and drug abuse. Others were: peer pressure, poor housing and the search for financial support for both the men and women which made them vulnerable to HIV exposure and or risk behavior.There is a need for context specific combination prevention interventions in Kasensero that includes the fisher folk and other influential community leaders. Such groups could be empowered with the knowledge and social mobilization skills to fight the negative and risky behaviors, perceptions, beliefs, misconceptions and submission attitudes to fate that exposes the community to high HIV transmission. There is also need for government/partners to ensure effective policy implementation, life jackets for all fishermen, improve the poor housing at the community so as to reduce overcrowding and other housing related predispositions to high HIV rates at the community. Work place AIDS-competence teams have been successfully used to address high HIV transmission in similar settings.

BACKGROUND: Medical male circumcision (MC) of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda. METHODS: 195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE). RESULTS: Of the 195 men, 129 had a CD4 count ≧ 350 and 66 had CD4

Targeting most-at-risk individuals with HIV preventive interventions is cost-effective. We developed gender-specific indices to measure risk of HIV among sexually active individuals in Rakai, Uganda.We used multivariable Cox proportional hazards models to estimate time-to-HIV infection associated with candidate predictors. Reduced models were determined using backward selection procedures with Akaike's information criterion (AIC) as the stopping rule. Model discrimination was determined using Harrell's concordance index (c index). Model calibration was determined graphically. Nomograms were used to present the final prediction models.We used samples of 7,497 women and 5,783 men. 342 new infections occurred among females (incidence 1.11/100 person years,) and 225 among the males (incidence 1.00/100 person years). The final model for men included age, education, circumcision status, number of sexual partners, genital ulcer disease symptoms, alcohol use before sex, partner in high risk employment, community type, being unaware of a partner's HIV status and community HIV prevalence. The Model's optimism-corrected c index was 69.1 percent (95% CI = 0.66, 0.73). The final women's model included age, marital status, education, number of sex partners, new sex partner, alcohol consumption by self or partner before sex, concurrent sexual partners, being employed in a high-risk occupation, having genital ulcer disease symptoms, community HIV prevalence, and perceiving oneself or partner to be exposed to HIV. The models optimism-corrected c index was 0.67 (95% CI = 0.64, 0.70). Both models were well calibrated.These indices were discriminative and well calibrated. This provides proof-of-concept that population-based HIV risk indices can be developed. Further research to validate these indices for other populations is needed.

To assess the safety and acceptance of the PrePex device for medical male circumcision (MMC) in rural Uganda.In an observational study, HIV-uninfected, uncircumcised men aged 18 and older who requested elective MMC were informed about the PrePex and dorsal slit methods and offered a free choice of their preferred procedure. 100 men received PrePex to assess preliminary safety (aim 1). An additional 329 men, 250 chose PrePex and 79 chose Dorsal slit, were enrolled following approval by the Safety Monitoring Committee (aim 2). Men were followed up at 7 days to assess adverse events (AEs) and to remove the PrePex device. Wound healing was assessed at 4 weeks, with subsequent weekly follow up until completed healing.The PrePex device was contraindicated in 5.7% of men due to a tight prepuce or phimosis/adhesions. Among 429 enrolled men 350 (82.0%) got the PrePex device and 79 (18.0%) the dorsal slit procedure. 250 of 329 men (76.0%) who were invited to choose between the 2 procedures chose Prepex. There were 9 AEs (2.6%) with the PrePex, of which 5 (1.4%) were severe complications, 4 due to patient self-removal of the device leading to edema and urinary obstruction requiring emergency surgical circumcision, and one due to wound dehiscence following device removal. 71.8% of men reported an unpleasant odor prior to PrePex removal. Cumulative rates of completed wound healing with the PrePex were 56.7% at week 4, 84.8% week 5, 97.6% week 6 and 98.6% week 7, compared to 98.7% at week 4 with dorsal slit (p