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.

Prevalence and risk factors of metabolic dysfunction-associated steatotic liver disease in south Central Uganda: A cross-sectional survey.

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

Mortality Among HIV-Infected Adults on Antiretroviral Therapy in Southern Uganda.

BACKGROUND: Monitoring and evaluation of clinical programs requires assessing patient outcomes. Numerous challenges complicate these efforts, the most insidious of which is loss to follow-up (LTFU). LTFU is a composite outcome, including individuals out of care, undocumented transfers, and unreported deaths. Incorporation of vital status information from routine patient outreach may improve the mortality estimates for those LTFU. SETTINGS: We analyzed routinely collected clinical and patient tracing data for individuals (15 years or older) initiating antiretroviral treatment between January 2014 and December 2018 at 2 public HIV care clinics in greater Rakai, Uganda. METHODS: We derived unadjusted mortality estimates using Kaplan-Meier methods. Estimates, adjusted for unreported deaths, applied weighting through the Frangakis and Rubin method to represent outcomes among LTFU patients who were successfully traced and for whom vital status was ascertained. Confidence intervals were determined through bootstrap methods. RESULTS: Of 1969 patients with median age at antiretroviral treatment initiation of 31 years (interquartile range: 25-38), 1126 (57.2%) were female patients and 808 (41%) were lost. Of the lost patients, 640 patient files (79.2%) were found and reviewed, of which 204 (31.8%) had a tracing attempt. Within the electronic health records of the program, 28 deaths were identified with an estimated unadjusted mortality 1 year after antiretroviral treatment initiation of 2.5% (95% CI: 1.8% to 3.3%). Using chart review and patient tracing data, an additional 24 deaths (total 52) were discovered with an adjusted 1-year mortality of 3.8% (95% CI: 2.6% to 5.0%). CONCLUSIONS: Data from routine outreach efforts by HIV care and treatment programs can be used to support plausible adjustments to estimates of client mortality. Mortality estimates without active ascertainment of vital status of LTFU patients may significantly underestimate program mortality.

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.

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.

ECG Abnormalities and Arterial Stiffness by HIV Status among High-Risk Populations in Rakai, Uganda: A Pilot Study.

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.

Alcohol use during pregnancy in Rakai, Uganda.

INTRODUCTION: Antenatal 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. METHODS: We 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. RESULTS: Among 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. CONCLUSION: We 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.

Age patterns of HIV incidence in eastern and southern Africa: a modelling analysis of observational population-based cohort studies.

BACKGROUND: As the HIV epidemic in sub-Saharan Africa matures, evidence about the age distribution of new HIV infections and how this distribution has changed over the epidemic is needed to guide HIV prevention. We aimed to assess trends in age-specific HIV incidence in six population-based cohort studies in eastern and southern Africa, reporting changes in mean age at infection, age distribution of new infections, and birth cohort cumulative incidence. METHODS: We used a Bayesian model to reconstruct age-specific HIV incidence from repeated observations of individuals' HIV serostatus and survival collected among population HIV cohorts in rural Malawi, South Africa, Tanzania, Uganda, and Zimbabwe, in a collaborative analysis of the ALPHA network. We modelled HIV incidence rates by age, time, and sex using smoothing splines functions. We estimated incidence trends separately by sex and study. We used estimated incidence and prevalence results for 2000-17, standardised to study population distribution, to estimate mean age at infection and proportion of new infections by age. We also estimated cumulative incidence (lifetime risk of infection) by birth cohort. FINDINGS: Age-specific incidence declined at all ages, although the timing and pattern of decline varied by study. The mean age at infection was higher in men (cohort mean 27·8-34·6 years) than in women (24·8-29·6 years). Between 2000 and 2017, the mean age at infection per cohort increased slightly: 0·5 to 2·8 years among men and -0·2 to 2·5 years among women. Across studies, between 38% and 63% (cohort medians) of the infections in women were among those aged 15-24 years and between 30% and 63% of infections in men were in those aged 20-29 years. Lifetime risk of HIV declined for successive birth cohorts. INTERPRETATION: HIV incidence declined in all age groups and shifted slightly to older ages. Disproportionate new HIV infections occur among women aged 15-24 years and men aged 20-29 years, supporting focused prevention in these groups. However, 40-60% of infections were outside these ages, emphasising the importance of providing appropriate HIV prevention to adults of all ages. FUNDING: Bill & Melinda Gates Foundation.

Transactional Sex, Alcohol Use and Intimate Partner Violence Against Women in the Rakai Region of Uganda.

Transactional sex (TS) is prevalent in sub-Saharan Africa. Women's engagement in TS is linked with HIV infection; little is known about the relationship between TS, intimate partner violence (IPV) and alcohol use-established HIV risk behaviors. Using modified Poisson regression, we assessed associations between TS and physical, verbal and sexual IPV among 8248 women (15-49 years) who participated in the Rakai Community Cohort Study across forty communities in Uganda. An interaction term assessed moderation between alcohol use and TS and no significant interaction effects were found. In adjusted analysis, alcohol use and TS were significantly associated with all forms of IPV. In stratified analysis, TS was only associated with IPV in agrarian communities; alcohol use was not associated with physical IPV in trade communities or sexual IPV in trade and fishing communities. Identifying differences in IPV risk factors by community type is critical for the development of tailored interventions.

RESUMEN: El sexo transaccional (ST) es frecuente en África subsahariana. La participación de las mujeres en el ST está relacionada con la infección por VIH; Se sabe poco sobre la relación entre el ST, la violencia de pareja íntima (VPI) y el consumo de alcohol: conductas de riesgo establecidas para el VIH. Utilizando la regresión de Poisson modificada, evaluamos las asociaciones entre el ST y la VPI física, verbal y sexual entre 8,248 mujeres (15-49 años) que participaron en el Estudio de cohorte de la comunidad Rakai en cuarenta comunidades de Uganda. Un término de interacción evaluó la moderación entre el consumo de alcohol y el ST y no se encontraron efectos de interacción significativos. En el análisis ajustado, el consumo de alcohol y el ST se asociaron significativamente con todas las formas de VPI. En el análisis estratificado, el ST solo se asoció con la VPI en las comunidades agrarias; El consumo de alcohol no se asoció con la VPI física en las comunidades comerciales ni con la VPI sexual en las comunidades comerciales y pesqueras. Identificar las diferencias en los factores de riesgo de la violencia de género por tipo de comunidad es fundamental para el desarrollo de intervenciones personalizadas.

Prevalence and correlates of men's and women's alcohol use in agrarian, trading and fishing communities in Rakai, Uganda.

INTRODUCTION: Uganda 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. METHODS: We 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. RESULTS: Past 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. CONCLUSIONS: Alcohol 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).

Migration, hotspots, and dispersal of HIV infection in Rakai, Uganda.

HIV prevalence varies markedly throughout Africa, and it is often presumed areas of higher HIV prevalence (i.e., hotspots) serve as sources of infection to neighboring areas of lower prevalence. However, the small-scale geography of migration networks and movement of HIV-positive individuals between communities is poorly understood. Here, we use population-based data from ~22,000 persons of known HIV status to characterize migratory patterns and their relationship to HIV among 38 communities in Rakai, Uganda with HIV prevalence ranging from 9 to 43%. We find that migrants moving into hotspots had significantly higher HIV prevalence than migrants moving elsewhere, but out-migration from hotspots was geographically dispersed, contributing minimally to HIV burden in destination locations. Our results challenge the assumption that high prevalence hotspots are drivers of transmission in regional epidemics, instead suggesting that migrants with high HIV prevalence, particularly women, selectively migrate to these areas.

Population-level adult mortality following the expansion of antiretroviral therapy in Rakai, Uganda.

There are limited data on the impact of antiretroviral therapy (ART) on population-level adult mortality in sub-Saharan Africa. We analysed data for 2000-14 from the Rakai Community Cohort Study (RCCS) in Uganda, where free ART was scaled up after 2004. Using non-parametric and parametric (Weibull) survival analysis, we estimated trends in average person-years lived between exact ages 15 and 50, per capita life-years lost to HIV, and the mortality hazards of people living with HIV (PLHIV). Between 2000 and 2014, average adult life-years lived before age 50 increased significantly, from 26.4 to 33.5 years for all women and from 28.6 to 33.8 years for all men. As of 2014, life-years lost to HIV had declined significantly, to 1.3 years among women and 0.4 years among men. Following the roll-out of ART, mortality reductions among PLHIV were initially larger in women than men, but this is no longer the case.

Sexual risk behaviors following circumcision among HIV-positive men in Rakai, Uganda.

OBJECTIVE: To determine whether circumcision of HIV-positive men is associated with increased subsequent sexual risk behaviors which may place their female partners at risk. METHODS: Newly circumcised and uncircumcised HIV-positive men in the Rakai Community Cohort Study were followed from baseline (July 2013-January 2015) to determine trend in sexual risk behaviors and association of circumcision with subsequent sexual risk behaviors at follow up (February 2015-September 2016). Risk behaviors included sexual activity, alcohol before sex, transactional sex, multiple sex partners, casual sex partners, and inconsistent condom use with casual partners. The association was evaluated using modified Poisson regression, and sensitivity analyses were performed after multiple imputation with chained equations for missing data. RESULTS: We identified 538 eligible men, of whom 113(21.0%) were circumcised at baseline and 425(79.0%) were uncircumcised. Men in fishing communities were more likely to be circumcised (p = 0.032) as well as those exposed to targeted HIV messaging (p < 0.001). Overall, 188(34.9%) men were lost to follow up and most were uncircumcised (p = 0.020). Among those followed up, behaviors remained largely unchanged with no differences by circumcision status. Transactional sex appeared to be associated with circumcision in unadjusted analyses (PR = 1.58, 95%CI = 1.01,2.48; p = 0.045, p = 0.05) and adjusted analyses (adj.PR = 1.54, 95%CI = 1.06,2.23; p = 0.022). However, the association was no longer significant in sensitivity analyses after accounting for loss to follow up (adj.PR = 1.43, 95%CI = 0.98,2.08; p = 0.066). No association with circumcision was observed for other sexual risk behaviors. CONCLUSION: We found no association between circumcision of HIV-positive men and subsequent sexual risk behavior.

Efficacy of knowledge and competence-based training of non-physicians in the provision of early infant male circumcision using the Mogen clamp in Rakai, Uganda.

OBJECTIVE: To assess acquisition of knowledge and competence in performing Early Infant Male Circumcision (EIMC) by non-physicians trained using a structured curriculum. SUBJECTS AND METHODS: Training in provision of EIMC using the Mogen clamp was conducted for 10 Clinical Officers (COs) and 10 Registered Nurse Midwives (RNMWs), in Rakai, Uganda. Healthy infants whose mothers consented to study participation were assigned to the trainees, each of whom performed at least 10 EIMCs. Ongoing assessment and feedback for competency were done, and safety assessed by adverse events. RESULTS: Despite similar baseline knowledge, COs acquired more didactic knowledge than RNMWs (P = 0.043). In all, 100 EIMCs were assessed for gain in competency. The greatest improvement in competency was between the first and third procedures, and all trainees achieved 80% competency and retention of skills by the seventh procedure. The median (interquartile range) time to complete a procedure was 14.5 (10-47) min for the COs, and 15 (10-50) min for the RNMWs (P = 0.180). The procedure times declined by 2.2 min for each subsequent EIMC (P = 0.005), and rates of improvement were similar for COs and RNMWs. Adverse events were comparable between providers (3.5%), of which 1% were of moderate severity. CONCLUSION: Competence-based training of non-physicians improved knowledge and competency in EIMC performed by COs and RNMWs in Uganda.

Randomised trial of early infant circumcision performed by clinical officers and registered nurse midwives using the Mogen clamp in Rakai, Uganda.

OBJECTIVES: To assess the safety and acceptability of early infant circumcision (EIC) provided by trained clinical officers (COs) and registered nurse midwives (RNMWs) in rural Uganda. SUBJECTS AND METHODS: We conducted a randomised trial of EIC using the Mogen clamp provided by newly trained COs and RNMWs in four health centres in rural Rakai, Uganda. The trial was registered with clinicaltrials.gov # NCT02596282. In all, 501 healthy neonates aged 1-28 days with normal birth weight and gestational age were randomised to COs (n = 256) and RNMWs (n = 245) for EIC, and were followed-up at 1, 7 and 28 days. RESULTS: In all, 701 mothers were directly invited to participate in the trial, 525 consented to circumcision (74.9%) and 23 were found ineligible on screening (4.4%). The procedure took an average of 10.5 min. Adherence to follow-up was >90% at all scheduled visits. The rates of moderate/severe adverse events were 2.4% for COs and 1.6% for RNMWs (P = 0.9). All wounds were healed by 28 days after circumcision. Maternal satisfaction with the procedure was 99.6% for infants circumcised by COs and 100% among infants circumcised by RNMWs. CONCLUSIONS: EIC was acceptable in this rural Ugandan population and can be safely performed by RNMWs who have direct contact with the mothers during pregnancy and delivery. EIC services should be made available to parents who are interested in the service.

The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA): Data on mortality, by HIV status and stage on the HIV care continuum, among the general population in seven longitudinal studies between 1989 and 2014.

Timely progression of people living with HIV (PLHIV) from the point of infection through the pathway from diagnosis to treatment is important in ensuring effective care and treatment of HIV and preventing HIV-related deaths and onwards transmission of infection.  Reliable, population-based estimates of new infections are difficult to obtain for the generalised epidemics in sub-Saharan Africa.  Mortality data indicate disease burden and, if disaggregated along the continuum from diagnosis to treatment, can also reflect the coverage and quality of different HIV services.  Neither routine statistics nor observational clinical studies can estimate mortality prior to linkage to care nor following disengagement from care.  For this, population-based data are required. The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa brings together studies in Kenya, Malawi, South Africa, Tanzania, Uganda, and Zimbabwe.  Eight studies have the necessary data to estimate mortality by HIV status, and seven can estimate mortality at different stages of the HIV care continuum.  This data note describes a harmonised dataset containing anonymised individual-level information on survival by HIV status for adults aged 15 and above. Among PLHIV, the dataset provides information on survival during different periods: prior to diagnosis of infection; following diagnosis but before linkage to care; in pre-antiretroviral treatment (ART) care; in the first six months after ART initiation; among people continuously on ART for 6+ months; and among people who have ever interrupted ART.

Mortality trends in the era of antiretroviral therapy: evidence from the Network for Analysing Longitudinal Population based HIV/AIDS data on Africa (ALPHA).

BACKGROUND: The rollout of antiretroviral therapy (ART) is one of the largest public health interventions in Eastern and Southern Africa of recent years. Its impact is well described in clinical cohort studies, but population-based evidence is rare. METHODS: We use data from seven demographic surveillance sites that also conduct community-based HIV testing and collect information on the uptake of HIV services. We present crude death rates of adults (aged 15-64) for the period 2000-2011 by sex, HIV status, and treatment status. Parametric survival models are used to estimate age-adjusted trends in the mortality rates of people living with HIV (PLHIV) before and after the introduction of ART. RESULTS: The pooled ALPHA Network dataset contains 2.4 million person-years of follow-up time, and 39114 deaths (6893 to PLHIV). The mortality rates of PLHIV have been relatively static before the availability of ART. Mortality declined rapidly thereafter, with typical declines between 10 and 20% per annum. Compared with the pre-ART era, the total decline in mortality rates of PLHIV exceeds 58% in all study sites with available data, and amounts to 84% for women in Masaka (Uganda). Mortality declines have been larger for women than for men; a result that is statistically significant in five sites. Apart from the early phase of treatment scale up, when the mortality of PLHIV on ART was often very high, mortality declines have been observed in PLHIV both on and off ART. CONCLUSION: The expansion of treatment has had a large and pervasive effect on adult mortality. Mortality declines have been more pronounced for women, a factor that is often attributed to women's greater engagement with HIV services. Improvements in the timing of ART initiation have contributed to mortality reductions in PLHIV on ART, but also among those who have not (yet) started treatment because they are increasingly selected for early stage disease.

Mortality in women of reproductive age in rural South Africa.

OBJECTIVE: To determine causes of death and associated risk factors in women of reproductive age in rural South Africa. METHODS: Deaths and person-years of observation (pyo) were determined for females (aged 15-49 years) resident in 15,526 households in a rural South African Demographic and Health Surveillance site from 2000 to 2009. Cause of death was ascertained by verbal autopsy and ICD-10 coded; causes were categorized as HIV/TB, non-communicable, communicable/maternal/perinatal/nutrition, injuries, and undetermined (unknown). Characteristics of women were obtained from regularly updated household visits, while HIV and self-reported health status was obtained from the annual HIV surveillance. Overall and cause-specific mortality rates (MRs) with 95% confidence intervals (CI) were calculated. The Weibull regression model (HR, 95%CI) was used to determine risk factors associated with mortality. RESULTS: A total of 42,703 eligible women were included; 3,098 deaths were reported for 212,607 pyo. Overall MRwas 14.6 deaths/1,000 pyo (95% CI: 14.1-15.1), peaking in 2003 (MR 18.2/1,000 pyo, 95% CI: 16.4-20.1) and declining thereafter (2009: MR 9.6/1,000 pyo, 95% CI: 8.410.9). Mortality was highest for HIV/TB (MR 10.6/1,000 pyo, 95% CI: 10.211.1), accounting for 73.1% of all deaths, ranging from 61.2% in 2009 to 82.7% in 2002. Adjusting for education level, marital status, age, employment status, area of residence, and migration, all-cause mortality was associated with external migration (adjusted hazard ratio, or aHR), 1.70, 95% CI: 1.41-2.05), self-reported poor health status (aHR 8.26, 95% CI: 2.94-23.15), and HIV-infection (aHR 7.84, 95% CI: 6.26-9.82); external migration and HIV infection were also associated with causes of mortality other than HIV/TB (aHR 1.62 CI: 1.12-2.34 and aHR 2.59, CI: 1.79-3.75). CONCLUSION: HIV/TB was the leading cause of death among women of reproductive age, although rates declined with the rollout of HIV treatment in the area from 2004. Women's age, external migration status, and HIV-positive status were significantly associated with all-cause and cause-specific mortality.