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.

Incidence of health facility switching and associations with HIV viral rebound among persons on antiretroviral therapy (ART) in Uganda: a population-based study.

BACKGROUND: A substantial fraction of persons on antiretroviral therapy (ART) considered lost to follow-up have actually transferred their HIV care to other facilities. However, the relationship between facility switching and virologic outcomes, including viral rebound, is poorly understood. METHODS: We used data from 40 communities (2015-2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. Persons aged 15-49 years with serologically confirmed HIV infection self-reporting ART use and contributing ≥1 follow-up visits were included. Facility switching and virologic outcomes were assessed between two consecutive study visits (i.e., index and follow-up visits, ∼18-month interval). Those reporting different HIV treatment facilities between index and follow-up study visits were classified as having switched facilities. Virologic outcomes included viral rebound among individuals initially suppressed (<200 copies/mL). Multivariable Poisson regression was used to estimate associations between facility switching and viral rebound. RESULTS: Overall, 2,257 persons self-reporting ART use (median age: 35 years, 65% women, 92% initially suppressed) contributed 3,335 visit-pairs and 5,959 person-years (py) to the analysis. Facility switching was common (4.8 per 100 py, 95%CI 4.2-5.5) and most pronounced in persons <30 years and fishing community residents. Among persons suppressed at their index visit (n=2,076), incidence of viral rebound was over twice as high in persons who switched facilities (adjIRR=2.27, 95%CI 1.16-4.45). CONCLUSIONS: Facility switching was common and associated with viral rebound among persons initially suppressed. Investments in more agile, person-centered models for mobile clients are needed to address system inefficiencies and bottlenecks that can disrupt HIV care continuity.

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

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

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

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

Uptake and retention on HIV pre-exposure prophylaxis among key and priority populations in South-Central Uganda.

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

Cell Phones, Sexual Behaviors and HIV Prevalence in Rakai, Uganda: A Cross Sectional Analysis of Longitudinal Data.

Cell phones have increased communication and connection across the globe and particularly in sub-Saharan Africa-with potential consequences for the HIV epidemic. We examined the association among ownership of cell phones, sexual behaviors (number of sexual partners, alcohol use before sex, inconsistent condom use), and HIV prevalence. Data were from four rounds (2010-2016) of the Rakai Community Cohort Study (N = 58,275). Sexual behaviors and HIV prevalence were compared between people who owned a cell phone to people who did not own a cell phone. We stratified analysis by younger (15-24 years) and older (25+ years) age groups and by gender. Using logistic regression and after adjusting for sociodemographic characteristics, we found cell phone ownership was independently associated with increased odds of having two or more sexual partners in the past 12 months across age and gender groups (young men AOR 1.67, 95% CI 1.47-1.90; young women AOR 1.28 95% CI 1.08-1.53; older men AOR 1.54 95% CI 1.41-1.69; older women AOR 1.44 95% CI 1.26-1.65). Interestingly, young men who owned cell phones had decreased odds of using condoms inconsistently (AOR 0.66, 95% CI 0.57-0.75). For young women, cell phone ownership was associated with increased odds of using alcohol before sex (AOR 1.38 95% CI 1.17-1.63) and increased odds of inconsistent condom use (AOR 1.40, 95% 1.17-1.67). After adjusting for sociodemographic characteristics, only young women who owned cell phones had increased odds of being HIV positive (AOR 1.27 95% CI 1.07-1.50). This association was not mediated by sexual behaviors (Adjusted for sociodemographic characteristics and sexual behaviors AOR 1.24, 95% CI 1.05-1.46). While cell phone ownership appears to be associated with increased HIV risk for young women, we also see a potential opportunity for future cell phone-based health interventions.

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.

Preference for Sayana® Press versus intramuscular Depo-Provera among HIV-positive women in Rakai, Uganda: a randomized crossover trial.

INTRODUCTION: Sayana Press (SP), a subcutaneous formulation of depot medroxyprogesterone acetate (DMPA) prefilled in a Uniject injection system, could potentially improve and expand contraceptive injection services, but acceptability of SP is unknown. HIV-positive women need contraception to avoid unintended pregnancy and risk of vertical HIV transmission. We assessed acceptability of SP versus intramuscular DMPA (DMPA-IM) among HIV-positive women and their care providers in Rakai, Uganda. METHODS: Women were randomized to DMPA-IM or SP at baseline, received the alternate product at 3 months, and chose their preferred method at 6 months. We determined preferences among new and experienced contraceptive injectable users who had tried both types of injection during the trial, and from providers before and after providing both types of injectables to clients. RESULTS: Among 357 women randomized, 314 were followed up at 6 months (88%). Although SP caused more skin irritation than DMPA-IM (3.8% vs. 0% at 6 months, p=.03), it was associated with marginally fewer side effects (30.4% vs. 40.4% at 6 months, p=.06). Participants reported high levels of willingness to recommend the DMPA contraception to a friend and satisfaction with the injection received, and these did not differ by injection type. Sixty-four percent of women and 73% of providers preferred SP to DMPA-IM at 6 months; women's preferences did not differ by previous experience with injectable contraception. CONCLUSIONS: SP is acceptable to HIV-positive women and health care providers in this rural Ugandan population. IMPLICATIONS: SP appears to be acceptable to HIV-positive women and their care providers in Rakai, Uganda, and strategies for appropriate rollout of this innovative technology should be explored.