Prevalence of Sexual Experience and Initiation of Sexual Intercourse Among Adolescents, Rakai District, Uganda, 1994-2011.

PURPOSE: The purpose of the study was to identify risk factors and time trends for sexual experience and sexual debut in rural Uganda. METHODS: Using population-based, longitudinal data from 15- to 19-year olds in Rakai, Uganda, we examined temporal trends in the prevalence of sexual experience and potential risk factors for sexual experience (n = 31,517 person-round observations) using logistic regression. We then identified factors associated with initiation of sex between survey rounds, using Poisson regression to estimate incidence rate ratios (IRR; n = 5,126 person-year observations). RESULTS: Sexual experience was more common among adolescent women than men. The prevalence of sexual experience rose for most age-gender groups after 1994 and then declined after 2002. Factors associated with higher prevalence of sexual experience (without adjustment for other factors) included age, not enrolled in school, orphanhood, lower socioeconomic status, and drinking alcohol in the past 30 days; similar factors were associated with initiation of sex. Factors independently associated with initiation of sex included older age, nonenrollment in school (IRR = 1.7 for women and 1.8 for men), alcohol use (IRR = 1.3 for women and men), and being a double orphan among men (IRR = 1.2). Sexual experience began to decline around 2000, whereas increases in school enrollment began as early as 1994 and declines in orphanhood occurred after 2004 (as antiretroviral therapy became available). CONCLUSIONS: Sexual experience among youth in Rakai was associated with social factors particularly school enrollment. Changes in these social factors also appear to influence change over time in sexual experience.

Rising School Enrollment and Declining HIV and Pregnancy Risk Among Adolescents in Rakai District, Uganda, 1994-2013.

BACKGROUND: Poverty, family stability, and social policies influence the ability of adolescents to attend school. Likewise, being enrolled in school may shape an adolescent's risk for HIV and pregnancy. We identified trends in school enrollment, factors predicting school enrollment (antecedents), and health risks associated with staying in or leaving school (consequences). METHODS: Data from the Rakai Community Cohort Study (RCCS) were examined for adolescents 15-19 years (n=21,735 person-rounds) from 1994 to 2013. Trends, antecedents, and consequences were assessed using logistic and linear regression with robust variance estimation. Qualitative data were used to explore school leaving among HIV+ and HIV- youth (15-24 years). RESULTS: School enrollment and socioeconomic status (SES) rose steadily from 1994 to 2013 among adolescents; orphanhood declined after availability of antiretroviral therapy. Antecedent factors associated with school enrollment included age, SES, orphanhood, marriage, family size, and the percent of family members <20 years. In qualitative interviews, youth reported lack of money, death of parents, and pregnancy as primary reasons for school dropout. Among adolescents, consequences associated with school enrollment included lower HIV prevalence, prevalence of sexual experience, and rates of alcohol use and increases in consistent condom use. Young women in school were more likely to report use of modern contraception and never being pregnant. Young men in school reported fewer recent sexual partners and lower rates of sexual concurrency. CONCLUSIONS: Rising SES and declining orphanhood were associated with rising school enrollment in Rakai. Increasing school enrollment was associated with declining risk for HIV and pregnancy.

Durable Suppression of HIV-1 after Virologic Monitoring-Based Antiretroviral Adherence Counseling in Rakai, Uganda.

OBJECTIVES: HIV viral load is recommended for monitoring antiretroviral treatment and identifying treatment failure. We assessed the durability of viral suppression after viral load-triggered adherence counseling among patients with HIV viremia 6 months after ART initiation. DESIGN: Observational cohort enrolled in an antiretroviral treatment program in rural Uganda. METHODS: Participants who underwent routine viral load determination every 24 weeks and had at least 48 weeks of follow-up were included in this analysis. Patients with viral loads >400 copies/ml at 24 weeks of treatment were given additional adherence counseling, and all patients were followed to assess the duration of viral suppression and development of virologic failure. RESULTS: 1,841 participants initiating antiretroviral therapy were enrolled in the Rakai Health Sciences Program between June 2005 and June 2011 and were followed with viral load monitoring every 24 weeks. 148 (8%) of patients did not achieve viral suppression at 24 weeks and were given additional adherence counseling. 85 (60%) of these patients had undetectable viral loads at 48 weeks, with a median duration of viral suppression of 240 weeks (IQR 193-288 weeks). Failure to achieve an undetectable viral load at 48 weeks was associated with age <30 years and 24 week viral load >2,000 copies/ml in multivariate logistic regression analysis. CONCLUSIONS: The majority of patients with persistent viremia who were provided adherence counseling achieved robust viral suppression for a median 4.6 years. Access to virologic monitoring and adherence counseling is a priority in resource-limited settings.

Behavioral, biological, and demographic risk and protective factors for new HIV infections among youth in Rakai, Uganda.

BACKGROUND: Prevalence of HIV infection is considerable among youth, although data on risk factors for new (incident) infections are limited. We examined incidence of HIV infection and risk and protective factors among youth in rural Uganda, including the role of gender and social transitions. METHODS: Participants were sexually experienced youth (15-24 years old) enrolled in the Rakai Community Cohort Study, 1999-2008 (n = 6741). Poisson regression with robust standard errors was used to estimate incident rate ratios (IRR) and 95% confidence intervals (CI) of incident HIV infection. RESULTS: HIV incidence was greater among young women than young men (14.1 vs. 8.3 per 1000 person-years, respectively); this gender disparity was greater among teenagers (14.9 vs. 3.6). Beyond behavioral (multiple partners and concurrency) and biological factors (sexually transmitted infection symptoms), social transitions such as marriage and staying in school influenced HIV risk. In multivariate analyses among women, HIV incidence was associated with living in a trading village (adjusted IRR (aIRR) = 1.48; 95% CI: 1.04 to 2.11), being a student (aIRR = 0.22; 95% CI: 0.07 to 0.72), current marriage (aIRR = 0.55; 95% CI: 0.37 to 0.81), former marriage (aIRR = 1.73; 95% CI: 1.01 to 2.96), having multiple partners, and sexually transmitted infection symptoms. Among men, new infections were associated with former marriage (aIRR = 5.57; 95% CI: 2.51 to 12.36), genital ulceration (aIRR = 3.56; 95% CI: 1.97 to 6.41), and alcohol use (aIRR = 2.08; 95% CI: 1.15 to 3.77). CONCLUSIONS: During the third decade of the HIV epidemic in Uganda, HIV incidence remains considerable among youth, with young women particularly at risk. The risk for new infections was strongly shaped by social transitions such as leaving school, entrance into marriage, and marital dissolution; the impact of marriage was different for young men than women.

Traditional herbal medicine use associated with liver fibrosis in rural Rakai, Uganda.

BACKGROUND: Traditional herbal medicines are commonly used in sub-Saharan Africa and some herbs are known to be hepatotoxic. However little is known about the effect of herbal medicines on liver disease in sub-Saharan Africa. METHODS: 500 HIV-infected participants in a rural HIV care program in Rakai, Uganda, were frequency matched to 500 HIV-uninfected participants. Participants were asked about traditional herbal medicine use and assessed for other potential risk factors for liver disease. All participants underwent transient elastography (FibroScan®) to quantify liver fibrosis. The association between herb use and significant liver fibrosis was measured with adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CI) using modified Poisson multivariable logistic regression. RESULTS: 19 unique herbs from 13 plant families were used by 42/1000 of all participants, including 9/500 HIV-infected participants. The three most-used plant families were Asteraceae, Fabaceae, and Lamiaceae. Among all participants, use of any herb (adjPRR = 2.2, 95% CI 1.3-3.5, p = 0.002), herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 2.9-8.7, p<0.001), and herbs from the Lamiaceae family (adjPRR = 3.4, 95% CI 1.2-9.2, p = 0.017) were associated with significant liver fibrosis. Among HIV infected participants, use of any herb (adjPRR = 2.3, 95% CI 1.0-5.0, p = 0.044) and use of herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 1.7-14.7, p = 0.004) were associated with increased liver fibrosis. CONCLUSIONS: Traditional herbal medicine use was independently associated with a substantial increase in significant liver fibrosis in both HIV-infected and HIV-uninfected study participants. Pharmacokinetic and prospective clinical studies are needed to inform herb safety recommendations in sub-Saharan Africa. Counseling about herb use should be part of routine health counseling and counseling of HIV-infected persons in Uganda.

High prevalence of liver fibrosis associated with HIV infection: a study in rural Rakai, Uganda.

BACKGROUND: Liver disease is a leading cause of mortality among HIV-infected persons in the United States and Europe. However, data regarding the effects of HIV and antiretroviral therapy (ART) on liver disease in Africa are sparse. METHODS: A total of 500 HIV-infected participants in an HIV care programme in rural Rakai, Uganda were frequency-matched by age, gender and site to 500 HIV-uninfected participants in a population cohort. All participants underwent transient elastography (FibroScan(®)) to quantify liver stiffness measurements (LSM) and identify participants with significant liver fibrosis, defined as LSM≥9.3 kPa (≈ Metavir F≥2). Risk factors for liver fibrosis were identified by estimating adjusted prevalence risk ratios (adjPRR) and 95% CI using modified Poisson multivariate regression. RESULTS: The prevalence of hepatitis B coinfection in the study population was 5%. The prevalence of significant fibrosis was 17% among HIV-infected and 11% in HIV-uninfected participants (P=0.008). HIV infection was associated with a 50% increase in liver fibrosis (adjPRR 1.5, 95% CI 1.1-2.1; P=0.010). Fibrosis was also associated with male gender (adjPRR 1.4, 95% CI 1.0-1.9; P=0.045), herbal medicine use (adjPRR 2.0, 95% CI 1.2-3.3; P=0.005), heavy alcohol consumption (adjPRR 2.3, 95% CI 1.3-3.9; P=0.005), occupational fishing (adjPRR 2.5, 95% CI 1.2-5.3; P=0.019) and chronic HBV infection (adjPRR 1.7, 95% CI 1.0-3.1; P=0.058). Among HIV-infected participants, ART reduced fibrosis risk (adjPRR 0.6, 95% CI 0.4-1.0; P=0.030). CONCLUSIONS: The burden of liver fibrosis among HIV-infected rural Ugandans is high. These data suggest that liver disease may represent a significant cause of HIV-related morbidity and mortality in Africa.

Hepatitis B virus and sexual behavior in Rakai, Uganda.

HIV and hepatitis B virus (HBV) co-infection poses important public health considerations in resource-limited settings. Demographic data and sera from adult participants of the Rakai Health Sciences Program Cohort in Southwestern Uganda were examined to determine HBV seroprevalence patterns in this area of high HIV endemicity prior to the introduction of anti-retroviral therapy. Commercially available EIAs were used to detect prevalent HBV infection (positive for HBV core antibody [anti-HBc] and/or positive HBV surface antigen [HBsAg]), and chronic infection (positive for HBsAg). Of 438 participants, 181 (41%) had prevalent HBV infection while 21 (5%) were infected chronically. Fourteen percent of participants were infected with HIV. Fifty three percent showed evidence of prevalent HBV infection compared to 40% among participants infected with HIV (P = 0.067). Seven percent of participants infected with HIV were HBsAg positive compared to 4% among participants not infected with HIV (P = 0.403). The prevalence of prevalent HBV infection was 55% in adults aged >50 years old, and 11% in persons under 20 years. In multivariable analysis, older age, HIV status, and serologic syphilis were significantly associated with prevalent HBV infection. Transfusion status and receipt of injections were not significantly associated with HBV infection. Contrary to expectations that HBV exposure in Uganda occurred chiefly during childhood, prevalent HBV infection was found to increase with age and was associated sexually transmitted diseases (HIV and syphilis.) Therefore vaccination against HBV, particularly susceptible adults with HIV or at risk of HIV/STDs should be a priority.

Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study.

OBJECTIVE: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population. METHODS: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology. RESULTS: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials. In line with trial observations, the projected HIV impacts were larger for the ST intervention in Mwanza than for the MT intervention in Rakai or the IEC and IEC + ST interventions in Masaka. All 4 simulated intervention strategies were more effective in reducing incidence of HIV infection in Mwanza than in either Rakai or Masaka. CONCLUSIONS: Population differences in sexual behavior, curable STD rates, and HIV epidemic stage can explain most of the contrast in HIV impact observed between the 3 trials. This study supports the hypothesis that STD management is an effective HIV prevention strategy in populations with a high prevalence of curable STDs, particularly in an early HIV epidemic.

Higher risk behaviour and rates of sexually transmitted diseases in Mwanza compared to Uganda may help explain HIV prevention trial outcomes.

OBJECTIVE: To determine to what extent the higher impact of treatment for sexually transmitted diseases (STD) on HIV incidence in Mwanza, Tanzania than in Rakai and Masaka, Uganda might be explained by baseline differences between the trial populations. DESIGN: A re-analysis of baseline data from the three trial populations comparing demography, sexual risk behaviour and HIV/STD epidemiology. METHODS: Data were compared after age-standardization and adjustments for sample selection where necessary. STD rates were also adjusted for the sensitivities and specificities of the diagnostic techniques used. RESULTS: Demographic patterns were similar across populations, apart from effects of AIDS on fertility and mortality (including widowhood) in Uganda. Higher sexual risk behaviours, including younger age of sexual debut, higher numbers of recent partners and lower frequency of condom use, were apparent in Mwanza compared to Masaka and Rakai. High-titre serological syphilis, gonorrhoea, chlamydia infection and trichomoniasis were all more prevalent in Mwanza, except for chlamydia infection in males. There was little difference between sites in the seroprevalence of Herpes simplex virus type-2. Age patterns in the prevalence of short-duration STD and current risk behaviours were similar across sites but all-titre serological syphilis was more prevalent among older participants in Rakai and Masaka than Mwanza. CONCLUSIONS: Differences between trial populations included higher reported risk behaviour and higher rates of curable STD in Mwanza compared to Rakai and Masaka. These differences probably relate to previous reductions in risk behaviour in Uganda and may explain, at least in part, the contrasting results of these trials.