Translating global health research aims into action: the example of the ALPHA network.

There is increasing consensus on the importance of strengthening global health research to meet health and development goals. Three key global health research aims are to ensure that research (i) addresses priority health needs, (ii) contributes to policy development, and (iii) adds value to investments in developing countries through South-South collaboration and capacity-strengthening in the South. The ALPHA network (Analysing Longitudinal Population-based HIV/AIDS data on Africa) is an illustrative example of how these global health research aims can be translated into action. The network facilitates additional collaborative HIV epidemiological research among six independent research projects in Africa studying population-based cohorts. Under the first of the earlier mentioned aims, the network addresses key epidemiology research issues in HIV/AIDS which are crucial to making progress and monitoring progress in the response against HIV/AIDS. Under the second aim, the network's scientific programme of research has contributed to strengthening the evidence base on HIV epidemiology in Africa and has informed policy development in areas such as targeted HIV prevention, social support, monitoring epidemic response and epidemic forecasting. Under the third aim, investment in the network has added value to the research investment in the individual projects through capacity development among African researchers as well as through the collaborative research outputs of the individual projects. Lessons from the network are relevant to collaborations facing similar challenges in other areas of global health research. These include the importance of establishing transparent and efficient governance for research collaborations, developing advance consensus on data sharing, ensuring effective communication for networking and demonstrating the added value of research investment in South-South collaborations.

Trends in age at first sex in Uganda: evidence from Demographic and Health Survey data and longitudinal cohorts in Masaka and Rakai.

OBJECTIVES: To derive the best possible estimates of trends in age at first sex (AFS) among successive cohorts of Ugandan men and women based on all the data available from the Demographic and Health Surveys (DHS) and cohort studies in Masaka and Rakai districts. METHODS: The datasets from the DHS, Masaka cohort and Rakai cohort were analysed separately. Survival analysis methods were used to estimate median AFS for men and women born in the 1950s-1980s and to compute hazard ratios for first sex, comparing later cohorts with earlier cohorts. RESULTS: The DHS and Masaka data showed an increase in AFS in women in the more recent birth cohorts compared with those born before 1970, but this was less apparent in the Rakai data. Successive male cohorts in Masaka appeared first to have an increased AFS which subsequently decreased, a trend that was also apparent (but not significant) in the DHS data. Younger men in Rakai had an earlier AFS than those born before 1980. CONCLUSIONS: Women in Uganda who were born after 1970 have, on average, had sex at a later age than those born earlier. For men, AFS has not changed consistently over the period in question. Differences between Masaka and Rakai may reflect socioeconomic differences. Most of the change in AFS occurred too late to have contributed to the initial decline in the incidence of HIV.

Trends in marriage and time spent single in sub-Saharan Africa: a comparative analysis of six population-based cohort studies and nine Demographic and Health Surveys.

OBJECTIVES: To describe trends in age at first sex (AFS), age at first marriage (AFM) and time spent single between events and to compare age-specific trends in marital status in six cohort studies. METHODS: Cohort data from Uganda, Tanzania, South Africa, Zimbabwe and Malawi and Demographic and Health Survey (DHS) data from Uganda, Tanzania and Zimbabwe were analysed. Life table methods were used to calculate median AFS, AFM and time spent single. In each study, two surveys were chosen to compare marital status by age and identify changes over time. RESULTS: Median AFM was much higher in South Africa than in the other sites. Between the other populations there were considerable differences in median AFS and AFM (AFS 17-19 years for men and 16-19 years for women, AFM 21-24 years and 18-19 years, respectively, for the 1970-9 birth cohort). In all surveys, men reported a longer time spent single than women (median 4-7 years for men and 0-2 years for women). Median years spent single for women has increased, apart from in Manicaland. For men in Rakai it has decreased slightly over time but increased in Kisesa and Masaka. The DHS data showed similar trends to those in the cohort data. The age-specific proportion of married individuals has changed little over time. CONCLUSIONS: Median AFS, AFM and time spent single vary considerably among these populations. These three measures are underlying determinants of sexual risk and HIV infection, and they may partially explain the variation in HIV prevalence levels between these populations.

Reported number of sexual partners: comparison of data from four African longitudinal studies.

OBJECTIVE: To compare reported numbers of sexual partners in Eastern and Southern Africa. METHODS: Sexual partnership data from four longitudinal population-based surveys (1998-2007) in Zimbabwe, Uganda and South Africa were aggregated and overall proportions reporting more than one lifetime sexual partner calculated. A lexis-style table was used to illustrate the average lifetime sexual partners by site, sex, age group and birth cohort. The male-to-female ratio of mean number of partnerships in the last 12 months was calculated by site and survey. For each single year of age, the proportion sexually active in the past year, the mean number of partners in the past year and the proportion with more than one partner in the past year were calculated. RESULTS: Over 90% of men and women between 25 and 45 years of age reported being sexually active during the past 12 months, with most reporting at least one sexual partner. Overall, men reported higher numbers of lifetime sexual partners and partners in the last year than women. The male-to-female ratio of mean partnerships in the last year ranged from 1.41 to 1.86. In southern African cohorts, individuals in later birth cohorts reported fewer sexual partners and a lower proportion reported multiple partnerships compared with earlier birth cohorts, whereas these behavioural changes were not observed in the Ugandan cohorts. Across the four sites, reports of sexual partnerships followed a similar pattern for each sex. CONCLUSIONS: The longitudinal results show that reductions in the number of partnerships were more evident in southern Africa than in Uganda.

Burden of infection among heads and non-head of rural households in Rakai, Uganda.

The objective was to determine HIV prevalence, symptomatology and mortality among adult heads and non-heads of households, in order to assess the burden of HIV on households. It was a community study of 11,536 adults aged 15-59, residing in 4,962 households in 56 villages, Rakai district, Uganda. First, 4,962 heads and 6,574 non-heads of households were identified from censuses. Interviews were then used to determine socio-demographic/behavioural characteristics. HIV seroprevalence was diagnosed by two EIAs with Western blot confirmation. The adjusted odds ratio (OR) and 95% confidence intervals (CI) of HIV infection in household heads and non-heads were estimated by multivariate logistic regression. Age-adjusted mortality was also assessed. HIV prevalence was 16.9% in the population, and 21.5% of households had at least one HIV-infected person (<0.0001). HIV prevalence was higher among heads than non-heads of households (21.5 and 13.3%, respectively, OR=1.79; CI 1.62-1.97). Most household heads were males (70.5%), and HIV prevalence was 17.8% among male heads compared with 6.6% in male non-heads of households (OR=2.31; CI 1.65-2.52). Women heading households were predominantly widowed, separated or divorced (64.4%). HIV prevalence was 30.5% among female heads, compared with 15.6% in female non-household heads (OR=1.42; CI 1.15-1.63). Age-adjusted mortality was significantly lower among male household heads than non-heads, both for the HIV-positive (RR=0.68) and HIV-negative men (RR=0.63). Among women, HIV-negative female household heads had significantly higher mortality than HIV-uninfected female non-heads (RR=1.72). HIV disproportionately affects heads of households, particularly males. Mortality due to AIDS is likely to increase the proportion of female-headed households, and adversely affect the welfare of domestic units.

Population-based HIV testing and counseling in rural Uganda: participation and risk characteristics.

OBJECTIVES: To assess self-selection in a population-based voluntary HIV testing and counseling (VTC) program by comparing the HIV risk characteristics of users and nonusers of VTC in rural Uganda. DESIGN: A 1994 to 1995 community-randomized trial in the Rakai District of Uganda enrolled adults aged 15 to 59 years and ascertained their HIV status, sociodemographic characteristics, risk behaviors, and AIDS-associated symptoms. All subjects were offered confidential individual VTC at no cost. METHODS: We compared users and nonusers of VTC among 10,950 participants (4764 male and 6186 female) enrolled at baseline using multivariate logistic regression. RESULTS: Women were significantly less likely to receive VTC than men (31.5% vs. 34.8%, p <.001). In multivariate analysis, younger age, HIV-positive status, and having no sexual partners in the past 5 years (and, significant for women only, having 2 or more sexual partners) were associated with lower VTC participation for both men and women. Among women, higher VTC participation was associated with symptoms suggestive of AIDS and other illnesses and shopkeeper occupations. CONCLUSIONS: During the initial phase of a population-based free VTC program in rural Uganda, certain high-risk groups were underrepresented among VTC recipients. There is a need to target VTC to ensure participation by high-risk individuals most in need of services.

HIV incidence and sexually transmitted disease prevalence associated with condom use: a population study in Rakai, Uganda.

OBJECTIVE: Evidence of condom effectiveness for HIV and sexually transmitted disease (STD) prevention is based primarily on high-risk populations. We examined condom effectiveness in a general population with high HIV prevalence in rural Africa. METHODS: Data were from a randomized community trial in Rakai, Uganda. Condom usage information was obtained prospectively from 17,264 sexually active individuals aged 15-59 years over a period of 30 months. HIV incidence and STD prevalence was determined for consistent and irregular condom users, compared to non-users. Adjusted rate ratios (RR) of HIV acquisition were estimated by Poisson multivariate regression, and odds ratios of STDs estimated by logistic regression. RESULTS: Only 4.4% reported consistent condom use and 16.5% reported inconsistent use during the prior year. Condom use was higher among males, and younger, unmarried and better educated individuals, and those reporting multiple sex partners or extramarital relationships. Consistent condom use significantly reduced HIV incidence [RR, 0.37; 95% confidence interval (CI), 0.15-0.88], syphilis [odds ratio (OR), 0.71; 95% CI, 0.53-0.94] and gonorrhea/Chlamydia (OR, 0.50; 95% CI, 0.25-0.97) after adjustment for socio-demographic and behavioral characteristics. Irregular condom use was not protective against HIV or STD and was associated with increased gonorrhea/Chlamydia risk (OR, 1.44; 95% CI, 1.06-1.99). The population attributable fraction of consistent use for prevention of HIV was -4.5% (95% CI, -8.3 to 0.0), due to the low prevalence of consistent use in the population. CONCLUSIONS: Consistent condom use provides protection from HIV and STDs, whereas inconsistent use is not protective. Programs must emphasize consistent condom use for HIV and STD prevention.

Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.

BACKGROUND: The probability of HIV-1 transmission per coital act in representative African populations is unknown. We aimed to calculate this probability overall, and to estimate how it is affected by various factors thought to influence infectivity. METHODS: 174 monogamous couples, in which one partner was HIV-1 positive, were retrospectively identified from a population cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting within couples was assessed prospectively. HIV-1 seroconversion was determined in the uninfected partners, and HIV-1 viral load was measured in the infected partners. Adjusted rate ratios of transmission per coital act were estimated by Poisson regression. Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load, and for symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1-infected partners. RESULTS: The mean frequency of intercourse was 8.9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 (95% CI 0.0008-0.0015). Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more (p=0.002), and were 0.0041 with genital ulceration versus 0.0011 without (p=0.02). Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner. INTERPRETATION: Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population.

Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. Rakai Project Team.

BACKGROUND: Male circumcision is associated with reduced HIV acquisition. METHODS: HIV acquisition was determined in a cohort of 5507 HIV-negative Ugandan men, and in 187 HIV-negative men in discordant relationships. Transmission was determined in 223 HIV-positive men with HIV-negative partners. HIV incidence per 100 person years (py) and adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated by Poisson regression. HIV-1 serum viral load was determined for the seropositive partners in HIV-discordant couples. RESULTS: The prevalence of circumcision was 16.5% for all men; 99.1% in Muslims and 3.7% in non-Muslims. Circumcision was significantly associated with reduced HIV acquisition in the cohort as a whole (RR 0.53, CI 0.33-0.87), but not among non-Muslim men. Prepubertal circumcision significantly reduced HIV acquisition (RR 0.49, CI 0.26-0.82), but postpubertal circumcision did not. In discordant couples with HIV-negative men, no serconversions occurred in 50 circumcised men, whereas HIV acquisition was 16.7 per 100 py in uncircumcised men (P = 0.004). In couples with HIV-positive men, HIV transmission was significantly reduced in circumcised men with HIV viral loads less than 50000 copies/ml (P = 0.02). INTERPRETATION: Prepubertal circumcision may reduce male HIV acquisition in a general population, but the protective effects are confounded by cultural and behavioral factors in Muslims. In discordant couples, circumcision reduces HIV acquisition and transmission. The assessment of circumcision for HIV prevention is complex and requires randomized trials.

Mortality associated with HIV infection in rural Rakai District, Uganda.

OBJECTIVE: To assess mortality impact of HIV in rural Uganda. METHODS: An open cohort of 19983 adults aged 15-59 years, in Rakai district was followed at 10 month intervals for four surveys. Sociodemographic characteristics and symptomatology/disease conditions were assessed by interview. Deaths among residents and out-migrants were identified household census. Mortality rates were computed per 1000 person years (py) and the rate ratio (RR) of death in HIV-positive/HIV-negative subjects, and the population attributable fraction (PAF) of death were estimated according to sociodemographic characteristics. Mortality associated with potential AIDS defining symptoms and signs was assessed. RESULTS: HIV prevalence was 16.1%. Mortality was 132.6 per 1000 py in HIV-infected versus 6.7 per 1000 py in uninfected subjects, and 73.5% of adult deaths were attributable to HIV infection. Mortality increased with age, but the highest attributable risk of HIV associated deaths were observed in persons aged 20-39 years (PAF > 80%) and in women. HIV associated mortality was highest in the better educated (PAF > or = 75%) and among government employees (PAF > or = 82%). Of the HIV-positive subjects 40.5% reported no illness < 10 months preceding death, symptoms were poor predictors of death (sensitivity 1.6-38.8%), and only 9.1% met the World Health Organization clinical definition of AIDS. Infant mortality rates in babies of HIV-infected and uninfected mothers were 209.4 and 97.7 per 1000, respectively. CONCLUSION: HIV is taking substantial toll in this population, particularly among the younger better educated adults, and infants. Symptomatology or the World Health Organization definition of AIDS are poor predictors of death.

Trends and determinants of contraceptive use in Rakai District, Uganda, 1995-98.

A prospective study conducted between 1995 and 1998 assessed trends in contraceptive use in rural Rakai District, Uganda. Over a period of 30 months, women's use of modern contraceptives increased significantly from 11 percent to 20 percent. Male condom use increased from 10 percent to 17 percent. The prevalence of pregnancy among sexually active women 15-49 declined significantly from 15 percent to 13 percent. Women practicing family planning for pregnancy prevention were predominantly in the 20-39-year age group, married, better educated, and had higher parity than others, whereas women or men adopting condoms were predominantly young, unmarried, and better educated. Condom use was particularly high among individuals reporting multiple sexual partners or extramarital relationships. Contraceptive use was higher among women who desired fewer children, among those who wished to space or terminate childbearing, and among women with previous experience of unwanted births or abortions. Self-perception of HIV risk increased condom use, but HIV testing and counseling had only modest effects. Contraception for pregnancy prevention and for HIV/STD prophylaxis are complementary.

Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group.

BACKGROUND AND METHODS: We examined the influence of viral load in relation to other risk factors for the heterosexual transmission of human immunodeficiency virus type 1 (HIV-1). In a community-based study of 15,127 persons in a rural district of Uganda, we identified 415 couples in which one partner was HIV-1-positive and one was initially HIV-1-negative and followed them prospectively for up to 30 months. The incidence of HIV-1 infection per 100 person-years among the initially seronegative partners was examined in relation to behavioral and biologic variables. RESULTS: The male partner was HIV-1-positive in 228 couples, and the female partner was HIV-1-positive in 187 couples. Ninety of the 415 initially HIV-1-negative partners seroconverted (incidence, 11.8 per 100 person-years). The rate of male-to-female transmission was not significantly different from the rate of female-to-male transmission (12.0 per 100 person-years vs. 11.6 per 100 person-years). The incidence of seroconversion was highest among the partners who were 15 to 19 years of age (15.3 per 100 person-years). The incidence was 16.7 per 100 person-years among 137 uncircumcised male partners, whereas there were no seroconversions among the 50 circumcised male partners (P<0.001). The mean serum HIV-1 RNA level was significantly higher among HIV-1-positive subjects whose partners seroconverted than among those whose partners did not seroconvert (90,254 copies per milliliter vs. 38,029 copies per milliliter, P=0.01). There were no instances of transmission among the 51 subjects with serum HIV-1 RNA levels of less than 1500 copies per milliliter; there was a significant dose-response relation of increased transmission with increasing viral load. In multivariate analyses of log-transformed HIV-1 RNA levels, each log increment in the viral load was associated with a rate ratio of 2.45 for seroconversion (95 percent confidence interval, 1.85 to 3.26). CONCLUSIONS: The viral load is the chief predictor of the risk of heterosexual transmission of HIV-1, and transmission is rare among persons with levels of less than 1500 copies of HIV-1 RNA per milliliter.

Relative risks and population attributable fraction of incident HIV associated with symptoms of sexually transmitted diseases and treatable symptomatic sexually transmitted diseases in Rakai District, Uganda. Rakai Project Team.

OBJECTIVES: To assess the linkage of sexually transmitted disease (STD) symptoms and treatable STD to HIV incidence. DESIGN: Analysis of a randomized trial of STD control for HIV prevention, Rakai, Uganda. METHODS: Consenting adults 15-59 years of age were seen at 10-monthly home visits, interviewed regarding STD symptoms, and asked to provide samples for HIV and STD diagnoses. HIV incidence was determined in 8089 HIV-negative subjects over 10 457 person years. Adjusted rate ratios (RR) and 95% confidence intervals (CI) of HIV acquisition associated with genital ulcer disease (GUD) and discharge/dysuria were used to estimate the population attributable fraction (PAF) of HIV acquisition. HIV transmission risks associated with STD symptoms in HIV-positive partners of 167 HIV discordant couples and the numbers of sexual partners reported by HIV-positive subjects were used to estimate the PAF of HIV transmission attributable to STD. RESULTS: HIV prevalence was 16%. The risk of HIV acquisition was increased with GUD (RR 3.14; CI 1.98-4.98) and in males with discharge/dysuria (RR 2.44; CI 1.17-5.12), but not in females with discharge/dysuria. The PAF of HIV acquisition was 9.5% (CI 2.8-15.8%) with any of the three STD symptoms. The PAF for GUD was 8.8% (CI 3.7-13.8), but only 8.2% of reported GUD was caused by treatable syphilis or chancroid . The PAF for discharge/dysuria in males was 6.7% (CI 1.1-13.8), but only 25% of symptomatic males had concurrent gonorrhea or chlamydial infection. No significant differences were seen in PAF between study treatment arms. The PAF of HIV transmission associated with STD symptoms in HIV-positive persons was indirectly estimated to be 10.4%. CONCLUSION: In this mature, generalized HIV epidemic setting, most HIV seroconversion occurs without recognized STD symptoms or curable STD detected by screening. Therefore, syndromic management or other strategies of STD treatment are unlikely to substantially reduce HIV incidence in this population. However, STD is associated with significant HIV risk at the individual level, and STD management is needed to protect individuals.

Sensitivity and specificity of HIV-1 testing of urine compared with serum specimens: Rakai, Uganda. The Rakai Project Team.

BACKGROUND AND OBJECTIVES: To evaluate a urine HIV-1 test. STUDY DESIGN: Paired urine and blood samples from a sample of 222 subjects were assayed for HIV-1 using Calypte HIV-1 Urine enzyme immunoassay (EIA) with Western blot (WB) confirmation, and sera were tested by EIA and WB. Masked assays were done on stored, refrigerated urine at Johns Hopkins University (JH), and on fresh specimens at the Rakai Project, Entebbe (RP). We assessed the sensitivity and specificity of the urine relative to serum assays. RESULTS: Compliance with provision of urine samples (95.0%) was higher than provision of serum (90.5%). Ninety-six sera were HIV-positive; 92 were HIV-positive on stored urine at JH (sensitivity 95.8%, CI 91.8-99.8%); and 94 (100%) were positive on fresh samples at the RP laboratory (sensitivity = 100.0%). Among serum HIV-negative subjects, all frozen urine were negative at JH and 97.7% of fresh samples were negative at RP. CONCLUSIONS: The Calypte urine HIV-1 EIA with WB is sensitive and specific. In this population, provision of urine was more acceptable than provision of blood samples.

Education attainment as a predictor of HIV risk in rural Uganda: results from a population-based study.

We examined the association between education and prevalent HIV-1 infection in the Rakai district, rural Uganda based on a cross-sectional analysis of a population-based cohort. In 1990, 1397 men and 1705 women aged 13 years and older, were enrolled in 31 randomly selected communities. Strata were comprised of main road trading centres, secondary road trading villages and rural villages. Sociodemographic and behavioural data were obtained by interview and serum for HIV serostatus were obtained in the home. The analysis examines the association between sex-specific prevalent HIV infection and educational attainment, categorized as secondary, primary or none. The odds ratios (ORs) and 95% confidence intervals (95% CIs) of HIV infection were estimated, using no education as the referent group. Higher levels of education were associated with a higher HIV seroprevalence in bivariate analyses (OR 2.7 for primary and 4.1 for secondary education, relative to no education). The strength of the association was diminished but remained statistically significant after multivariate adjustment for sociodemographic and behavioural variables (adjusted OR of HIV infection 1.6 (95% CI: 1.2-2.1)) for primary education and 1.5 (95% CI: 1.0-2.2) for secondary education. Stratified multivariate analyses by place of residence indicated that the association between education and HIV prevalence was statistically significant in the rural villages, but not in the main road trading centres and intermediate trading villages. Educational attainment is a significant predictor of HIV risk in rural Uganda, in part because of risk behaviours and other characteristics among better educated individuals. Preventive interventions need to focus on better educated adults and on school-aged populations.

PIP: This is a cross-sectional analysis of a population-based cohort study conducted to examine both the associations between educational attainment and HIV-1 serostatus as well as the relationship between education and other HIV risk factors in Rakai district, Uganda. A total of 3102 respondents (1397 men and 1705 women aged 13 years and older) completed a questionnaire and provided blood samples. The samples of community clusters was stratified into three strata: trading centers on main roads, intermediate trading villages on secondary roads, and rural agricultural villages with no roads or only minor road connection. Analysis has shown a consistent association between higher level of educational attainment and HIV-1 prevalence among the residents. The strength of the association was decreased but remained statistically relevant after multivariate adjustment for sociodemographic and behavioral variables [adjusted OR for HIV infection, 1.6 (95% CI, 1.2-2.1) for primary education and 1.5 (95% CI, 1.0-2.2) for secondary education]. Stratified multivariate analyses by place of residence showed that the relationship between education and HIV prevalence was markedly higher in the rural villages compared to the other two strata. Education provides greater economic resources, which facilitate behaviors that put individuals at greater risk. Analysis of findings suggests that HIV prevention strategies should focus on the more educated individuals, particularly in rural settings and among younger women.

Age of male circumcision and risk of prevalent HIV infection in rural Uganda.

OBJECTIVE: To assess whether circumcision performed on postpubertal men affords the same level of protection from HIV-1 acquisition as circumcisions earlier in childhood. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rakai district, rural Uganda. METHODS: A total of 6821 men aged 15-59 years were surveyed and venous blood samples were tested for HIV-1 and syphilis. Age at circumcision was dichotomized into men who were circumcised before or at age 12 years (prepubertal) and men circumcised after age 12 years (postpubertal). Postpubertal circumcised men were also subdivided into those reporting circumcision at ages 13-20 years and > or = 21 years. RESULTS: HIV-1 prevalence was 14.1% in uncircumcised men, compared with 16.2% for men circumcised at age > or = 21 years, 10.0% for men circumcised at age 13-20 years, and 6.9% in men circumcised at age < or = 12 years. On bivariate analysis, lower prevalence of HIV-1 associated with prepubertal circumcision was observed in all age, education, ethnic and religious groups. Multivariate adjusted odds ratio of prevalent HIV-1 infection associated with prepubertal circumcision was 0.39 [95% confidence interval (CI), 0.29-0.53]. In the postpubertal group, the adjusted odds ratio for men circumcised at ages 13-20 years was 0.46 (95% CI, 0.28-0.77), and 0.78 (95% CI, 0.43-1.43) for men circumcised after age 20 years. CONCLUSIONS: Prepubertal circumcision is associated with reduced HIV risk, whereas circumcision after age 20 years is not significantly protective against HIV-1 infection. Age at circumcision and reasons for circumcision need to be considered in future studies of circumcision and HIV risk.

Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group.

BACKGROUND: The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities. METHODS: This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios. FINDINGS: The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses. INTERPRETATION: We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.

A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

PIP: An ongoing (1994-98) randomized, community-based trial in Uganda's Rakai District is assessing the assumption that intensive sexually transmitted disease (STD) control efforts result in marked declines in HIV/AIDS prevalence. Described, in this article, are the project design and findings of the first-round baseline survey. 56 communities were grouped into 10 clusters designed to encompass social/sexual networks and clusters within blocks were randomly assigned to the intervention or control arm. All consenting permanent residents of the district are visited in their homes at 10-month intervals where they are administered extensive questionnaires, provide urine and vaginal swab samples, and are offered mass treatment regardless of symptoms or laboratory testing (single oral dose STD treatment in the intervention arm and anthelmintics and iron folate in the control arm). Both groups receive identical health education, condom promotion, and serologic counseling services. In the first round of home visits, 5834 intervention and 5784 control arm subjects were enrolled, representing about 90% of eligible adults. The groups were comparable in terms of sociodemographic and behavioral characteristics and baseline rates of HIV and STDs. 16.9% of subjects were HIV-positive, 10.0% had syphilis, 23.8% of women had trichomonas, and 50.9% had bacterial vaginosis. Detailed STD assessment is expected not only to document the relationship between STD control and HIV, but also to identify which STDs confer the greatest population attributable risk for HIV transmission, facilitating targeted control efforts in the future.

Trends in HIV-1 prevalence may not reflect trends in incidence in mature epidemics: data from the Rakai population-based cohort, Uganda.

OBJECTIVES: To assess whether trends in serial HIV-1 prevalence reflect trend in HIV incidence, and to decompose the effects of HIV-1 incidence, mortality, mobility and compliance on HIV-1 prevalence in a population-based cohort. DESIGN: Two-year follow up (1990-1992) of an open cohort of all adults aged 15-59 years, resident in a sample of 31 representative community clusters in rural Rakai District, Uganda. METHODS: A detailed household enumeration was concluded at baseline and in each subsequent year. All household residents were listed, and all deaths and in- and out-migrations that occurred in the intersurvey year wee recorded. In each year, all consenting adults were interviewed and provided a serological sample; 2591 adults aged 15-59 years were enrolled at baseline. RESULTS: HIV prevalence among adults declined significantly 1990 and 1992 (23.4% at baseline, 21.8% in 1991, 20.9% in 1992; P < 0.05). Declining prevalence was also observed in subgroups, including young adults aged 15-24 years (from 20.6 to 16.2% over 3 years; P < 0.02), women of reproductive age (from 27.1 to 23.5%; P < 0.05), and pregnant women (from 25.4 to 20.0%; not significant), However, HIV incidence did not change significantly among all adults aged 15-59 years (2.1 +/- 0.4 per 100 person-years of observation (PYO) in 1990-1991 and 2.0 +/- 0.3 per 100 PYO in 1991-1992], nor in population subgroups. HIV-related mortality was high (13.5 per 100 PYO among the HIV-positive), removing more infected persons that were added by seroconversion. Net out-migration also removed substantial numbers of HIV-positive individuals. CONCLUSIONS: In this mature HIV epidemic, HIV prevalence declined in the presence of stable and incidence. HIV-related mortality contributed most to the prevalence decline. Prevalence was not an adequate surrogate measure of incidence, limiting the utility or serial prevalence measures in assessing the dynamics of the HIV epidemic and in evaluating the impact of current preventive strategies.

PIP: Findings are reported from a 2-year follow-up study of an open cohort of people aged 15-59 years living in a sample of 31 representative community clusters in rural Rakai district, Uganda, to measure whether trends in serial HIV-1 prevalence reflect trends in HIV incidence, and to gain insight into the effects of HIV-1 incidence, mortality, mobility, and compliance upon HIV-1 prevalence. In each year of study, all consenting adults provided a serological sample and were interviewed; 2591 adults were enrolled at baseline. HIV prevalence among adults declined significantly between 1990 and 1992; from 23.4% in 1990, to 21.8% in 1991, and 20.9% in 1992. Declining prevalence was also observed in subgroups, including young adults aged 15-24 years from 20.6% to 16.2%, reproductive-age women from 27.1% to 23.5%, and pregnant women from 25.4% to 20.0%. The decline in HIV prevalence among pregnant women, however, is not significant. HIV incidence did not change significantly among all adults aged 15-59 years, nor in population subgroups. HIV-related mortality was 13.5/person-year of observation among those who were HIV-positive. Substantial numbers of HIV-infected individuals were also loss to emigration.

A pilot study of antituberculosis combinations comparing rifabutin with rifampicin in the treatment of HIV-1 associated tuberculosis. A single-blind randomized evaluation in Ugandan patients with HIV-1 infection and pulmonary tuberculosis.

SETTING: This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, where tuberculosis (TB) is an epidemic health problem aggravated by the HIV-1 pandemic. OBJECTIVE: To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB. DESIGN: Single-blind randomized trial in 50 patients with new onset smear- and culture-positive pulmonary tuberculosis and HIV-1 infection. Comparison of daily, intermittently supervised 6-month treatment regimens of rifabutin versus rifampicin, together with isoniazid, ethambutol and pyrazinamide. RESULTS: Rifabutin- and rifampicin-containing regimens had comparable efficiency. However, rifabutin-treated patients had significantly more rapid clearance of acid-fast bacilli from sputum at 2 months (P < 0.05, Fisher exact test) and over the entire study period (P < 0.05, logrank test) than rifampicin-treated patients. The presence of cavitary disease was associated with a longer sputum conversion time for patients treated with either regimen. No major adverse events requiring dosage reduction or withdrawal of any study medication were seen in either treatment group. Mean absolute peripheral blood CD4 T lymphocyte counts increased by 28% from week 0 to week 12 in all subjects (334-427/microliters, respectively). An unexpected finding was the isolation of Mycobacterium africanum from 49% of the sputum cultures. This is the first report indicating a high prevalence of M. africanum in human TB in Uganda. CONCLUSION: Short-course antituberculosis regimens containing rifabutin or rifampicin are both safe and efficacious in the treatment of HIV-1 associated tuberculosis. Rifabutin-containing regimens were associated with earlier sputum smear and culture conversion.