HIV incidence among non-migrating persons following a household migration event: a population-based, longitudinal study in Uganda.

Background: The impact of migration on HIV risk among non-migrating household members is poorly understood. We measured HIV incidence among non-migrants living in households with and without migrants in Uganda. Methods: We used four survey rounds of data collected from July 2011-May 2018 from non-migrant participants aged 15-49 years in the Rakai Community Cohort Study, an open, population-based cohort. Non-migrants were individuals with no evidence of migration between surveys or at the prior survey. The primary exposure, household migration, was assessed using census data and defined as ≥1 household member migrating in or out of the house from another community between surveys (∼18 months). Incident HIV cases tested positive following a negative result at the preceding visit. Incidence rate ratios (IRR) with 95% confidence intervals were estimated using Poisson regression with generalized estimating equations and robust standard errors. Analyses were stratified by gender, migration into or out of the household, and the relationship between non-migrants and migrants (i.e., any household migration, spouse, child). Findings: Overall, 11,318 non-migrants (5,674 women) were followed for 37,320 person-years. 28% (6,059/21,370) of non-migrant person-visits had recent migration into or out of the household, and 240 HIV incident cases were identified in non-migrating household members. Overall, non-migrants in migrant households were not at greater risk of acquiring HIV. However, HIV incidence among men was significantly higher when the spouse had recently migrated in (adjIRR:2·12;95%CI:1·05-4·27) or out (adjIRR:4·01;95%CI:2·16-7·44) compared to men with no spousal migration. Women with in- and out-migrant spouses also had higher HIV incidence, but results were not statistically significant. Interpretation: HIV incidence is higher among non-migrating persons with migrant spouses, especially men. Targeted HIV testing and prevention interventions such as pre-exposure prophylaxis could be considered for those with migrant spouses. Funding: National Institutes of Health, US Centers for Disease Control and Prevention. Research in context: We searched PubMed for studies focused on HIV acquisition, prevalence or sexual behaviors among non-migrants who lived with migrants in sub-Saharan Africa (SSA) using search terms such as "HIV", "Emigration and Immigration", "family", "spouses", "household", "parents", and "children". Despite high levels of migration and an established association with HIV risk in SSA, there is limited data on the broader societal impacts of migration on HIV acquisition risk among non-migrant populations directly impacted by it.There has been only one published study that has previously evaluated impact of migration on HIV incidence among non-migrating persons in sub-Saharan Africa. This study, which exclusively assessed spousal migration, was conducted in Tanzania more than two decades earlier prior to HIV treatment availability and found that non-migrant men with long-term mobile partners were more than four times as likely to acquire HIV compared to men who had partners that were residents. To the best of our knowledge, this is the first study to examine the effect of non-spousal migration, including any household migration and child migration, on HIV incidence among non-migrants. Added value of this study: In this study, we used data from the Rakai Community Cohort Study (RCCS), a population-based HIV surveillance cohort to measure the impact of migration on HIV incidence for non-migrant household members. The RCCS captures HIV incident events through regular, repeat HIV testing of participants and migration events through household censuses. Our study adds to the current literature by examining the general effect of migration in the household on HIV incidence in addition to child, and spousal migration. Using data from over 11,000 non-migrant individuals, we found that spousal, but not other types of household migration, substantially increased HIV risk among non-migrants, especially among men. Taken together, our results suggest that spousal migration may be associated with an increased risk of HIV acquisition in the period surrounding and immediately after spousal migration. Implications of all the available evidence: Our findings suggest that spousal migration in or out of the household is associated with greater HIV incidence. Targeted HIV testing and prevention interventions such as pre-exposure prophylaxis could be considered for men with migrant spouses.

Evaluation of multiplex real-time PCR for detection of Haemophilus ducreyi, Treponema pallidum, herpes simplex virus type 1 and 2 in the diagnosis of genital ulcer disease in the Rakai District, Uganda.

OBJECTIVE: To develop a real-time PCR assay that reliably and accurately detects the predominant sexually transmitted aetiological agents of genital ulcer disease (GUD) (Haemophilus ducreyi, Treponema pallidum and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)) and to assess the use of real-time PCR diagnostic testing in a rural African field site. METHODS: Two multiplex real-time PCR reactions were used to detect H ducreyi/and HSV-1/HSV-2 in ulcer swabs from 100 people with symptomatic genital ulcers in rural Rakai, Uganda. Results were compared with syphilis, HSV-1 and HSV-2 serology. RESULTS: Of 100 GUD samples analysed from 43 HIV positive and 57 HIV negative individuals, 71% were positive for one or more sexually transmitted infection (STI) pathogens by real-time PCR (61% for HSV-2, 5% for T pallidum, 3% for HSV-1, 1% for H ducreyi and 1% for dual H ducreyi/HSV-2). The frequency of HSV in genital ulcers was 56% (32/57) in HIV negative individuals and 77% (33/43) in HIV positive individuals (p = 0.037). Assay reproducibility was evaluated by repeat PCR testing in the USA with 96% agreement (kappa = 0.85). CONCLUSIONS: STI pathogens were detected in the majority of GUD swab samples from symptomatic patients in Rakai, Uganda, by real-time PCR. HSV-2 was the predominant cause of genital ulcers. Real-time PCR technology can provide sensitive, rapid and reproducible evaluation of GUD aetiology in a resource-limited setting.

Prevalence and risk factors for carcinogenic human papillomavirus infections in rural Rakai, Uganda.

OBJECTIVE: To investigate self-administered vaginal swabs for assessing prevalence and correlates of carcinogenic human papillomavirus (HPV) infection in rural Rakai, Uganda. METHODS: 1003 sexually experienced women enrolled in a community cohort provided self-administered vaginal swabs collected at annual, home-based surveys. Carcinogenic HPV prevalence, adjusted odds ratios (AOR), 95% confidence intervals (CI) and associated risk factors were determined. RESULTS: Carcinogenic HPV prevalence was 19.2%: 46.6% among HIV positive and 14.8% among HIV negative women (p<0.001). Type-specific prevalence ranged from 2.0% (HPV 16 and 52) to 0.2% (HPV 31). Age-specific HPV prevalence decreased significantly (p<0.001) among HIV negative women; however, the decrease among HIV positive women was not as pronounced (p = 0.1). Factors independently associated with carcinogenic HPV infection were HIV (AOR 4.82, CI 3.10 to 7.53), age (AOR 4.97, 95% CI 2.19 to 11.26 for 15-19 year olds compared to 40+ years), more than two sex partners in the past year (AOR 2.21, CI 1.10 to 4.43) and self-reported herpes zoster, candidiasis or tuberculosis (AOR 4.52, CI 1.01 to 20.31). Married women were less likely to have prevalent carcinogenic HPV (AOR 0.46, CI 0.30 to 0.70). CONCLUSIONS: HPV prevalence and correlates measured using self-administered vaginal swabs were similar to studies that use cervical samples. Thus, self-collection can be used as a substitute for cervical specimens and provide an important tool for research in populations unwilling to undergo pelvic exam.

HIV risk factors in three geographic strata of rural Rakai District, Uganda.

OBJECTIVES: To examine risk factors for HIV-1 infection in three geographic strata (main road trading centers that service local and international traffic, small trading villages on secondary dirt roads that serve as foci for local communications, and agricultural villages off main and secondary roads) in Rakai District, Uganda. DESIGN AND METHODS: Serological, sociodemographic, knowledge/behaviors and health survey conducted in 21 randomly selected community clusters; complete data were collected for 1292 consenting adults. RESULTS: Fifteen per cent of the men and 24% of the women were HIV-1-positive. On univariate analysis, several sociodemographic and behavioral factors were significantly associated with risk of HIV infection, including age, place of residence, travel, occupation, marital status, number of sex partners, sex for money or gifts, history of sexually transmitted disease (STD), and history of injections. On multivariate analysis, age, residence and number of sex partners remained significantly associated with HIV infection in both sexes; a history of STD and not having been circumcised were significant in men. There was a significant interaction between place of residence and reported number of sex partners: for any given level of sexual activity, the risk of HIV infection was markedly increased if the background community prevalence was high. CONCLUSION: Sexual transmission appears to be the primary behavioral risk factor for infection, but the risks associated with this factor vary substantially between the three geographic strata. These data can be used to design targeted interventions.

The social dynamics of HIV transmission as reflected through discordant couples in rural Uganda.

OBJECTIVE: To describe the role of men and women as sources of HIV transmission and to estimate HIV incidence among discordant couples resident in diverse rural communities in Uganda. SETTING: Rakai, a rural district in Uganda, East Africa. METHODS: A population-based cohort study, which has been conducted as annual serological and behavioral surveys since 1989. Community clusters were stratified into trading centers on main roads, intermediate trading villages on secondary roads and agricultural villages off roads. In the 1990 survey round, serological data were available for 79 discordant and 411 concordant HIV-negative couples aged 13-49 years. The present analysis examines sex-specific seropositivity associated with place of residence and the incidence of seroconversion among discordant couples between 1990 and 1991. RESULTS: Seventy-nine discordant couples were followed; the HIV-positive partner was male in 44 couples (57%) and female in 35 couples (43%). There was marked variation in the sex of the seropositive partner by place of residence: women were the HIV-positive partner in 57% of couples from trading centers, 52% from intermediate villages, and 20% from agricultural communities (P < 0.008). Condom use was higher in discordant couples in which the man was the uninfected partner (17.1%) rather than the woman (9.5%). HIV-positive women, but not HIV-positive men, reported significantly more sexual partners and more genital ulcers than seronegative individuals of the same sex. Seroincidence rates among men and women in discordant relationship were 8.7 and 9.2 per 100 person-years (PY), respectively, which was much higher than in concordant seronegative couples (men, 0.82; women, 0.87 per 100 PY). CONCLUSIONS: In this Ugandan population, men are the predominant source of new infections in rural villages. Risk factors and preventive behaviors vary with the sex of the infected partner, and seroconversion rates are similar in both sexes.

PIP: The analysis of marital relationships in rural Uganda in which one partner is infected with human immunodeficiency virus (HIV) revealed important information about the social dynamics of HIV transmission. As part of an ongoing cohort study of over 3000 adults in southwestern Uganda's Rakai district, data were collected on 79 discordant couples. The HIV-infected partner was male in 44 couples (57%) and female in 35 couples (43%). In the trading centers and intermediate trading villages, women were more likely to be the HIV-infected partner (57% and 52%, respectively); in rural areas, however, the male partner was the HIV carrier in 80% of discordant couples. 14.3% of women in female HIV-positive compared to only 2.1% of those in male HIV-positive discordant relationships reported two or more sexual partners in the year preceding the interview; there was no significant difference on this factor among HIV-positive and HIV-negative men (48.8% and 45,7%, respectively). 17.1% of seronegative men with HIV-infected wives compared to only 9.5% of seropositive men with seronegative wives used condoms with their partner. During the one-year study period, the rate of seroconversion was 8.7/100 years of observation for men and 9.2 for women. Extrapolation of the data from this study to the district as a whole suggests that 18.7% of couples have at least one HIV-infected member. Needed are campaigns to promote monogamy and condom use, particularly among men from rural areas who travel to high prevalence trading areas.

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.

Demographic impact of HIV infection in rural Rakai district, Uganda: results of a population-based cohort study.

OBJECTIVES: To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. DESIGN: One-year follow-up (1990-1991) in a population-based rural cohort. SETTING AND PARTICIPANTS: Annual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters in Rakai District. Subjects provided yearly HIV serological samples, behavioral and health information. MAIN OUTCOME MEASURE: Mortality in HIV-infected and uninfected persons. RESULTS: Mortality among HIV-seropositive adults aged > or = 15 years of 118.4 per 1000 person-years (PY) was substantially higher than in HIV-seronegative adults [12.4 per 1000 PY; relative risk (RR), 9.5; 95% confidence interval (CI), 6.0-14.9]. Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women (210 compared with 111 per 1000 live births; RR, 1.9; 95% CI, 1.0-3.5). Adult HIV-related mortality was associated with HIV prevalence and, in this cohort, with higher education, non-agricultural occupation and residence in roadside trading centers. We estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined, district HIV attributable mortality is 28%. CONCLUSION: HIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However, the overall crude birth rate in the district (45.7 per 1000 population) remains higher than the crude death rate (28.1 per 1000 population), resulting in continued rapid population growth.

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.

Adolescents, sexual behaviour and HIV-1 in rural Rakai district, Uganda.

OBJECTIVES: To describe the epidemiology of HIV-1 infection among adolescents aged 13-19 years, in rural Rakai district, Uganda. STUDY DESIGN: Baseline survey and 2-year follow-up (1990-1992) of adolescents in a population-based, open rural cohort. METHODS: Annual enumeration and behavioral/serological survey of all consenting adolescents aged 13-19 years at recruitment, residing in 31 randomly selected community clusters. RESULTS: At baseline, of 909 adolescents present in study clusters, 824 (90.6%) provided interview data and serological samples. No adolescents aged 13-14 years were HIV-infected. Among those aged 15-19 years, 1.8% of men and 19.0% of women were HIV-positive. Among young women aged 15-19 years in marital/consensual union, 21.3% were HIV-positive; this rate did not differ significantly from the 29.1% prevalence in those reporting non-permanent relationships; prevalence was significantly lower in women reporting no current relationship (4.3%). After multivariate adjustment, female sex, age 17-19 years, residence in trading centers/trading villages and a history of sexually transmitted disease symptoms remained significantly associated with HIV infection. Seventy-nine per cent of adolescents provided a follow-up serological sample. No young men aged 13-14 years seroconverted during the study; in young women aged 13-14 years, HIV seroincidence was 0.6 per 100 person-years (PY) of observation. Among young men aged 15-19 years, there were 1.1 +/- 0.6 seroconversions per 100 PY of observation prior to age 21 years; among women 15-19 years, the incidence rate was 3.9 +/- 1.0 per 100 PY of observation prior to age 21 years. The mortality rate among HIV-positive adolescents aged 15-19 years, at 3.9 per 100 PY of observation, was 13-fold higher than that among the HIV-uninfected. By 1992, knowledge of sexual transmission was almost universal, the proportions reporting multiple partners had decreased and condom use had increased over baseline. CONCLUSIONS: Adolescents, and young women in particular, are vulnerable to HIV infection. Despite reported behavioral changes, HIV incidence rates remain substantial, and there is a need for innovative HIV preventive measures.

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.

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.

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.

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.

Phylogenetic and serological characterization of two Ugandan HIV-1 isolates.

HIV-1 isolates Ug06 and Ug23 were established in culture from peripheral blood mononuclear cells (PBMCs) of Ugandan subjects. The isolates were studied for phylogenetic and serological relationships with each other and with the laboratory strains, HTLV-IIIB and HIV-1MN. The results suggest that the Ugandan isolates are related to different subgroups of African viruses with 17.3% of genetic distance between UG06 and the U455 provirus (Uganda); and 12.6% of genetic distance between UG23 and the JY1 provirus (Zaire). Analysis of the predicted amino acid sequences for Ug06 and Ug23 showed marked sequence heterogeneity in the V3 region and CD4-binding site. A conserved amino acid sequence was identified in the C-terminal immunodominant region of the envelope glycoprotein gp120. The isolates were compared in virus-neutralization experiments with HTLV-IIIB and HIV-1MN stocks, using panels of Western blot-positive North American and Ugandan sera. The North American serum samples showed broad neutralizing activity against both of the Ugandan isolates. However, the Ugandan serum panel demonstrated strain-specific activity against either Ug06 or Ug23. Furthermore, the African serum specimens showed higher prevalence and titers of neutralizing activity against the HIV-1MN stock as compared with HTLV-IIIB.

Nucleotide sequence of a Ugandan HIV-1 provirus reveals genetic diversity from other HIV-1 isolates.

A Ugandan isolate of human immunodeficiency virus type 1 (HIV-1), designated U455, was adapted to growth in U937 cells, the provirus cloned into the lambda L47.1 vector, and its DNA sequence determined. The sequences of some of the U455 genes showed a marked divergence from those of North American and other African isolates. The sequenced clone was defective with single in-phase stop codons in the vpr and env genes and frame shift, resulting in a stop codon, within the vpu gene.

Immunological effects of HIV-1 infection on the humoral response to malaria in an African population.

We conducted a cross-sectional study to determine the serological response to malaria in an HIV-1 infected population and in a control population in a region of high malaria transmission. The study group consisted of 66 hospitalized patients with clinical acquired immunodeficiency syndrome (AIDS) and 70 trauma patients without clinical AIDS (controls). Mean optical densities of antibody produced against RESA-4, RESA-8, RESA-11, (PNAN)5 and (NAAG)5 synthetic peptides of Plasmodium falciparum were compared between HIV-1 seropositive and HIV-1 seronegative patients using non-parametric statistics. HIV-1 seropositive patients with clinical AIDS had significantly less antibody to the synthetic P. falciparum ring stage peptide, RESA-8 (P = 0.001), than a comparable group of seronegative patients. Antibody levels were also low for the other ring stage peptides, RESA-4 (P = 0.024) and RESA-11 (P = 0.024). Although not statistically significant, antibody levels among the HIV-1 seropositive trauma patients were higher than among the HIV-1 seronegative trauma patients. During HIV-1 infection, a polyclonal B cell activation may occur as noted in the HIV-1 seropositive trauma patients, but with increased immunosuppression in advanced clinical AIDS, B cell stimulation appears to be diminished. This results in decreased production of malaria antibody.

Planning and evaluating strategies for AIDS health education interventions in the Muslim community in Uganda.

In 1992 the Islamic Medical Association of Uganda designed an AIDS prevention project. A baseline survey was conducted to assess prevailing knowledge, attitudes, and practices among the Muslim communities in two districts. A low rate of incorrect beliefs about HIV transmission was found, although gaps in knowledge remain, particularly regarding vertical transmission and asymptomatic HIV infection. Less than 10% knew that condoms can protect against HIV transmission. Lack of knowledge was documented regarding the risk of HIV transmission associated with practices common in the Islamic community, such as polygamous marriages, circumcision, and ablution of the dead. The AIDS prevention project has incorporated specific messages and interventions as a result of these findings.

PIP: The Islamic Medical Association of Uganda has designed a project known as Family Acquired Immunodeficiency Syndrome (AIDS) Education and Prevention Through Imams. In a 1992 baseline survey, 1096 persons from the pilot project's two target districts--Mpigi and Iganga--were interviewed. Respondents were recruited from mosques in both rural and trade center areas of the districts. The mass media was identified as the main source of information about AIDS by 49.6% of respondents in Iganga and 80% of those in the more urbane Mpigi district. Only 3% of respondents in both communities viewed the imam (mosque leader) as someone with whom they could discuss concerns about AIDS. Although 80% of respondents were aware that the main route of transmission of the AIDS virus is sexual, only 1.2% knew about the possibility of maternal-fetal transmission. 55.4% recognized a condom, but just 9.9% had ever used one. In this culture, condom use is associated with sexual promiscuity and is not used within marriage. The survey identified three risk factors prevalent among Uganda's Muslim minority: polygamous marriage, practiced by about a third of respondents; use of the same cutting instrument for multiple male circumcision procedures without sterilization in between; and ablution of the dead, without the use of protective gloves. These cultural practices will be targeted in the AIDS prevention campaign. In each district, 10 imams will receive intensive training in AIDS and community education skills. Each imam will be provided with a male and female assistant who, in turn, will train indigenous family workers selected by the mosque. These community workers will make monthly home visits to about 15 families in the mosque area.

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.

Human immunodeficiency virus and AIDS in Uganda.

HIV-1 infection, initially described as "slim disease", was first recognized in Uganda in 1982, and is now a predominant health problem. Approximately 1.5 million Ugandans are now infected, largely through heterosexual transmission. In many areas half of adult deaths are now caused by HIV. Seroprevalence rates in urban antenatal clinics have been dropping in the last several years, as have rates in young adults in two rural community cohorts where the epidemic is long established. Tuberculosis cases and admissions have increased dramatically. Among the clinical manifestations of HIV in Uganda, epidemic Kaposi sarcoma, cryptococcal meningitis, suspected toxoplasmosis and cardiomyopathy, as well as atypical or extrapulmonary tuberculosis are seen with increasing frequency. Mother to child transmission of HIV accounts for about 10% of total cases, with a transmission rate of 26% in two studies. Epidemiological and clinical research programs are well developed in Uganda, especially in areas of tuberculosis, maternal and paediatric HIV infection and sexually transmitted infections. Societal openness, a multisectoral approach by the government and innovative programmes, including large-scale HIV testing and counselling and the pioneering work of The AIDS Support Organization (TASO), distinguish the Ugandan response to the epidemic.

PIP: In 1982 the first cases of "slim disease" in Uganda were identified in Rakai District. This disease was not recognized as AIDS until 1985. AIDS is now a serious public health problem for Ugandans. Currently, about 1.5 million Ugandans have HIV infection, acquired mainly via heterosexual transmission; about 10% acquired HIV infection via the mother-child transmission route. In two studies, the mother-child HIV transmission rate reached 26%. 400,000-450,000 Ugandans have died from HIV/AIDS. HIV/AIDS is associated with the death of about 50% of adults in some areas of Uganda. Between 1993 and 1995, there has been a significant decrease in HIV seroprevalence among pregnant women in Kampala as well as in two rural communities. Cases and hospital admissions of tuberculosis (TB) have risen markedly in Uganda. Clinical manifestations of HIV infection include Kaposi's sarcoma, cryptococcal meningitis, toxoplasmosis, cardiomyopathy, and atypical or extrapulmonary TB. Uganda has well-developed HIV-focused epidemiologic and clinical research programs, particularly those addressing TB, maternal-child HIV transmission, and sexually transmitted diseases (STDs). The response to the HIV/AIDS epidemic in Uganda has been unique. The government has openly addressed it since the late 1980s, and this has opened the doors to the creation of innovative services for education, testing, and counseling and care for AIDS patients. Both the government and nongovernmental organizations have developed extensive HIV prevention programs. The AIDS Support Organization provides counseling and care for more than 35,000 persons with HIV/AIDS and has trained hundreds of counselors. Two possible reasons for the decline in the HIV seroprevalence that is now emerging in Uganda include: the AIDS epidemic either has reached a natural plateau or behavioral change has made a difference, improved treatment of STDs, and increasing availability and use of condoms has contributed to the reduction in HIV seroprevalence.