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.

Evaluation of Chiron HIV-1/HIV-2 recombinant immunoblot assay.

In a study to determine the reliability, sensitivity, and specificity of the Chiron RIBA HIV-1/HIV-2 Strip Immunoblot Assay (RIBA HIV-1/2 SIA) for confirmation of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies, 1,263 serum samples from various populations in the United States, Caribbean, Africa, India, and Thailand were evaluated by RIBA HIV-1/2 SIA, and the results were compared with those obtained by an HIV-1 Western blot (immunoblot) assay. All sera were tested by HIV enzyme immunoassay, RIBA HIV-1/2 SIA, and Western blotting. Samples with discrepant results were further tested by an HIV-1 and/or HIV-2 immunofluorescent-antibody assay and HIV-1 p24 antigen assay. The RIBA HIV-1/2 SIA detected all 17 HIV-1 and HIV-2 dually reactive serum samples, all 215 HIV-2-positive serum samples, and 480 of 481 HIV-1-positive serum samples for a sensitivity of 99.8%. Of 548 negative samples, 523 were RIBA HIV-1/2 SIA negative, for a specificity of 95.4%, with 22 (4%) samples interpreted as indeterminate and 3 (0.6%) interpreted as falsely positive. Western blotting detected 391 of 548 negative samples (specificity, 71.4%), with 152 (27.7%) samples interpreted as indeterminate and 5 (0.9%) interpreted as falsely positive. In conclusion, the RIBA HIV-1/2 SIA had a sensitivity comparable to that of Western blotting and could discriminate HIV-1 from HIV-2 in one blot, providing a cost advantage. Because of its high degree of specificity, the RIBA HIV-1/2 SIA further reduced the number of indeterminate results found by Western blotting, providing a more accurate means of assessing seronegative individuals.

Asymptomatic non-ulcerative genital tract infections in a rural Ugandan population.

OBJECTIVE: To document the prevalence of asymptomatic non-ulcerative genital tract infections (GTI) in a rural African cohort. METHODS: The study population consisted of all adults aged 15-59 residing in 56 rural communities of Rakai District, southwest Uganda, enrolled in the Rakai STD Control for AIDS Prevention Study. Participants were interviewed about the occurrence of vaginal or urethral discharge and frequent or painful urination in the previous 6 months. Respondents were asked to provide blood and a first catch urine sample. Serum was tested for HIV-1. Urine was tested with ligase chain reaction (LCR) for N gonorrhoeae and C trachomatis. Women provided two self administered vaginal swabs; one for T vaginalis culture and the other for a Gram stained slide for bacterial vaginosis (BV) diagnosis. RESULTS: A total of 12,827 men and women were enrolled. Among 5140 men providing specimens, 0.9% had gonorrhoea and 2.1% had chlamydia. Among 6356 women, 1.5% had gonorrhoea, 2.4% had chlamydia, 23.8% were infected with trichomonas and 50.9% had BV.53% of men and 66% of women with gonorrhoea did not report genital discharge or dysuria at anytime within the previous 6 months. 92% of men and 76% of women with chlamydia and over 80% of women with trichomonas or BV were asymptomatic. The sensitivities of dysuria or urethral discharge for detection of infection with either gonorrhoea or chlamydia among men were only 21.4% and 9.8% respectively; similarly, among women the sensitivity of dysuria was 21.0% while that of vaginal discharge was 11.6%. For trichomonas or BV the sensitivity of dysuria was 11.7% and that of vaginal discharge was 10.5%. CONCLUSION: The prevalence of non-ulcerative GTIs is very high in this rural African population and the majority are asymptomatic. Reliance on reported symptoms alone would have missed 80% of men and 72% of women with either gonorrhoea or chlamydia, and over 80% of women with trichomonas or BV. To achieve STD control in this and similar populations public health programmes must target asymptomatic infections.

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.

Population-based study of fertility in women with HIV-1 infection in Uganda.

BACKGROUND: To assess the effects of HIV-1 and other sexually transmitted infections on pregnancy, we undertook cross-sectional and prospective studies of a rural population in Rakai district, Uganda. METHODS: 4813 sexually active women aged 15-49 years were surveyed to find out the prevalence of pregnancy by interview and selective urinary human chorionic gonadotropin tests. The incidence of recognised conception and frequency of pregnancy loss were assessed by follow-up. Samples were taken to test for HIV-1 infection, syphilis, and other sexually transmitted diseases. FINDINGS: At time of survey 757 (21.4%) of 3544 women without HIV-1 infection or syphilis were pregnant, compared with 46 (14.6%) of 316 HIV-1-negative women with active syphilis, 117 (14.2%) of 823 HIV-1-positive women with no concurrent syphilis, and 11 (8.5%) of 130 women with both syphilis and HIV-1 infection. The multivariate adjusted odds ratio of pregnancy in HIV-1-infected women was 0.45 (95% CI 0.35-0.57); the odds of pregnancy were low both in HIV-1-infected women without symptoms (0.49 [0.39-0.62]) and in women with symptoms of HIV-1-associated disease (0.23 [0.11-0.48]). In women with concurrent HIV-1 infection and syphilis the odds ratio was 0.28 (0.14-0.55). The incidence rate of recognised pregnancy during the prospective follow-up study was lower in HIV-1-positive than in HIV-1-negative women (23.5 vs 30.1 per 100 woman-years; adjusted risk ratio 0.73 [0.57-0.93]). Rates of pregnancy loss were higher among HIV-1-infected than uninfected women (18.5 vs 12.2%; odds ratio 1.50 [1.01-2.27]). The prevalence of HIV-1 infection was significantly lower in pregnant than in non-pregnant women (13.9 vs 21.3%). INTERPRETATION: Pregnancy prevalence is greatly reduced in HIV-1-infected women, owing to lower rates of conception and increased rates of pregnancy loss. HIV-1 surveillance confined to pregnant women underestimates the magnitude of the HIV-1 epidemic in the general population.

PIP: A cross-sectional, prospective study conducted in Uganda's rural Rakai District indicated pregnancy prevalence is substantially reduced in women infected with HIV. A total of 4813 women 15-49 years of age who had at least one sexual partner in the previous year and were unaware of their HIV status were enrolled. 953 women (19.8%) were HIV-positive and 446 (9.3%) were diagnosed with active syphilis. 931 women (19.3%) became pregnant during the study period (1989-92). The pregnancy rate was 21.4% among women with no serologic evidence of HIV or syphilis compared with 14.6% among HIV-negative women with active syphilis and 8.5% among women infected with both HIV and syphilis. The pregnancy rate also was significantly higher among the 833 asymptomatic HIV-infected women (14.3%) than the 120 with clinical symptoms (7.5%). Symptomatic HIV-1 infection in male partners did not account for the lower pregnancy rate in HIV-positive women. After controls for age, marital status, gravidity, contraceptive use, lactation, subfertility, and time since last intercourse, the adjusted odds ratio of pregnancy among all HIV-positive women compared to women without HIV or syphilis was 0.45 (95% confidence interval, 0.35-0.57). Among the 3340 women who were not pregnant at baseline and were locatable, the pregnancy rate during follow-up was 23.5 per 100 woman-years among HIV-positive women and 30.1 per 100 woman-years among those without HIV or syphilis. Rates of pregnancy loss were higher among HIV-infected women (18.5%) than HIV-negative women (12.2%). The prevalence of HIV-1 infection was significantly lower in pregnant than nonpregnant women (13.9% and 21.3%, respectively). These findings indicate that, if HIV surveillance is confined to pregnant women, the prevalence of HIV-1 among women of reproductive age will be seriously underestimated.