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.

Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda.

Human immunodeficiency virus (HIV) susceptibility is heterogenous, with some HIV-exposed but seronegative (HESN) individuals remaining uninfected despite repeated exposure. Previous studies in the cervix have shown that reduced HIV susceptibility may be mediated by immune alterations in the genital mucosa. However, immune correlates of HIV exposure without infection have not been investigated in the foreskin. We collected sub-preputial swabs and foreskin tissue from HESN (n=20) and unexposed control (n=57) men undergoing elective circumcision. Blinded investigators assayed swabs for HIV-neutralizing IgA, innate antimicrobial peptides, and cytokine levels. Functional T-cell subsets from foreskin tissue were assessed by flow cytometry. HESN foreskins had elevated α-defensins (3,027 vs. 1,795 pg ml(-1), P=0.011) and HIV-neutralizing IgA (50.0 vs. 13.5% of men, P=0.019). Foreskin tissue from HESN men contained a higher density of CD3 T cells (151.9 vs. 69.9 cells mm(-2), P=0.018), but a lower proportion of these was Th17 cells (6.12 vs. 8.04% of CD4 T cells, P=0.007), and fewer produced tumor necrosis factor α (TNFα) (34.3 vs. 41.8% of CD4 T cells, P=0.037; 36.9 vs. 45.7% of CD8 T cells, P=0.004). A decrease in the relative abundance of susceptible CD4 T cells and local TNFα production, in combination with HIV-neutralizing IgA and α-defensins, may represent a protective immune milieu at a site of HIV exposure.

Aetiology of genital ulcer disease in female partners of male participants in a circumcision trial in Uganda.

HIV acquisition is associated with herpes simplex virus type 2 (HSV-2) infection and genital ulcer disease (GUD). Three randomized control trials demonstrated that male circumcision significantly decreases HIV, HSV-2, human papillomavirus and self-reported GUD among men. GUD is also decreased among female partners of circumcised men, but it is unknown whether male circumcision status affects GUD pathogens in female partners. For the evaluation of GUD aetiology, two separate multiplex assays were performed to detect Haemophilus ducreyi, Treponema pallidum, HSV-1 and HSV-2. Of all the female GUD swabs evaluated, 67.5% had an aetiology identified, and HSV-2 was the primary pathogen detected (96.3%). However, there was no difference in the proportion of ulcers due to HSV-2 or other pathogens between female partners of circumcised men (11/15, 73.3%) compared with uncircumcised men (15/25, 60.0%, P = 0.39). The seroprevalence of HSV-2 is high in this population and therefore most of the detected HSV-2 infections represent reactivation. Since GUD is associated with HIV acquisition and one-third of GUD in this study did not have an aetiological agent identified, further research is needed to better understand the aetiology of GUD in Africa, and its relationship to circumcision and HIV infection.

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.

Comparison of STD prevalences in the Mwanza, Rakai, and Masaka trial populations: the role of selection bias and diagnostic errors.

OBJECTIVES: To assess bias in estimates of STD prevalence in population based surveys resulting from diagnostic error and selection bias. To evaluate the effects of such biases on STD prevalence estimates from three community randomised trials of STD treatment for HIV prevention in Masaka and Rakai, Uganda and Mwanza, Tanzania. METHODS: Age and sex stratified prevalences of gonorrhoea, chlamydia, syphilis, HSV-2 infection, and trichomoniasis observed at baseline in the three trials were adjusted for sensitivity and specificity of diagnostic tests and for sample selection criteria. RESULTS: STD prevalences were underestimated in all three populations because of diagnostic errors and selection bias. After adjustment, gonorrhoea prevalence was higher in men and women in Mwanza (2.8% and 2.3%) compared to Rakai (1.1% and 1.9%) and Masaka (0.9% and 1.8%). Chlamydia prevalence was higher in women in Mwanza (13.0%) compared to Rakai (3.2%) and Masaka (1.6%) but similar in men (2.3% in Mwanza, 2.7% in Rakai, and 2.2% in Masaka). Prevalence of trichomoniasis was higher in women in Mwanza compared to women in Rakai (41.9% versus 30.8%). Herpes simplex virus type 2 (HSV-2) seroprevalence and prevalence of serological syphilis (TPHA+/RPR+) were similar in the three populations but the prevalence of high titre syphilis (TPHA+/RPR >/=1:8) in men and women was higher in Mwanza (5.6% and 6.3%) than in Rakai (2.3% and 1.4%) and Masaka (1.2% and 0.7%). CONCLUSIONS: Limited sensitivity of diagnostic and screening tests led to underestimation of STD prevalence in all three trials but especially in Mwanza. Adjusted prevalences of curable STD were higher in Mwanza than in Rakai and Masaka.

The effect of HIV, behavioural change, and STD syndromic management on STD epidemiology in sub-Saharan Africa: simulations of Uganda.

An assessment was made of how the HIV epidemic may have influenced sexually transmitted disease (STD) epidemiology in Uganda, and how HIV would affect the effectiveness of syndromic STD treatment programmes during different stages of the epidemic. The dynamic transmission model STDSIM was used to simulate the spread of HIV and four bacterial and one viral STD. Model parameters were quantified using demographic, behavioural, and epidemiological data from rural Rakai and other Ugandan populations. The findings suggest that severe HIV epidemics can markedly alter STD epidemiology, especially if accompanied by a behavioural response. Likely declines in bacterial causes of genital ulcers should be considered in defining policies on syndromic STD management in severe HIV epidemics.

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.

Randomized trial of presumptive sexually transmitted disease therapy during pregnancy in Rakai, Uganda.

OBJECTIVE: The purpose of this study was to assess presumptive sexually transmitted disease treatment on pregnancy outcome and HIV transmission. STUDY DESIGN: In a randomized trial in Rakai District, Uganda, 2070 pregnant women received presumptive sexually transmitted disease treatment 1 time during pregnancy at varying gestations, and 1963 control mothers received iron/folate and referral for syphilis. Maternal-infant sexually transmitted disease/HIV and infant outcomes were assessed. Intent-to-treat analyses estimated adjusted rate ratios and 95% confidence intervals. RESULTS: Sexually transmitted diseases were reduced: Trichomonas vaginalis (rate ratio, 0.28; 95% CI, 0.18%-0.49%), bacterial vaginosis (rate ratio, 0.78; 95% CI, 0.69-0.87), Neisseria gonorrhoeae /Chlamydia trachomatis (rate ratio, 0.43; 95% CI, 0.27-0.68), and infant ophthalmia (rate ratio, 0.37; 95% CI, 0.20-0.70). There were reduced rates of neonatal death (rate ratio, 0.83; 95% CI, 0.71-0.97), low birth weight (rate ratio, 0.68; 95% CI, 0.53-0.86), and preterm delivery (rate ratio, 0.77; 95% CI, 0.56-1.05); but there were no effects on maternal HIV acquisition or perinatal HIV transmission. CONCLUSION: Reductions of maternal sexually transmitted disease improved pregnancy outcome but not maternal HIV acquisition or perinatal HIV transmission.

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.

Prevalence of Kaposi sarcoma-associated herpesvirus compared with selected sexually transmitted diseases in adolescents and young adults in rural Rakai District, Uganda.

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is transmitted by routes such as homosexual intercourse and is associated with HIV infection in industrialized countries. However, there is little information about its transmission in developing countries where Kaposi sarcoma is an endemic disease. GOAL: To examine KSHV seroprevalence in young adults in a general, rural Ugandan population, and to compare this prevalence with rates of known sexually transmitted infections. STUDY DESIGN: The seroprevalence of KSHV was compared with the epidemiology of sexually transmitted diseases in 523 sexually active subjects aged 15 to 29 years who were randomly selected from a general population cohort in rural Rakai District, Uganda. Participants provided in-home interview data and specimens. Sera were tested for KSHV using immunofluorescence assay and immunoblot for lytically expressed recombinant KSHV ORF65.2. Sera were also tested for HIV type 1, herpes simplex virus type 2, and syphilis. RESULTS: The prevalence of KSHV was significantly higher in participants 15 to 19 years compared with older persons 25 to 29 years (45.0% and 36.1%, respectively; adjusted odds ratio, 0.48; 95% CI, 0.28-0.82). In contrast, herpes simplex virus type 2 and HIV type 1 prevalence increased with age. Kaposi sarcoma-associated herpesvirus serostatus was not associated with HIV type 1, syphilis, herpes simplex virus type 2, or number of sexual partners. Homosexual and anal intercourse were reported by less than 1% of participants. CONCLUSIONS: Kaposi sarcoma-associated herpesvirus does not appear to be a heterosexually transmitted infection in rural Uganda.

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.

Condom acceptance is higher among travelers in Uganda.

OBJECTIVE: To examine the role played by mobile residents in the spread of HIV through rural Uganda. DESIGN: Travel history and sexual network data were collected from a random sample of 1627 residents aged 15-49 years in Rakai District, Uganda during 1994. METHODS: Travelers and non-travelers are compared with respect to socio-demographic attributes, risk exposure, knowledge, attitudes and use of condoms using descriptive statistics and multivariate logistic regression. A demographic profile of travelers' partners is developed using information from a local network survey module. RESULTS: The population is highly mobile, with over 70% reporting travel to a potentially higher risk destination in the past year. Travelers are somewhat more likely to have higher levels of sexual risk behavior, but the risk appears to be offset by significantly greater knowledge, acceptance, and use of condoms. In multivariate analysis, the sexual risk differential for travelers is explained by occupational exposure and higher socio-economic status. The differential in condom acceptance, by contrast, appears to be associated with travel itself. Condom use with non-spousal partners is three times higher among travelers than non-travelers (P< 0.001), and travel remains a significant predictor after controlling for age, education, residence, occupation and multiple partners. Travelers are more likely to use condoms with both their local and non-local partners. Partners of male travelers are likely to be younger and better educated than those of male non-travelers. CONCLUSIONS: The mobile population in this rural region appears willing to adopt risk reduction measures appropriate to their exposure. This suggests that targeting condom promotion programs to travelers and their partners is likely to be effective in reducing the spatial diffusion of HIV, and may be an efficient method for spreading behavioral change into rural areas.

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.

Sero-prevalence of Herpes simplex virus type 2 (HSV-2) in Rakai district, Uganda.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is sexually transmitted and causes one of the genital ulcerative diseases associated with the transmission of human immunodeficiency virus type I (HIV-1). OBJECTIVE: To determine the prevalence of serological reactivity to a type specific HSV-2 antigen (gG2) ELISA assay. SETTING: Rakai district, Uganda. SUBJECTS: Two hundred and one serum samples of persons aged 15-54 years. The samples were randomly selected by a computer programme. RESULTS: Out of the 201 serum samples selected, 117 (58.2%) had serological evidence of HSV-2 infection. Twenty nine (32.2%) out of the 74 males and 88 (69.3%) out of the 127 females, respectively, had serological evidence of HSV-2 infection giving a female:male ratio of 1.8 (95% CI 1.3-2.4). The most important risk factor for acquisition of HSV-2 in males was found to be age while in the females, the most important risk factors were age and the number of sexual partners in the previous five years. CONCLUSION: HSV-2 was highly prevalent in this rural population of Uganda.