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This study explored men's views of workplace-based HIV self-testing and the barriers and facilitators of linkage to posttest services. Six focus group discussions and individual in-depth interviews were held with employers and employees in private security companies in Uganda (N = 70). Using content analysis, five categories emerged. The first category was the mitigation of potential harm, including reduction of stigma and discrimination, and the need for posttest support. The second category was a perceived need for on-site services where the men proposed on-site prevention services and HIV treatment and care. In the third category, which was strengthening linkage mechanisms, participants proposed expanded clinic hours, improved health facility efficiency, and provision of referral documentation. The fourth and fifth categories were organizational support and social support, respectively. There is need for employers and employees to work together for the success of workplace-based HIV initiatives.

Objective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls. Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFNγ) production in response to K562 cells, or interleukin (IL)-12 and IL-18. Results: CD56dim NK cells from HIV-infected individuals produced less IFNγ in response to IL-12 and IL-18 than did CD56dim NK cells from uninfected controls. Infected individuals had lower levels of CD56dim NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A+CD57+ CD56dim NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFNγ production correlated directly with coexpression of CD57 and NKG2A on CD56dim NK cells. Conclusion: HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A+CD57+ CD56dim NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans.

OBJECTIVE: Studies suggest that the prevalence of HIV is higher among long-term marital/consensual relationships than in the unmarried. We assessed the risk of incident HIV infection by marital status in rural Rakai Uganda. DESIGN: Longitudinal data from the Rakai Community Cohort Study between 1999 and 2011. METHODS: We estimated HIV incidence per 100 person years (py) in sexually active individuals aged 15-49 years with a total of 44179.6 py who were never married (women 2929 py and men 4261 py) currently married or in long-term consensual relationships (currently married women 29823 py and men 21299 py) and previously married (women 3563 py and men 1475). Poisson multivariable regression was used to estimate the unadjusted and adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of HIV acquisition. RESULTS: The HIV incidence among currently married persons was 0.93/100 py which was lower than that for the never-married (1.51/100 py) and previously married (2.85/100 py) persons. The risk of HIV acquisition was significantly lower in the currently married compared with that in the never married among women (Adj IRR = 0.26 95% CI: 0.16 to 0.42) but not among men (Adj IRR = 0.69 95% CI: 0.31 to 1.52). HIV incidence was lower among first marriages (0.73/100 py) compared with that among second- or higher-order marriages (1.38/100 py). Multiple sex partners significantly increased the risk of HIV acquisition in both women (Adj IRR = 2.53 95% CI: 1.6 to 3.97) and men (Adj IRR = 1.77 95% CI: 1.20 to 2.60). CONCLUSIONS: Current marriage especially first-order marriage was associated with a reduced risk of HIV acquisition in women but not in men and multiple sex partnerships increased HIV risk for both sexes.

OBJECTIVES Medical male circumcision (MMC) is recommended for HIV prevention in men. We assessed the acceptability and safety of the Shang Ring device compared with those of the dorsal slit method. METHODS HIV-negative, uncircumcised men aged 18 years or older who requested free MMC services in rural Rakai, Uganda, were informed about the Shang Ring and dorsal slit procedures and offered a free choice of procedure. Men were followed at 7 days postoperatively to assess adverse events related to surgery and to remove the Shang Ring. Wound healing was assessed at 4 weeks postoperatively. RESULTS Six hundred twenty-one men were enrolled, of whom 508 (81.8%) chose the Shang Ring and 113 the dorsal slit. The Shang Ring was provided to 504 men, among whom there were 4 failures of Ring placement (0.8%) that required surgical hemostasis and wound closure. Five hundred men received the Shang Ring and postoperative surgery-related moderate adverse events were 1.0%, compared with 0.8% among dorsal slit recipients. Complete wound healing at 4 weeks was 84% with the Ring and 100% with the dorsal slit (P < 0001). Resumption of intercourse before 4 weeks was 7.0% with the Ring and 15.0% with the dorsal slit (P = 0.01.) The mean time for surgery was 6.1 minutes with the Ring and 17.7 minutes with the dorsal slit. The mean time for Ring removal was 2.2 minutes. CONCLUSIONS The Shang Ring is highly acceptable and safe in this setting, and could improve the efficiency of MMC services. However, back-up surgical services are needed in cases of Ring placement failures.

HIV-1 subtype D is associated with faster disease progression compared with subtype A. Immunological correlates of this difference remain undefined. We investigated invariant natural killer T (iNKT) cells and FoxP3⁺ regulatory T cells (Tregs) in Ugandans infected with either subtype. Loss of iNKT cells was pronounced in subtype D, whereas Tregs displayed more profound loss in subtype A infection. The iNKT cell levels were associated with CD4 T-cell interleukin-2 production in subtype A, but not in D, infection. Thus, these viral subtypes are associated with differential loss of iNKT cells and Tregs that may influence the quality of the adaptive immune response.

BACKGROUND Large datasets for investigating vaginal flora change at frequent, repeated intervals are limited and graphical methods for exploring such data are inadequate. We report 2-year weekly vaginal flora changes based on Gram stain using lasagna plots. METHODS Weekly vaginal flora patterns were evaluated among 211 sexually experienced women with ≥18 months of follow-up in Rakai, Uganda. Vaginal flora swabs were self-collected weekly and categorized by Nugent Gram stain criteria (0-3, normal; 4-6, intermediate; 7-10, bacterial vaginosis [BV]). Vaginal flora patterns were analyzed as the percentage of weekly observations with BV (longitudinal prevalence) and illustrated by lasagna plots. Characteristics of women were compared across tertiles of longitudinal prevalence of BV. RESULTS Ninety-five percent of women had at least 1 episode of BV over 2 years, with one-third of women spending more than half (52%-100%) of their time with BV. Vaginal pH >4.5 increased with increasing tertiles of longitudinal prevalence of BV (P < 0.001). Weekly fluctuation in vaginal flora states, as measured by a change in flora states from the before current visit, was highest in the middle (41.9%) compared with the lower (30.1%) and upper tertiles (27.8%, P < 0.001). HIV status and reported vaginal symptoms did not differ significantly across BV tertiles. CONCLUSIONS Women exhibited different patterns of vaginal flora changes over time, which could not be described by baseline behaviors. Lasagna plots aided in describing the natural history of BV within and across women and may be applied to future BV natural history studies.

Objective To assess the impact of HIV and malaria coinfection on mother-to-child HIV transmission (MTCT) and adverse birth outcomes. Methods One hundred nine HIV-positive mother-infant pairs with a malaria diagnosis were identified in a community cohort and followed up postpartum. Maternal malaria was diagnosed by a rapid immunochromatographic test (ICT) on sera and histopathologic examination of placenta. Infant HIV was diagnosed within 6 weeks of birth using polymerase chain reaction (PCR) to capture in-utero and intrapartum HIV transmission. Log binomial models were used to assess the relative risk of MTCT, low birth weight, and preterm birth associated with malaria. Results Approximately 17.4% of infants were HIV positive at or around birth, and the prevalence of serologic and placental malaria were 31% and 32%, respectively. HIV-positive mothers with serological ICT malaria were significantly more likely to have low-birth-weight infants, and low-birth-weight infants had significantly higher risk of MTCT compared with infants of normal birth weight. Although placental and serologic ICT malaria were significantly associated with MTCT, after adjusting for maternal HIV viral load, the risk of MTCT was significantly increased only for mothers coinfected with placental malaria (relative risk [RR] = 7.9, P = 0.025). Conclusions Placental malaria increases the risk of MTCT after adjustment for viral load. Programs should focus on enhanced malaria prevention during pregnancy to decrease the risk of adverse birth outcomes and MTCT.

There are limited empirical data on the prevalence and incidence of orphanhood due to parental HIV infection. The objective was to assess the prevalence and incidence of orphanhood and the population attributable fraction (PAF) of incident orphanhood associated with parental HIV infection in a rural population with a 14.8% adult HIV prevalence. The data are derived from a community cohort in Rakai District Uganda. Census data were collected on all resident members in 10 657 households including survival of parents of resident children in 1996/1997. Consenting adults were interviewed provided blood for HIV testing and were followed up 10 months later to determine parental death and incident orphanhood. The incidence rate ratio (IRR) of orphanhood associated with parental HIV-infection was estimated by Poisson multivariate regression. A total of 22 712 children aged 0–14 years were enumerated in 1996/1997. The overall prevalence of orphanhood was higher among children of HIV-infected parents (22.7%) compared with children of uninfected parents 7.9%. The annual incidence of orphanhood was 8.2% if at least one parent was HIV positive and 0.5% if both parents were HIV negative (adjusted IRR = 18.93). Older age of children and older maternal age were significantly associated with an increased risk of orphanhood. The PAF of incident orphanhood due to parental HIV infection was 37.3% and was highest among younger children (adjusted PAF = 50.6% for 0–4 year olds) and children with younger mothers aged < 25 years (adjusted PAF = 75.7%). Parental HIV infection markedly increased the incidence of orphanhood especially among younger children and the children of younger mothers. (authors)

Objective: The goal of this study was to assess azithromycin and/or benzathine penicillin for treatment of syphilis. Methods: In a population-based study, participants with serologic syphilis (TRUST with TPHA confirmation) were offered 2.4 MU benzathine penicillin intramuscularly. Intervention arm participants received 1 g presumptive oral azithromycin. We assessed cure rates with penicillin or azithromycin given alone and in combination. Cure assessed after 10 months was defined as seroreversion or a 4-fold decrease in titer. The rate ratio (RR) of cure and 95% confidence intervals (95% CIs) were estimated by log binomial regression. Results: Among 952 cases with syphilis, 18% received penicillin alone, 17% azithromycin only, and 65% dual treatment. The overall cure rate was 61%. Cure rates were lower in males compared with females (RR, 0.89; 95% CI, 0.80‐0.99) and in subjects with initial titers >1:4 compared with 1:4, significantly higher cure rates were observed with azithromycin alone (adjusted RR, 1.38; 95% CI, 0.97‐1.96), and with dual treatment of azithromycin and benzathine penicillin (RR, 1.38; 95% CI, 1.03‐1.87) compared with penicillin alone. Conclusion: Azithromycin alone or in combination with penicillin achieved higher cure rates than penicillin alone in cases with a high initial TRUST titer. In low-titer infections, the 3 drug combinations were equally effective. HIV status did not affect cure rates. GENITAL ULCER DISEASE (GUD), caused by primary and secondary syphilis has been associated with increased infectiousness of and susceptibility to HIV, and syphilis, particularly in pregnancy, is a major public health problem. 1,2 Benzathine penicillin has long been the standard treatment for syphilis, but studies have established that azithromycin is effective and may be useful for the control of syphilis in high-risk populations or during epidemics. 3– 8 Azithromycin has the added advantage of oral administration rather than intramuscular injection. Also, there is limited information on whether HIV infection affects the response to syphilis treatment in developing countries, although previous studies in developed countries suggest that HIV infection has relatively modest effects on cure rates. 9,10

Objectives: To assess whether differences in age between sexual partners affect the risk of HIV infection in female adolescents and young adults. Methods: A total of 6177 ever sexually active women aged 15 to 29 years completed a sociodemographic and sexual behavior questionnaire and provided a blood sample for HIV-1 serology. The age difference between partners was categorized as men 0 to 4 years older (referent group) 5 to 9 years older and 10 or more years older. HIV prevalence and incidence were assessed and adjusted RR was estimated by multivariate regression. Results: Prevalent HIV-1 infection in female participants increased with older male sexual partners. Among women aged 15 to 19 years the adjusted risk of HIV infection doubled (RR = 2.04; 95% CI: 1.29–3.22) among those reporting male partners 10 or more years older compared with those with male partners 0 to 4 years older; among women 20 to 24 years of age the RR was 1.24 (95% CI: 0.96–1.60). The attributable fraction (exposed) of prevalent HIV infection in women aged 15 to 24 years associated with partners 10 or more years older was 9.7% (95% CI: 5.2–14.0). HIV incidence did not increase with differences in age of partners. Conclusion: The age difference between young women and their male partners is a significant HIV risk factor suggesting that high HIV prevalence in younger women is caused in part by transmission from older male partners. (authors)

The aim of this study was 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. A 1994-95 community-randomized trial in the Rakai District of Uganda enrolled adults aged 15-59 years and ascertained their HIV status sociodemographic characteristics risk behaviors and AIDS-associated symptoms. All subjects were offered confidential individual VTC at no cost. The authors compared users and nonusers of VTC among 10950 participants (4764 male and 6186 female) enrolled at baseline using multivariate logistic regression. Women were significantly less likely to receive VTC than men (31.5% versus 34.8% p < 0.001). 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. During the initial phase of a population-based free VTC program in rural Uganda certain high-risk groups were under-represented among VTC recipients. There is a need to target VTC to ensure participation by high-risk individuals most in need of services. (authors)

Evidence of condom effectiveness for HIV and sexually transmitted disease (STD) prevention is based primarily on high-risk populations. The authors examined condom effectiveness in a general population with high HIV prevalence in rural Africa. Data were from a randomized community trial in Rakai Uganda. Condom usage information was obtained prospectively from 17264 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 (ORs) of STDs estimated by logistic regression. 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 (OR 0.71; 95% CI 0.53-0.94) and gonorrhea/Chlamydia (OR 0.50; 95% CI; 0.25-0.97) after adjustment for sociodemographic 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. 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. (authors)

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.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.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.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.Kaposi sarcoma-associated herpesvirus does not appear to be a heterosexually transmitted infection in rural Uganda.

To assess mortality impact of HIV in rural Uganda.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.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 (PAF80%) and in women. HIV associated mortality was highest in the better educated (PAFor = 75%) and among government employees (PAFor = 82%). Of the HIV-positive subjects 40.5% reported no illness10 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.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.

Male circumcision is associated with reduced HIV acquisition. 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. 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 seroconversions occurred in 50 circumcised men whereas HIV acquisition was 16.7/100 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 of

To assess whether circumcision performed on postpubertal men affords the same level of protection from HIV-1 acquisition as circumcisions earlier in childhood.Cross-sectional study of a population-based cohort.Rakai district, rural Uganda.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 andor = 21 years.HIV-1 prevalence was 14.1% in uncircumcised men, compared with 16.2% for men circumcised at ageor = 21 years, 10.0% for men circumcised at age 13-20 years, and 6.9% in men circumcised at ageor = 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.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.

We examined the association of placental malaria and mother-to-child transmission (MTCT) of HIV in a prospective community-randomized trial in Rakai District, Uganda. In the 746 HIV-positive mother-infant pairs, the MTCT rate was 20.4%. Placental malaria was more common in HIV-positive than HIV-negative women. After multivariate adjustment for HIV viral load, the risk of MTCT associated with placental malaria was 2.89 and with HIV viral load the risk was 2.85. Interventions to prevent malaria during pregnancy could potentially reduce MTCT.

A study was conducted in Rakai Uganda to evaluate the urine HIV-1 test. 222 subjects provided paired concurrent urine and serum samples at a single study visit between 1996 and 1997. The samples 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 prepared on stored refrigerated urine at Johns Hopkins University (JHU) and on fresh specimens at the Rakai Project laboratory. The sensitivity and specificity of the urine assay were determined using serum EIA and WB assay results as the reference test. Out of the 96 serum HIV-positive results 92 were detected by urine EIA/WB giving a sensitivity of 95.8%. Of the 94 fresh urine samples all were positive on EIA and confirmed by WB giving a sensitivity of 100%. Among serum HIV-negative subjects all frozen urine samples were negative at JHU and 97.7% of fresh samples were negative at RP. The differences in sensitivity and specificity between the fresh and frozen samples were not statistically significant. In conclusion the results indicated that the Calypte urine HIV-1 EIA/WB is sensitive and specific as compared with the testing of serum samples.

The authors previously published a paper on HIV risk factors in Rakai district Uganda in which they found the population-attributable risk fraction (PARF) associated with multiple sex partners to be substantially higher than the PARF associated with an history of sexually transmitted diseases (STD). C.P. Hudson in a subsequent letter held these findings to suggest that programs which promote behavioral change may be more critical than STD control in reducing the incidence of HIV. While the researchers and authors of these earlier findings support the importance of behavior change in AIDS prevention they herewith argue that it is premature to make policy decisions on the relative value of programs emphasizing behavior modification rather than STD control. STD data in the study was based on the recall of study subjects and not direct serological or physical examination and evidence. Data suggests that previous STD may be underreported more frequently than recent events. Additionally research supports the tendency of women interviewed in the study to underreport their number of casual partners. Underreporting one or both variables will distort or weaken the association noted in the original paper. The authors therefore stress the need to collect more information through a variety of mechanisms before determining the feasibility and effectiveness of implementing different HIV prevention strategies. It must also be remembered that prevention strategies are interlinked. Finally the authors note their interest in the hypothesis that concurrent partnerships may play a greater role in HIV transmission than absolute numbers of partners.

This article focuses on some practical aspects on the care of HIV-infected people in the developing world. Perception of HIV infection is changing. In developing countries, health care providers have the ethical obligation to care for HIV patients even with the scarcity of resources. Considering the complex administrative, medical, political, economic and ethical issues involved in providing care, a national strategy with treatment guidelines is an important component of AIDS programs. Moreover, constraints in resources and the local sociocultural aspects should be taken into account when choosing strategies. Treatment strategies should emphasize a compassionate, low technology, and cost-effective care. This paper explores on the diagnostic process and treatment of HIV/AIDS. To maximize efficiency and ensure treatment continuity, care of HIV patients should observe the following levels of care: home and community-based care, HIV clinic care, and in-patient care. Though, there is no cure for HIV infection, the disease can be treated, thereby improving the overall quality of life of the patient, provided there is a will, love and compassion on the part of caregivers.