Godfrey Kigozi

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

ObjectiveTo assess mortality impact of HIV in rural Uganda. MethodsAn open cohort of 19u2005983 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. ResultsHIV 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 ⩾ 75%) and among government employees (PAF ⩾ 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. ConclusionHIV 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.

Measuring quality of life among HIV-infected women using a culturally adapted questionnaire in Rakai district, Uganda

To examine self-reported quality of life and health status of HIV-infected women and a comparison sample of HIV-uninfected women in rural Uganda, we culturally adapted a Lugandan version of the Medical Outcomes Survey-HIV (MOS-HIV). We administered a cross-sectional survey among 803 women (239 HIV-positive and 564 HIV-negative) enrolled in a community study to evaluate maternal and child health in Rakai District, Uganda. The interview took 20 minutes and was generally well-accepted. Reliability coefficients were >0.70, except for role functioning, energy and cognitive function. MOS-HIV scores for HIV-positive women were correlated with increasing number of physical symptoms and higher HIV viral load. Compared to HIV-negative women, HIV-positive women reported lower scores than HIV-negative women for general health perceptions, physical functioning, pain, energy, role functioning, social functioning, mental health and overall quality of life (p all <0.01). Substantial impairment was noted among women reporting ≥4 symptoms. In summary, HIV-positive women reported significantly poorer functioning and well-being than HIV-negative women. We conclude that patient-reported measures of health status and related concepts may provide a feasible, reliable and valid method to assess the impact of HIV/AIDS and future therapeutic interventions to improve patient outcomes in rural Africa.

Among 46 near full length HIV type 1 genome sequences from Rakai District, Uganda, subtype D and AD recombinants predominate.

The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. To minimize genetic diversity in the evaluation of HIV-1 vaccines, vaccine products must be matched to the predominant subtype in a vaccine cohort. To that end, full genome sequencing was used to detect and characterize HIV-1 subtypes and recombinant strains from individuals in Rakai District, Uganda. DNA extracted from peripheral blood mononuclear cells (PMBC) was PCR amplified using primers in the long terminal repeats (LTRs) to generate nearly full length genomes. Amplicons were directly sequenced with dye terminators and automated sequencers. Sequences were phylogenetically analyzed and recombinants were detected and mapped with distance scan and bootscan. Among 46 sequences, 54% were subtype D, 15% were subtype A, and 30% were recombinant. All recombinants were individually unique, and most combined subtypes A and D. Subtype D comprised more than 70% of all the HIV-1 genomes in Rakai when both pure subtypes and recombinants were considered. Candidate vaccines based on HIV-1 subtype D would be appropriate for evaluation in Rakai District, Uganda.

Factors associated with the prevalence and incidence of herpes simplex virus type 2 infection among men in Rakai Uganda.

Little is known about risk factors for incident herpes simplex virus type 2 (HSV-2) infection among men in Africa. In a trial in Rakai, Uganda, 6396 men aged 15-49 years were evaluated for serological evidence of HSV-2, human immunodeficiency virus (HIV), and syphilis infections at enrollment and at 6, 12, and 24 months. The prevalence of HSV-2 infection was 33.76%, and the incidence was 4.90 cases per 100 person-years. HSV-2 incidence increased with alcohol use with sexual intercourse (adjusted incidence rate ratio [adjIRR], 1.92 [95% confidence interval {CI}, 1.46-2.53]), decreased with consistent condom use (adjIRR, 0.56 [95% CI, 0.36-0.89]) and male circumcision (adjIRR, 0.70 [95% CI, 0.55-0.91]), and was not significantly affected by enrollment HIV status. Education on modifiable behavioral changes may reduce the acquisition of HSV-2. (ClinicalTrials.gov identifiers: NCT00425984 and NCT00124878 .).

Higher HIV-1 incidence and genetic complexity along main roads in Rakai District, Uganda

Objective:To determine the association between the incidence of HIV-1 infection and the genetic complexity of HIV-1 strains in 2 geographic strata within Rakai District, Uganda. Methods:Study volunteers with recent HIV-1 infections during the period 1997 through 2003 were recruited from 10 communities that were geographically stratified as a main road trading center (n = 5) or a secondary road trading village (n = 5). Cryopreserved plasma was available from 384 volunteers and was the source of viral RNA for genotyping by the multiregion hybridization assay. Hazard ratios (HRs) for a single HIV subtype, a recombinant form, or dual infection for gender and geographic strata were obtained using Cox proportional hazards analysis. Results:The HIV-1 incidence rate during the period 1999 through 2002 was 1.3 per 100 person-years (PYs) in the trading centers and 1.1 per 100 PYs in the trading villages. The HR for infection with an HIV-1 recombinant strain in trading centers relative to trading villages was 2.3 (95% confidence interval [CI]: 1.0 to 6.7). Among those who changed residence between village strata, the HR for a recombinant HIV-1 infection was 8.1 (95% CI: 0.4 to 47.7). Conclusions:HIV-1 incidence and genetic complexity are associated with geographic strata and population mobility in Rakai District and are important variables to be considered in planning and recruitment for vaccine trials.

Incident Hiv and herpes simplex virus type 2 infection among men in Rakai, Uganda

Objective:Herpes simplex virus type 2 (HSV-2) infection is associated with an increased risk for acquiring HIV, but little is known about the temporal sequence of these infections. Design:Six thousand three hundred ninety-six men were evaluated for serologic HSV-2 and HIV infections and behaviors during a male circumcision trial in Rakai, Uganda. Methods:HIV and HSV-2 status were determined using enzyme-linked immunosorbent assays and confirmed by HIV-1 and HSV-2 western blots. A Poisson multivariable model was used to estimate adjusted incidence rate ratios of HIV acquisition associated with HSV-2 and other covariates. Results:HIV incidence was 1.09/100 person-years and acquisition was associated with incident HSV-2 infection [adjusted incidence rate ratio (adjIRR) 5.28, 95% confidence interval (CI) 2.79–9.98], chronic HSV-2 infection (adjIRR 2.78, 95% CI 1.64–5.68), genital ulcer disease, urethral discharge, genital washing after intercourse, being unmarried, and being uncircumcised. Sixteen men acquired both HIV and HSV-2 during the trial: four acquired HIV first, three acquired HSV-2 first, and nine acquired both infections in the same follow-up interval. Conclusion:The findings suggest that unsafe sex places men at risk of both HIV and HSV-2 infections, and it is unclear whether HSV-2 acquisition is a cofactor for HIV infection or a marker of correlated sexual exposures. This reinforces the need for promotion of safe sex as the primary method of prevention of both viruses.

The number of procedures required to achieve optimal competency with male circumcision: findings from a randomized trial in Rakai, Uganda

To assess the number of procedures required to achieve optimal competency (time required for surgery with minimal adverse events) in Rakai, Uganda, and thus facilitate the development of guidelines for training providers, as male circumcision reduces the acquisition of human immunodeficiency virus (HIV) in men and is recommended for HIV prevention.

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.

Screening HIV-positive pregnant women for antiretroviral therapy: utility of self-reported symptoms

In developing countries, Mother-to-Child Transmission-Plus programmes propose to identify lifelong antiretroviral therapy (ART)-eligible women during antenatal care. Identification using AIDS-related symptoms is the most feasible screening procedure in resource-limited settings. It is not known if symptomatology in pregnant women is correlated with clinical criteria for ART initiation based on CD4+ cell count or HIV-1 viral load. In this population of HIV-positive pregnant women from Rakai District, Uganda, 8–23% were eligible for treatment by CD4+ cell count criteria, and <1% met WHO staging criteria for AIDS. Using one or more symptoms to predict CD4+ cell count <350 cells/mm3, sensitivity was 100%, specificity 11%, positive predictive value (PPV) 25%, and negative predictive value (NPV) 100%. When using one or more symptoms to predict viral load ≥100,000 cps/mL, sensitivity was 100%, specificity 10%, PPV 6%, and NPV 100%. Initiation of treatment based on self-reported symptoms will over-treat because the majority of pregnant women with symptoms would not be eligible for treatment under current guidelines, but asymptomatic pregnant women are unlikely to require ART.

Trichomonas vaginalis Incidence Associated with Hormonal Contraceptive Use and HIV Infection among Women in Rakai, Uganda

Background. Data on the incidence of Trichomonas vaginalis and use of hormonal contraception (HC) are limited. Methods. 2,374 sexually active women aged 15–49 years from cohort surveys in Rakai, Uganda, were included. Incidence of T. vaginalis was estimated per 100 person years (py) and association between HC (DMPA, Norplant, and oral contraceptives) and T. vaginalis infection was assessed by incidence rate ratios (IRR), using Poisson regression models. Results. At baseline, 34.9% had used HC in the last 12 months, 12.8% HIV+, 39.7% with high BV-scores (7–10), and 3.1% syphilis positive. The 12-month incidence of T. vaginalis was 2.4/100u2009py; CI (1.90, 3.25). When stratified by type of HC used, compared to women who did not use HC or condoms, incidence of T. vaginalis was significantly higher among users of Norplant (adj.IRR = 3.01, CI: 1.07–8.49) and significantly lower among DMPA users (adj.IRR = 0.55, CI: 0.30, 0.98) and women who discontinued HC use at follow-up (adj.IRR = 0.30, CI: 0.09, 0.99). HIV infection was associated with an increase in incidence of T. vaginalis (adj.IRR = 2.34, CI: 1.44, 3.78). Conclusions. Use of Norplant and being HIV+ significantly increased the risk of T. vaginalis, while use of DMPA and discontinuation of overall HC use were associated with a decreased incidence of T. vaginalis.