208 research outputs found

    Does biological relatedness affect child survival?

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    Objective: We studied child survival in Rakai, Uganda where many children are fostered out or orphaned. Methods: Biological relatedness is measured as the average of the Wright’s coefficients between each household member and the child. Instrumental variables for fostering include proportion of adult males in household, age and gender of household head. Control variables include SES, religion, polygyny, household size, child age, child birth size, and child HIV status. Results: Presence of both parents in the household increased the odds of survival by 28%. After controlling for the endogeneity of child placement decisions in a multivariate model we found that lower biological relatedness of a child was associated with statistically significant reductions in child survival. The effects of biological relatedness on child survival tend to be stronger for both HIV- and HIV+ children of HIV+ mothers. Conclusions: Reductions in the numbers of close relatives caring for children of HIV+ mothers reduce child survival.AIDS/HIV, child survival, fostering, orphans, Uganda

    Penile anaerobic dysbiosis as a risk factor for HIV infection

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    Sexual transmission of HIV requires exposure to the virus and infection of activated mucosal immune cells, specifically CD4+ T cells or dendritic cells. The foreskin is a major site of viral entry in heterosexual transmission of HIV. Although the probability of acquiring HIV from a sexual encounter is low, the risk varies even after adjusting for known HIV risk factors. The genital microbiome may account for some of the variability in risk by interacting with the host immune system to trigger inflammatory responses that mediate the infection of mucosal immune cells. We conducted a case-control study of uncircumcised participants nested within a randomized-controlled trial of male circumcision in Rakai, Uganda. Using penile (coronal sulcus) swabs collected by study personnel at trial enrollment, we characterized the penile microbiome by sequencing and real-time PCR and cytokine levels by electrochemiluminescence assays. The absolute abundances of penile anaerobes at enrollment were associated with later risk of HIV seroconversion, with a 10-fold increase in Prevotella, Dialister, Finegoldia, and Peptoniphilus increasing the odds of HIV acquisition by 54 to 63%, after controlling for other known HIV risk factors. Increased abundances of anaerobic bacteria were also correlated with increased cytokines, including interleukin-8, which can trigger an inflammatory response that recruits susceptible immune cells, suggesting a mechanism underlying the increased risk. These same anaerobic genera can be shared between heterosexual partners and are associated with increased HIV acquisition in women, pointing to anaerobic dysbiosis in the genital microbiome and an accompanying inflammatory response as a novel, independent, and transmissible risk factor for HIV infection. IMPORTANCE We found that uncircumcised men who became infected by HIV during a 2-year clinical trial had higher levels of penile anaerobes than uncircumcised men who remained HIV negative. We also found that having higher levels of penile anaerobes was also associated with higher production of immune factors that recruit HIV target cells to the foreskin, suggesting that anaerobes may modify HIV risk by triggering inflammation. These anaerobes are known to be shared by heterosexual partners and are associated with HIV risk in women. Therefore, penile anaerobes may be a sexually transmissible risk factor for HIV, and modifying the penile microbiome could potentially reduce HIV acquisition in both men and women

    The long-term effects of a family based economic empowerment intervention (Suubi+Adherence) on suppression of HIV viral loads among adolescents living with HIV in southern Uganda: Findings from 5-year cluster randomized trial

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    BACKGROUND: The rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment. METHODS: We carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect of a family economic empowerment (EE) intervention on viral suppression in five districuts in Uganda. In total, 39 accredited health care clinics from study districts with existing procedures tailored to adolescent adherence were eligible to participate in the trial. We used data from 288 youth with detectable HIV viral loads (VL) at baseline (158 -intervention group from 20 clinics, 130 -non-intervention group from 19 clinics). The primary end point was undetectable plasma HIV RNA levels, defined as \u3c 40 copies/ml. We used Kaplan-Meier (KM) analysis and Cox proportional hazard models to estimate intervention effects. FINDINGS: The Kaplan-Meier (KM) analysis indicated that an incidence of undetectable VL (0.254) was significantly higher in the intervention condition compared to 0.173 (in non-intervention arm) translated into incidence rate ratio of 1.468 (CI: 1.064-2.038), p = 0.008. Cox regression results showed that along with the family-based EE intervention (adj. HR = 1.446, CI: 1.073-1.949, p = 0.015), higher number of medications per day had significant positive effects on the viral suppression (adj.HR = 1.852, CI: 1.275-2.690, p = 0.001). INTERPRETATION: A family economic empowerment intervention improved treatment success for ALWHIV in Uganda. Analyses of cost effectiveness and scalability are needed to advance incorporation of this intervention into routine practice in low and middle-income countries

    Use of injectable hormonal contraception and women’s risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, Uganda

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    Background The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but fi ndings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women. Methods In this prospective study, we enrolled HIV-negative and HSV2-negative women aged 15–49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984. Findings Between Aug 11, 2003, and July 6, 2006, we enrolled 682 women in this study. We noted HSV2 seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using DMPA (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 (95% CI 1·09–4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49–26·3; p=0·012). Interpretation Consistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These fi ndings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly eff ective contraceptive methods is needed for women, particularly in sub-Saharan Africa

    Estimation of cause-specific mortality in Rakai, Uganda, using verbal autopsy 1999-2019

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    BackgroundThere are scant data on the causes of adult deaths in sub-Saharan Africa. We estimated the level and trends in adult mortality, overall and by different causes, in rural Rakai, Uganda, by age, sex, and HIV status.ObjectivesTo estimate and analyse adult cause-specific mortality trends in Rakai, Uganda.MethodologyMortality information by cause, age, sex, and HIV status was recorded in the Rakai Community Cohort study using verbal autopsy interviews, HIV serosurveys, and residency data. We estimated the average number of years lived in adulthood. Using demographic decomposition methods, we estimated the contribution of each cause of death to adult mortality based on the average number of years lived in adulthood.ResultsBetween 1999 and 2019, 63082 adults (15–60 years) were censused, with 1670 deaths registered. Of these, 1656 (99.2%) had completed cause of death data from verbal autopsy. The crude adult death rate was 5.60 (95% confidence interval (CI): 5.33–5.87) per 1000 person-years of observation (pyo). The crude death rate decreased from 11.41 (95% CI: 10.61–12.28) to 3.27 (95% CI: 2.89–3.68) per 1000 pyo between 1999–2004 and 2015–2019. The average number of years lived in adulthood increased in people living with HIV and decreased in HIV-negative individuals between 2000 and 2019. Communicable diseases, primarily HIV and Malaria, had the biggest decreases, which improved the average number of years lived by approximately extra 12 years of life in females and 6 years in males. There were increases in deaths due to non-communicable diseases and external causes, which reduced the average number of years lived in adulthood by 2.0 years and 1.5 years in females and males, respectively.ConclusionThere has been a significant decline in overall mortality from 1999 to 2019, with the greatest decline seen in people living with HIV since the availability of antiretroviral therapy in 2004. By 2020, the predominant causes of death among females were non-communicable diseases, with external causes of death dominating in males
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