Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda.

BACKGROUND: With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). METHODS: We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. RESULTS: Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥ 70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36-7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count < 250 cells/µl (AOR 2.80, 95% CI: 1.08-7.29) and viral load ≥ 100,000 copies/ml (AOR 2.48, 95% CI: 1.00-6.14). CONCLUSION: Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.

HIV incidence and recent injections among adults in rural southwestern Uganda.

Thirty-six incident HIV cases were matched for age, sex and time period with 36 controls to examine associations with recent injections. A significant association between HIV incidence and a history of injections was detected that was not reduced after adjusting for available sexual behaviour variables. This association could either be the result of injections causing HIV infection or, more likely, injections for seroconversion illnesses or other consequences of unsafe sex.

HIV and mortality of mothers and children: evidence from cohort studies in Uganda, Tanzania, and Malawi.

BACKGROUND: The steady decline in child mortality observed in most African countries through the 1960s, 1970s, and 1980s has stalled in many countries in the 1990s because of the AIDS epidemic. However, the census and household survey data that generally are used to produce estimates of child mortality do not permit precise measures of the adverse effect of HIV on child mortality. METHODS: To calculate excess risks of child mortality as the result of maternal HIV status, we used pooled data from 3 longitudinal community-based studies that classified births by the mother's HIV status. We also estimated excess risks of child death caused by increased mortality among mothers. The joint effects of maternal HIV status and maternal survival were quantified using multivariate techniques in a survival analysis. RESULTS: Our analysis shows that the excess risk of death associated with having an HIV-positive mother is 2.9 (95% confidence interval = 2.3-3.6), and this effect lasts throughout childhood. The excess risk associated with a maternal death is 3.9 (2.8-5.5) in the 2-year period centered on the mother's death, with children of both infected and uninfected mothers experiencing higher mortality risks at this time. CONCLUSION: HIV impacts on child mortality directly through transmission of the virus to newborns by infected mothers and indirectly through higher child mortality rates associated with a maternal death.

Evaluation of a home-based voluntary counselling and testing intervention in rural Uganda.

BACKGROUND: Uptake of HIV test results from an annual serosurvey of a population study cohort in rural southwestern Uganda had never exceeded 10% in any given year since inception in 1989. An intervention offering counselling and HIV results at home was conducted in four study villages following the 2001 serosurvey round, and followed by a qualitative evaluation exploring nature of demand and barriers to knowing HIV status. METHODS: Data from annual serosurveys and counsellor records are analyzed to estimate the impact of the intervention on uptake of HIV test results. Textual data are analyzed from 21 focus group discussions among counsellors, and men and women who had received HIV test results, requested but not yet received, and never requested; and 34 in-depth interviews equally divided among those who had received test results either from counselling offices and homes. RESULTS: Offering HIV results at home significantly increased uptake of results from 10 to 37% for all adults aged 15 (p<0.001), and 46% of those age 25 to 54. Previous male advantage in uptake of test results was effectively eliminated. Focus group discussions and in-depth interviews highlight substantial non-monetary costs of getting HIV results from high-visibility public facilities prior to intervention. Inconvenience, fear of stigmatization, and emotional vulnerability of receiving results from public facilities were the most common explanations for the relative popularity of home-based voluntary counselling and testing (VCT). It is seen as less appropriate for youth and couples with conflicting attitudes toward testing. CONCLUSIONS: Home delivery of results revealed significantly higher demand to know HIV status than stubbornly low uptake figures from the past would suggest. Integrating VCT into other services, locating testing centres in less visible surroundings, or directly confronting stigma surrounding testing may be less expensive ways to reproduce increased uptake with home VCT.

Child survival in relation to mother's HIV infection and survival: evidence from a Ugandan cohort study.

OBJECTIVE: To analyse the contribution of maternal survival and HIV status to child (under-5 years) mortality in a rural population cohort in South-west Uganda. METHODS: Approximately 10 000 people residing in 15 neighbouring villages were followed between 1989 and 2000 using annual censuses and serological surveys to collect data on births, deaths, and adult HIV serostatus. Mother-child records were linked, child mortality risks (per 1000 births) and hazard ratios (HRs) for child mortality according to maternal HIV serostatus were computed, allowing for time-varying covariates. RESULTS: A total of 3727 children were born, of whom 415 died during 14 110 child years of follow-up. Mother's HIV status at birth was ascertained unambiguously for 3004 children, of whom 218 were born to HIV-positive mothers. Infant mortality risk was higher for HIV seropositive than seronegative mothers (225 versus 53) as was child mortality risk (313 versus 114). Child mortality risk was also higher for mothers who died (571) than for surviving mothers (128). After controlling for child's age and sex, independent predictors of mortality in children were: mother's terminal illness or death (HR = 3.8); mother being HIV positive (HR = 3.2); child being a twin (HR = 2.0); teenage motherhood (HR = 1.7) and maternal absence (HR = 1.7). CONCLUSION: Maternal survival and HIV status are strong predictors of child survival. The higher mortality in HIV-infected women compounds mortality risks for their children, regardless of children's HIV status. Programmes aimed at the welfare of children should take into account the independent effect of mothers' HIV and vital status.