Predicting trends in HIV-1 sexual transmission in sub-Saharan Africa through the Drug Resource Enhancement Against AIDS and Malnutrition model: antiretrovirals for 5 reduction of population infectivity, incidence and prevalence at the district level.

BACKGROUND: The use of antiretrovirals to reduce the incidence of human immunodeficiency virus (HIV) infection has been evaluated in mathematical models as potential strategies for curtailing the epidemic. Cohort data from the Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Program was used to generate a realistic model for the HIV epidemic in sub-Saharan Africa. METHODS: Two combined stochastic models were developed: patient and epidemic models. Models were combined using virus load as a parameter of infectivity. DREAM data that assessed patient care in Mozambique and Malawi were used to generate measures of infectivity, survival, and adherence. The Markov chain prediction model was used for the analysis of disease progression in treated and untreated patients. A partnership model was used to assess the probability that an infected individual would transmit HIV. RESULTS: Data from 26565 patients followed up from January 2002 through July 2009 were analyzed with the model; 63% of patients were female, the median age was 35 years, and the median observation time was 25 months. In the model, a 5-fold reduction in infectivity (from 1.6% to 0.3%) occurred within 3 years when triple ART was used. The annual incidence of HIV infection declined from 7% to 2% in 2 years, and the prevalence was halved, from 12% to 6%, in 11 years. Mortality in HIV-infected individuals declined by 50% in 5 years. A cost analysis demonstrated economic efficiency after 4 years. CONCLUSIONS: Our model, based on patient data, supports the hypothesis that treatment of all infected individuals translates into a drastic reduction in incident HIV infections. A targeted implementation strategy with massive population coverage is feasible in sub-Saharan Africa.

Limited risk of drug resistance after discontinuation of antiretroviral prophylaxis for the prevention of breastfeeding transmission of HIV.

We evaluated 70 HIV-infected pregnant women with CD4⁺ cell count >350 cells per cubic millimeter who received zidovudine, lamivudine, and nevirapine from week 25 of gestation until 6 months after delivery and a 3-week tail of zidovudine and lamivudine at the moment of drug discontinuation. Forty days after the interruption of all drugs resistance mutations were present in 5 of 70 (7.1%) women. Two of them had the same mutation archived in baseline HIV DNA. The other 3 women had, at least once, detectable viral load and presence of mutations during treatment. Overall, the risk of developing resistance mutations in compliant women was low.

Extended antenatal use of triple antiretroviral therapy for prevention of mother-to-child transmission of HIV-1 correlates with favorable pregnancy outcomes.

OBJECTIVE: To evaluate pregnancy outcomes in a cohort of HIV-infected women receiving triple antiretroviral therapy (ART) for prevention of mother-to-child-transmission. METHODS: A retrospective cohort study with review of records of 3273 HIV-positive women receiving prenatal care in Malawi and Mozambique from July 2005 to December 2009 was conducted in Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) centers. Patients were offered nevirapine-based triple ART initiated in pregnancy until 6 months postpartum. Main outcome measures were maternal mortality, abortion/stillbirth, prematurity, and low birth weight. RESULTS: Maternal mortality was 1.2% (42/3273): 7.4% in 68 women with no antenatal ART and 0.7% in 1370 with at least 90 days of antenatal ART [P < 0.001; odds ratio (OR) 0.29 (95% confidence interval [CI] 0.14-0.96]. Abortion/stillbirth was 5.2% (169/3273): 26.5% in 68 women with no ART and 5.0% in 1370 women with at least 90 days of antenatal ART [P < 0.001; OR 0.39 (95% CI 0.27-0.57)]. Prematurity was 19.1%: 70% in 10 women with no antenatal ART and 8.5% in 1330 women with at least 90 days of antenatal ART [P < 0.001; OR 0.15 (95% CI 0.14-0.19)]. Low birth weight was 11.5% (57/496) and not associated with ART duration. The protective effect of antenatal ART against mortality, fetal demise, and prematurity was independent of CD4 strata. Multivariate analysis for BMI, CD4 cell count, virus load, days in care, predelivery length of ART, and hemoglobin demonstrated an independent association between predelivery length of ART and CD4 with maternal mortality, abortion/stillbirth, and prematurity. ART toxicities were infrequent (5.2%). CONCLUSION: Antenatal triple ART reduces adverse pregnancy outcomes in HIV-infected women.

Extended antenatal antiretroviral use correlates with improved infant outcomes throughout the first year of life.

OBJECTIVES: To evaluate the effect of extended antenatal triple antiretroviral therapy (ART) on infant outcomes. DESIGN: Retrospective cohort study using pooled data from health clinics in Malawi and Mozambique from July 2005 to December 2009. METHODS: Computerized records of 3273 HIV-infected pregnant women accessing Drug Resource Enhancement Against AIDS and Malnutrition centers were reviewed. ART regimens consisted of nevirapine-based HAART as of 14-25 weeks gestation until 6 months postpartum. Infant infection was determined at 1, 6 and 12 months of age by branched DNA. RESULTS: A total of 3071 pregnancies resulted in 3148 live births. Lost to follow-up, infant deaths and HIV-1 infection rates at 1 and 12 months were 1.3 and 11.5, 0.8 and 6.7 and 0.8 and 2.0, respectively. Infant HIV-1-free survival at 12 months was 92.5%. Mother-to-child transmission and/or infant deaths correlated with length of maternal antenatal ART by multivariate analysis at 1, 6 and 12 months: 14% in women with more than 30 days of triple antenatal ART and 6.9% in mothers receiving at least 90 days of antenatal ART, P = 0.001. Fifty percent of 54 episodes of transmission occurred in women with higher CD4 cell counts (>350 cells/µl). Infant mortality was 67/1000, lower than background rates (78-100/1000). Growth failure (weight-for-age Z score <-2) was present in 8% of infants around birth, 6% at 6 months, 23% at 12 months (lower than country-specific rates). CONCLUSION: Extended antenatal ART is protective against adverse infant outcomes up to 12 months of age even in children born to mothers with higher CD4 cell counts.