Immunologic Response to Highly Active Antiretroviral Therapy and Mortality Reduction in a Cohort of Human Immunodeficiency Virus–Positive Persons in Mozambique

Since February 2002, the Drug Resources Enhancement against AIDS and Malnutrition Program has provided highly active antiretroviral therapy (HAART) and immunologic and virologic monitoring free of charge. We conducted a cohort study of persons infected with human immunodeficiency virus in Mozambique. Only persons treated with HAART with available CD4 cell counts at baseline and ≥ 1 CD4 cell count after HAART were included. Survival analysis was applied to evaluate the prognostic value of CD4 cell counts measured at three months. Possible confounders were considered. A total of 753 persons who started HAART included; 59% were females. Median age was 34 years (range = 16–67 years), and the median CD4 cell count at baseline was 172 cells/mm3 (interquartile range = 87–261 cells/mm3, range = 0–1,322 cells/mm3). Overall, 105 persons (14%) died. Of these persons 54 (51%) developed AIDS before they died; 25 (3%) died during the first three months. After three months of therapy, the individual median CD4 cell count change from the baseline value was +101 cells/mm3 (interquartile range = +27 to +187 cells/mm3, range = –723 to +310 cells/mm3). A median CD4 increment of 100 cells/mm3 in three months was associated with a mortality reduction of 50% compared with an increase of < 50 cells (relative hazard of death adjusted for baseline CD4 cell count = 0.54, 95% confidence interval = 0.30–0.95). A good initial response to HAART was associated with a significant reduction of mortality. This finding supports the effectiveness of HAART in resource-poor settings

Incidence and Predictors of Death, Retention, and Switch to Second-Line Regimens in Antiretroviral-Treated Patients in Sub-Saharan African Sites with Comprehensive Monitoring Availability

Background. Antiretroviral treatment programs in sub-Saharan Africa have high rates of early mortality and loss to follow-up. Switching to second-line regimens is often delayed because of limited access to laboratory monitoring. Methods. Retrospective analysis was performed of a cohort of adults who initiated a standard first-line antiretroviral treatment at 5 public sector sites in 3 African countries. Monitoring included routine CD4 cell counts, human immunodeficiency virus RNA measures, and records of whether appointments were kept. Incidence and predictors of death, loss to follow-up, and switch to second-line regimens were analyzed by time-to-event approaches. Results. A total of 3749 patients were analyzed; at baseline, 37.1% were classified as having World Health Organization disease stage 3 or 4, and the median CD4 cell count was 192 cells/μL. First-line regimens were nevirapine based in 96.5% of patients; 17.7% of patients attended <95% of their drug pickup appointments. During 4545 person-years of follow-up, mortality was 8.6 deaths per 100 person-years and was predicted by lower baseline CD4 cell count, lower hemoglobin level, and lower body mass index (calculated as weight in kilograms divided by the square of height in meters); more-advanced clinical stage of infection; male sex; and more missed drug pickup appointments. Dropouts (which accrued at a rate of 2.1 dropouts per 100 person-years) were predicted by a lower body mass index, more missed visits and missed drug pickup appointments, and later calendar year. Incidence of switches to second-line regimens was 4.9 per 100 person-years; increased hazards were observed with lower CD4 cell count and earlier calendar year at baseline. In patients who switched, virological failure was predicted by combined clinical and CD4 criteria with 74% sensitivity and 30% specificity. Conclusions. In an antiretroviral treatment program employing comprehensive monitoring, the probability of switching to second-line therapy was limited. Regular pickup of medication was a predictor of survival and was also strongly predictive of patient retention