Highly Active Antiretroviral Therapy (HAART) as a Strategy for Reduction of HIV-1 Transmission in Sub-Saharan Africa: Survival and Virus Load Parameters from the Drug Resource Enhancement Against AIDS and Malnutrition

Background: The concept of universal antiretroviral use as a strategy for reduction of new cases of HIV infection has been evaluated in mathematical models as a potential approach to curtailing the Sub-Saharan African epidemic. In order to further substantiate such models, additional strategic parameters based on robust patient data should be considered, including survival of HIV-infected populations under HAART and subject infectivity as determined by HIV RNA levels. Methods: A retrospective cohort study was conducted in a population of patients enrolled in DREAMcenters throughout sub-Saharan Africa in order to determine survival under HAART. Cox regression analysis was performed evaluating parameters associated with survival such as CD4 cell count, viral load, body mass index (BMI) and hemoglobin (HB) levels. DREAM criteria for HAART initiation included (1) WHO stage 3-4 regardless of CD4 cell value (2) <350 CD4 cells if asymptomatic (3) virus load >100,000 copies in any subject. Virus load response to HAART was assessed in a subset of patients. Results: Adult non-pregnant patients who accessed DREAM centers from 1/2002 to 7/2009 were evaluated. A total of 34,295 patients (22,249 females/12,041 males) were included. Median age was 34 years (IQR:29-42) and median observation time 476 days (IQR:206 –950). Baseline median viral load, CD4 cell counts, HB and BMI values were 4.4 (IQR:3.6-5.0), 243 (IQR:109-416), 10.8 (IQR:9.2-12.4), and 20.3 (IQR:18.3-22.7).Over time 23,795 patients initiated HAART. Cox survival analysis (adjusted for Viral Load and HB) according to CD4 cell strata was performed. The relative risk of death in the lowest CD4 stratum (<100) versus the highest stratum (>500) was 3.3 [2.7 –4.1]. Survival estimates at >7 years of HAART ranged from 50% to 95% according to baseline CD4 cell count and HB levels. In a subset of 13,405 subjects who received HAART for >6 months with at least 2 virus load measures available, 55.9% achieved < 50 copies/ml and an additional 19.7% achieved levels < 400 copies/ml (75.6% total). Final median virus load value was 58 (IQ: 0 –2000). Conclusions: Contrary to more conservative estimates used in mathematical modeling studies, patients in our cohort demonstrated a significant survival benefit even within the lowest CD4 cell stratum. Patients on HAART had low potential infectivity as measured by plasma virus load. Cohort data from African patients can contribute to the further refinement of predictive models