Background:  Although access to HAART is increasing in developing countries, there are few data on the predictors of immunological response in previously untreated adults in such settings.

Methods:   DART (Development of Anti-Retroviral Therapy in Africa) is an open-label, randomized trial comparing 2 therapeutic approaches to be tested in resource-poor settings:  clinical monitoring only vs laboratory plus clinical monitoring, and structured treatment interruptions vs continuous therapy in patients who achieve CD4 cell counts >200 cells/mL after 24 or 48 weeks of continuous ART. Subjects were 3000 symptomatic ART-naive adults from 3 sites (2 in Uganda, 1 in Zimbabwe) who had CD4 <200 cells/mL, received 3-drug ART, and followed for 5 years. We used logistic regression models to investigate the association between CD4 response (increase >100 cells/mL, or to >200 cells/mL) 24 weeks after HAART initiation and sex, age, disease stage, weight, and CD4 count at HAART initiation. This was a global analysis, not broken down by randomized group.

Results:  Until 3 October 2003, 1193 adults had been randomized (67% women; median age 37 years (IQR 33 to43); 27% WHO stage 4, median CD4 84 (33% <50 cells/mL). All received ZDV/3TC/TDF as first line ART. Only 11 (1%) of the enrolled patients have thus far switched their treatment (all switching ZDV to d4T for toxicity). As expected, baseline CD4 was significantly lower in patients with later stage disease, and in men compared to women (both p <0.001). 132 patients have reached 24 weeks, of whom 43, 30, 44, and 15 initiated HAART with CD4 0-49, 50-99, 100-149, and 150-199 cells/mL, respectively. 65 (49%) adults have increased CD4 by at least 100 cells/mL at 24 weeks (median increase 98, IQR 44-152) and 58 (44%) have achieved a CD4 of >200 cells/mL. Among the 43 patients initiating HAART with CD4 <50 cells/mL, 24 (56%) had CD4 increases >100 cells/mL and 9 (21%) had CD4 >200 by week 24; among those with CD4 50 to 199 at HAART (n = 89), CD4 increased by >100 cells in 41 (46%) and 49 (55%) had CD4 >200 by week 24. We found no evidence to suggest that the chance of CD4 increases >100 cells/mL were influenced by pre-HAART CD4 (OR = 0.86, p = 0.40), or the other factors described above.

Conclusions:  Achieving CD4 increases of >100 cells after 24 weeks on HAART in Africa appears to occur regardless of pre-HAART factors including low baseline CD4. The CD4 increases observed are in line with those obtained in industrialised countries.

Keywords: Immunological response; HAART; ART-naive