Background:  There are few data on virological and immunological outcomes in infants starting early ART in sub-Saharan Africa.

Methods:  Infants aged 6 to 12 weeks with CD4% ≥25% (Part A, n = 411) and CD4<25% (Part B, n = 40) enrolled in the CHER trial commenced LPV/r, zidovudine, lamivudine either immediately or upon clinical/immunological progression. Virological response was defined as HIV RNA <400 copies/mL and immunological response as CD4% increase ≥10% from pre-ART level, at 24 and 40 (or 48 if missing at 40) weeks after ART initiation. The association between selected factors including age at initiation and response was assessed, ignoring randomized arm, using logistic regression.

Results:  By end April 2009, 386 children had started ART and had data for ≥1 outcome. Median age at initiation was 8.4 (IQR 7.1 to 11.2) weeks (79% treated by 12 weeks), weight-for-age z-score -0.8 (-1.6 to 0.0) and CD4% 32% (24 to 38%). HIV-1 RNA was <400 copies/mL in 71% of children at 24 weeks after initiation and 77% at 40/48 weeks. Eight percent rebounded to >400copies/ml at 40/48 weeks after suppression at 24 weeks. Virological response was not associated with age at initiation (OR at 24 weeks 1.04 per 4 weeks increase, 95%CI 0.95 to 1.14, P =0.39), CD4%, weight-for-age z-score, HIV-1 RNA or gender. However, only 5/15 (33%) children with active TB diagnosed before or within 1 month after initiation on concurrent TB therapy achieved HIV RNA <400 copies/mL at 24 weeks compared to 241/334 (72%) of the remaining children (OR = 0.17, 0.06 to 0.55, P =0.003); the effect of baseline TB weakened slightly by 40/48 weeks (OR = 0.32, 0.10 to 0.99, P =0.05). Median change in CD4% from pre-ART level was similar at 24 weeks (7%, IQR 1% to 13%) and 40/48 weeks (7%, -1% to 13%); corresponding proportions with CD4% increase ≥10% were 33% and 32%, respectively. As expected, CD4% increase ≥10% was more likely with lower CD4% at initiation, this being the only predictor of immunological response at both time-points.

Conclusions:  Virological response was satisfactory in this large cohort of infants initiating lopinavir-based ART in South Africa, and similar to rates reported in infants from well-resourced settings. Younger age at initiation was not associated with improved response but most started ART in the first few months of life. Although numbers are small, active TB diagnosed before or around the time of ART initiation was linked to short-term virological failure. Studies of resistance are ongoing.