In a randomized trial comparing nevirapine (NVP)- versus lopinavir/ritonavir (LPV/r)– based antiretroviral therapy (ART) in HIV-infected children (primary endpoint discontinuation of study treatment for any reason or virologic failure (VF) by week 24) aged two months to three years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates.
Efficacy was assessed by time to ART discontinuation or VF, VF/death, and death; safety by time to ART discontinuation due to a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height WHO z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates.
Over a median follow-up of 48 (PrNVP) and 72 (No PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r – based ART was superior to NVP-based ART for efficacy and safety outcomes but those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pre-treatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pre-treatment CD4% with shorter time to ART discontinuation due to a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥3 adverse event.
Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breastfeeding, sex, HIV-1 subtype, age, pre-treatment CD4%, HIV-1 RNA or WHO disease stage. This finding should be considered when selecting an ART regimen for young children.