Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

Abstract
The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial. Human immunodeficiency virus (HIV)–infected, ART-eligible children were enrolled into 2 cohorts based on prior NVP exposure and randomized to NVP- or LPV/r-based ART. The data safety monitoring board recommended unblinding results in both cohorts due to superiority of LPV/r for the primary endpoint: stopping randomized treatment, virologic failure (VF), or death by 6 months. Participants were offered a switch in regimens (if on NVP) and continued observational follow-up. We compared time to VF or death, death, and CD4% and growth changes using intention-to-treat analyses. Additionally, inverse probability weights were used to account for treatment switching and censoring. As of September 2014, 329 of the 451 (73%) enrolled participants were still in follow-up (median, 5.3 years; interquartile range [IQR], 4.3–6.4), with 52% on NVP and 88% on LPV/r as originally randomized. NVP arm participants had significantly higher risk of VF or death (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.37–2.65) but not death alone (aHR, 1.65; 95% CI, .72–3.76) compared with participants randomized to LPV/r. Mean CD4% was significantly higher in the NVP arm up to 1 year after ART initiation, but not beyond. Mean weight-for-age z scores were marginally higher in the NVP arm, but height-for-age z scores did not differ. Similar trends were observed in sensitivity analyses. These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children.
Description
Keywords
HIV/AIDS, Antiretroviral therapy, Pediatrics, Long-term follow-up
Citation
Barlow-Mosha, L., Angelidou, K., Lindsey, J., Archary, M., Cotton, M., Dittmer, S., ... & Chi, B. H. (2016). Nevirapine-versus lopinavir/ritonavir-based antiretroviral therapy in HIV-infected infants and young children: long-term follow-up of the IMPAACT P1060 randomized trial. Clinical Infectious Diseases, 63(8), 1113-1121.https://doi.org/10.1093/cid/ciw488