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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children.

Clinical trials registration: NCT00307151.

Keywords: HIV/AIDS; antiretroviral therapy; long-term follow-up; pediatrics.

Figure 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram of participant flow through the different stages of the International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1060 trial. Abbreviations: 3TC, lamivudine; DSMB, data safety monitoring board; LPV/r, lopinavir/ritonavir; NVP, nevirapine; ZDV, zidovudine.

Figure 2.

Kaplan–Meier analysis comparing primary outcomes in the International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1060 trial, including death only (A), virologic failure or death (B), and virologic failure or death, stratified by baseline viremia level (C). The figures included at the bottom of each graph represent the number of participants at risk at each time point. Abbreviations: LPV/r, lopinavir/ritonavir; NVP, nevirapine.

Figure 3.

Trends in specific treatment outcomes (mean, 95% confidence intervals) over time for the nevirapine (NVP) and lopinavir/ritonavir (LPV/r) arms of the International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1060 trial, CD4 percentage (A and B), height-for-age z scores (C and D), and weight-for-age z scores (E and F). The figures included at the bottom of each graph represent the number of participants with available data at each time point.