Time to treatment disruption in children with HIV-1 randomized to initial antiretroviral therapy with protease inhibitors versus non-nucleoside reverse transcriptase inhibitors

PLoS One. 2020 Nov 23;15(11):e0242405. doi: 10.1371/journal.pone.0242405. eCollection 2020.

Abstract

Background: Choice of initial antiretroviral therapy regimen may help children with HIV maintain optimal, continuous therapy. We assessed treatment-naïve children for differences in time to treatment disruption across randomly-assigned protease inhibitor versus non-nucleoside reverse transcriptase inhibitor-based initial antiretroviral therapy.

Methods: We performed a secondary analysis of a multicenter phase 2/3, randomized, open-label trial in Europe, North and South America from 2002 to 2009. Children aged 31 days to <18 years, who were living with HIV-1 and treatment-naive, were randomized to antiretroviral therapy with two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Time to first documented treatment disruption to any component of antiretroviral therapy, derived from treatment records and adherence questionnaires, was analyzed using Kaplan-Meier estimators and Cox proportional hazards models.

Results: The modified intention-to-treat analysis included 263 participants. Seventy-two percent (n = 190) of participants experienced at least one treatment disruption during study. At 4 years, treatment disruption probabilities were 70% (protease inhibitor) vs. 63% (non-nucleoside reverse transcriptase inhibitor). The unadjusted hazard ratio (HR) for treatment disruptions comparing protease inhibitor vs. non-nucleoside reverse transcriptase inhibitor-based regimens was 1.19, 95% confidence interval [CI] 0.88-1.61 (adjusted HR 1.24, 95% CI 0.91-1.68). By study end, treatment disruption probabilities converged (protease inhibitor 81%, non-nucleoside reverse transcriptase inhibitor 84%) with unadjusted HR 1.11, 95% CI 0.84-1.48 (adjusted HR 1.13, 95% CI 0.84-1.50). Reported reasons for treatment disruptions suggested that participants on protease inhibitors experienced greater tolerability problems.

Conclusions: Children had similar time to treatment disruption for initial protease inhibitor and non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy, despite greater reported tolerability problems with protease inhibitor regimens. Initial pediatric antiretroviral therapy with either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor may be acceptable for maintaining optimal, continuous therapy.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / methods
  • Antiretroviral Therapy, Highly Active / trends
  • CD4 Lymphocyte Count / methods
  • Child
  • Child, Preschool
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / therapeutic use
  • HIV Seropositivity / drug therapy
  • HIV-1 / pathogenicity
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Patient Compliance / statistics & numerical data*
  • Proportional Hazards Models
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Time-to-Treatment / statistics & numerical data*
  • Time-to-Treatment / trends
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors