Virologic failure among children taking lopinavir/ritonavir-containing first-line antiretroviral therapy in South Africa

Pediatr Infect Dis J. 2015 Feb;34(2):175-9. doi: 10.1097/INF.0000000000000544.

Abstract

Objective: To report the outcomes, clinical management decisions and results of resistance testing among a group of children who developed virologic failure on first-line lopinavir/ritonavir (LPV/r)-based therapy from a large cohort of antiretroviral therapy-treated children in Soweto.

Design: Historical cohort study.

Methods: Children with virologic failure were identified from a group of 1692 children <3 years who had initiated first-line LPV/r-containing therapy since 2000 up to the end November 2011. Genotyping was conducted in some children, and outcomes, management decisions and resistance results were described.

Results: A total of 152 children with virologic failure on first-line LPV/r-containing antiretroviral therapy were included. Resistance testing was performed in 75/152 (49%), and apart from a younger age (11.1 vs. 15.1 months, P = 0.04), the children with versus those without resistance testing were similar for baseline characteristics (weight, CD4, viral load and time to failure). Genotyping revealed that 8/75 (10.7%) had significant LPV/r-associated resistance mutations, including 2 with intermediate darunavir resistance. Among 63/75 (84%) children remaining on LPV/r-based therapy, 32/63 (51%) achieved virologic suppression, and 2 of these children with significant LPV mutations. In accordance with the local guidelines at the time, 12/152 (8%) children were switched to non-nucleoside reverse-transcriptase inhibitors-based therapy. Of these, 4/12 (33%) resuppressed, and the rest did not achieve virologic suppression including the 2 with lopinavir mutations.

Conclusions: Virologic failure of LPV/r-containing first-line regimens is associated with accumulation of LPV/r mutations in children. The implications are unclear, and surveillance at selected sites is warranted for long-term virologic outcomes and development of resistance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Child, Preschool
  • Cohort Studies
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • HIV / genetics
  • HIV / isolation & purification
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Infant
  • Lopinavir / therapeutic use*
  • Male
  • Mutation, Missense
  • Ritonavir / therapeutic use*
  • South Africa
  • Treatment Failure
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • Lopinavir
  • Ritonavir