Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy

J Antimicrob Chemother. 2005 Dec;56(6):1081-6. doi: 10.1093/jac/dki356. Epub 2005 Sep 29.

Abstract

Background: Lopinavir/ritonavir is a protease inhibitor (PI) that has shown great effectiveness as salvage therapy in PI-experienced HIV-infected children.

Objectives: To study whether mutations in the HIV-1 protease gene can reliably predict virological responses to salvage therapy with lopinavir/ritonavir in HIV-infected children.

Patients and methods: We carried out a prospective study in 56 HIV-infected children. PI-associated resistance mutations were determined by genotypic testing and were scored according to the IAS-USA guidelines 2005.

Results: Children with a 'lopinavir mutation score' (LMS) > or = 6 had a negative association for achieving viral load (VL) control [undetectable viral load (uVL) < or = 400 copies/mL] and maintaining uVL for at least 6 months. Moreover, children with protease-associated mutations (PRAMs) > or = 2 had a negative association for achieving VL control but not for maintaining uVL for at least 6 months. The relative proportion (RP) to uVL was 0.32 (CI95%: 0.16; 0.33; P = 0.002) in children with I54V (46% of total) and 0.48 (CI95%: 0.24; 0.97; P = 0.041) in children with V82A/F (52% of total). Children with I54V and V82A/F had higher prevalence of lopinavir-associated resistance mutations and showed RP of 0.36 (CI95%: 0.17; 0.76; P = 0.007) for achieving uVL.

Conclusions: LMS and PRAMs in HIV-infected children were associated with virological failure in pre-treated HIV-infected children on salvage therapy with lopinavir/ritonavir. Moreover, I54V and V82A/F led to the poorest virological response.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Child
  • Child, Preschool
  • Drug Resistance, Viral / genetics*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease / genetics*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Humans
  • Infant
  • Lopinavir
  • Male
  • Mutation*
  • Prognosis
  • Prospective Studies
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / pharmacology
  • Pyrimidinones / therapeutic use*
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacology
  • Ritonavir / therapeutic use*
  • Salvage Therapy
  • Viral Load

Substances

  • Anti-HIV Agents
  • Pyrimidinones
  • Lopinavir
  • HIV Protease
  • Ritonavir