Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings

AIDS. 2012 Jul 17;26(11):1345-54. doi: 10.1097/QAD.0b013e328353b066.

Abstract

Objective: To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs).

Design: An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000 copies/ml.

Methods: Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100 mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r.

Results: Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400 copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40 copies/ml and 30 had levels 40-200 copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400 copies/ml.

Conclusion: In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / epidemiology
  • Acquired Immunodeficiency Syndrome / immunology
  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adult
  • Africa / epidemiology
  • Anti-HIV Agents / administration & dosage*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Emtricitabine
  • Female
  • Health Resources / supply & distribution
  • Humans
  • India / epidemiology
  • Lopinavir / administration & dosage*
  • Male
  • Medication Adherence
  • Middle Aged
  • Mutation
  • Organophosphonates / administration & dosage*
  • Patient Selection
  • Pilot Projects
  • RNA, Viral / drug effects*
  • RNA, Viral / immunology
  • Reverse Transcriptase Inhibitors / adverse effects
  • Ritonavir / administration & dosage*
  • Surveys and Questionnaires
  • Tenofovir
  • Thailand / epidemiology
  • Treatment Failure
  • Viral Load

Substances

  • Anti-HIV Agents
  • Organophosphonates
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Deoxycytidine
  • Lopinavir
  • Tenofovir
  • Emtricitabine
  • Adenine
  • Ritonavir