Antiretroviral therapy and efficacy after virologic failure on first-line boosted protease inhibitor regimens

Clin Infect Dis. 2014 Sep 15;59(6):888-96. doi: 10.1093/cid/ciu367. Epub 2014 May 19.

Abstract

Background: Virologic failure (VF) on a first-line ritonavir-boosted protease inhibitor (PI/r) regimen is associated with low rates of resistance, but optimal management after failure is unknown.

Methods: The analysis included participants in randomized trials who experienced VF on a first-line regimen of PI/r plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) and had at least 24 weeks of follow-up after VF. Antiretroviral management and virologic suppression (human immunodeficiency virus type 1 [HIV-1] RNA <400 copies/mL) after VF were assessed.

Results: Of 209 participants, only 1 participant had major PI-associated treatment-emergent mutations at first-line VF. The most common treatment approach after VF (66%) was to continue the same regimen. The virologic suppression rate 24 weeks after VF was 64% for these participants, compared with 72% for those who changed regimens (P = .19). Participants remaining on the same regimen had lower NRTI resistance rates (11% vs 30%; P = .003) and higher CD4(+) cell counts (median, 275 vs 213 cells/µL; P = .005) at VF than those who changed. Among participants remaining on their first-line regimen, factors at or before VF significantly associated with subsequent virologic suppression were achieving HIV-1 RNA <400 copies/mL before VF (odds ratio [OR], 3.39 [95% confidence interval {CI}, 1.32-8.73]) and lower HIV-1 RNA at VF (OR for <10 000 vs ≥10 000 copies/mL, 3.35 [95% CI, 1.40-8.01]). Better adherence after VF was also associated with subsequent suppression (OR for <100% vs 100%, 0.38 [95% CI, .15-.97]). For participants who changed regimens, achieving HIV-1 RNA <400 copies/mL before VF also predicted subsequent suppression.

Conclusions: For participants failing first-line PI/r with no or limited drug resistance, remaining on the same regimen is a reasonable approach. Improving adherence is important to subsequent treatment success.

Keywords: antiretroviral therapy; first-line; protease inhibitor; virologic failure.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1*
  • Humans
  • Male
  • Randomized Controlled Trials as Topic
  • Retreatment
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Treatment Outcome
  • Viral Load

Substances

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