Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview

J Acquir Immune Defic Syndr. 2006 Mar;41(3):323-31. doi: 10.1097/01.qai.0000197070.69859.f3.

Abstract

Objective: To identify optimal first-line therapies based on the rate of virologic success (VS) and the preservation of future treatment options in antiretroviral therapy (ART)-naive subjects.

Design: Systematic overview of genotypic resistance mutations from clinical trials of combination ART.

Methods: Various sources were searched for studies in ART-naive subjects providing virologic response rates and genotypes from subjects with virologic failure. The International AIDS Society-USA genotypic resistance guidelines were used to calculate regimen resistance cost (RCreg) and number of active drug (AD) scores for each regimen and to rank the regimens.

Results: Intra- and interstudy comparisons showed higher VS rates for nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens (range: 51%-76%) and boosted protease inhibitor (boosted PI) regimens (range: 55%-79%). Boosted PI failures had the lowest RCreg (range: 0.12-0.21) and the highest AD (range: 19.80-20.18) scores. NNRTI failures had higher RCreg (range: 0.00-1.22) and lower AD (range: 16.83-21) scores.

Conclusions: NNRTI and boosted PI regimens provide the highest rates of VS in treatment-naive HIV-infected persons. Treatment option scores were higher in subjects who failed boosted PI- containing regimens versus NNRTI-containing regimens, however.

Publication types

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

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • Drug Resistance, Viral* / genetics
  • Genotype
  • HIV / drug effects*
  • HIV / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Meta-Analysis as Topic
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

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