Comparative analysis of HIV type 1 genotypic resistance across antiretroviral trial treatment regimens

P. B. Gilbert*, G. J. Hanna, V. De Gruttola, J. Martinez-Picado, D. R. Kuritzkes, V. A. Johnson, D. D. Richman, R. T. D'Aquila

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

From data on HIV-1 genotypes collected from antiretroviral trial participants who fail virologically, we describe methods for comparing distributions of acquired HIV-1 mutations across different treatment regimens. Given a definition of a 'mutational distance' that summarizes the genetic change of a subject's virus in a way that captures the resistance cost of exposure to an antiretroviral regimen, these comparative analyses inform about the relative treatability of emergent virus by next-line therapy directed to the same viral target. The utility of the methods is illustrated by application to data from AIDS Clinical Trials Group (ACTG) Study 241. We find that patients failing zidovudine/didanosine/nevirapine accumulated a 2.41-fold greater nonnucleoside reverse transcriptase inhibitor (RTI) mutational distance than patients failing zidovudine/didanosine [95% confidence interval (1.55, 5.26), p < 0.000001], quantitating expectations that adding a nonnucleoside RTI to a double nucleoside regimen may attenuate future effectiveness of nonnucleoside RTI therapy for nucleoside-experienced patients if viremia is not suppressed. We also find that persons with extensive prior experience with suboptimal nucleoside therapy who were virologically failing zidovudine/didanosine/nevirapine or zidovudine/didanosine accumulated a similar nucleoside RTI mutational distance, implying that the addition of the nonnucleoside RTI did not preserve future nucleoside options.

Original languageEnglish (US)
Pages (from-to)1325-1336
Number of pages12
JournalAIDS research and human retroviruses
Volume16
Issue number14
DOIs
StatePublished - Sep 20 2000

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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