HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing: A substudy of AIDS Clinical Trials Group Protocol 388

Lisa M. Demeter, Heather J. Ribaudo, Alejo Erice, Susan H. Eshleman, Scott M. Hammer, Nicholas S. Hellmann, Margaret A Fischl

Research output: Contribution to journalArticle

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Abstract

We evaluated phenotypic and genotypic markers of drug resistance in human immunodeficiency virus type 1 (HIV-1) at the time of virologic failure (VF) in subjects in the AIDS Clinical Trials Group Protocol 388 (ACTG 388) who received lamivudine-zidovudine (or lamivudine-stavudine) and either indinavir, efavirenz-indinavir, or nelfinavir-indinavir. At VF, phenotypically susceptible HIV-1 was found in 55% of subjects in the nelfinavir-indinavir arm, compared with 22% in the indinavir arm (P = .006). Phenotypic resistance to lamivudine was less common in the efavirenz-indinavir arm (33% of subjects; P = .002) and the nelfinavir-indinavir arm (43%; P = .003), compared with the indinavir arm (78%). Isolated phenotypic resistance to efavirenz at VF occurred in HIV-1 recovered from 33% of subjects in the efavirenz-indinavir arm; 24% of the subjects had HIV-1 with both efavirenz and lamivudine resistance. Results of genotypic tests were similar. The lower frequency of resistance in the nelfinavir-indinavir arm likely reflects decreased drug exposure that is due to intolerance, which is consistent with the lower potency and tolerability of this combination in ACTG 388. The lower frequency of lamivudine resistance in the efavirenz-indinavir arm is consistent with reports in other studies of potent regimens. Thus, although dual resistance to efavirenz and lamivudine occurred at VF in the efavirenz-indinavir arm, this risk was relatively low when evaluated in the context of the potency and tolerability of this regimen.

Original languageEnglish
Pages (from-to)552-558
Number of pages7
JournalClinical Infectious Diseases
Volume39
Issue number4
DOIs
StatePublished - Aug 15 2004

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efavirenz
Indinavir
Virus Diseases
Clinical Protocols
Drug Resistance
HIV-1
Acquired Immunodeficiency Syndrome
Clinical Trials
Lamivudine
Nelfinavir
Therapeutics
Stavudine
Zidovudine

ASJC Scopus subject areas

  • Immunology

Cite this

HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing : A substudy of AIDS Clinical Trials Group Protocol 388. / Demeter, Lisa M.; Ribaudo, Heather J.; Erice, Alejo; Eshleman, Susan H.; Hammer, Scott M.; Hellmann, Nicholas S.; Fischl, Margaret A.

In: Clinical Infectious Diseases, Vol. 39, No. 4, 15.08.2004, p. 552-558.

Research output: Contribution to journalArticle

Demeter, Lisa M. ; Ribaudo, Heather J. ; Erice, Alejo ; Eshleman, Susan H. ; Hammer, Scott M. ; Hellmann, Nicholas S. ; Fischl, Margaret A. / HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing : A substudy of AIDS Clinical Trials Group Protocol 388. In: Clinical Infectious Diseases. 2004 ; Vol. 39, No. 4. pp. 552-558.
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