TY - JOUR
T1 - HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing
T2 - A substudy of AIDS Clinical Trials Group Protocol 388
AU - Demeter, Lisa M.
AU - Ribaudo, Heather J.
AU - Erice, Alejo
AU - Eshleman, Susan H.
AU - Hammer, Scott M.
AU - Hellmann, Nicholas S.
AU - Fischl, Margaret A.
N1 - Funding Information:
Financial support. National Institute of Health (NIH; grants AI-38851, AI-27658, AI-27661, AI-27675, and RR-00044) and Adult AIDS Clinical Trials Group (grants 96-VC010, 200VC003, 200VD003, and 200VC007). S.H.E. received support from the Pediatric AIDS Clinical Trials Group (grant 97-PVCL07), NIH (grant R29-34348), the HIV-1 Prevention Trials Network, the National Institute of Child Health & Human Development and the National Institute on Drug Abuse/National Institute of Mental Health (grants U01-AI-46745 and U01-AI-48054), and the Elizabeth Glaser Pediatric AIDS Foundation.
PY - 2004/8/15
Y1 - 2004/8/15
N2 - 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.
AB - 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.
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U2 - 10.1086/422518
DO - 10.1086/422518
M3 - Article
C2 - 15356820
AN - SCOPUS:4344637591
SN - 1058-4838
VL - 39
SP - 552
EP - 558
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -