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Absence of zidovudine resistance in antiretroviral-naive patients following zidovudine/lamivudine/protease inhibitor combination therapy: virological evaluation of the AVANTI 2 and AVANTI 3 studies

Absence of zidovudine resistance in antiretroviral-naive patients following zidovudine/lamivudine/protease inhibitor combination therapy: virological evaluation of the AVANTI 2 and AVANTI 3 studies

Aids 14(9): 1195-1201

Objectives: To assess the role of resistance mutations in subjects experiencing virological failure on zidovudine (ZDV) and lamivudine (3TC) combined with a protease inhibitor (PI) to those failing on ZDV/3TC alone. Design and methods: Samples were obtained from previously antiretroviral therapy-naive subjects enrolled into two studies, AVANTI 2 and AVANTI 3. Subjects were randomized to receive either: ZDV/3TC or ZDV/3TC plus indinavir (IDV) for 52 weeks (AVANTI 2), and ZDV/3TC or ZDV/3TC and nelfinavir (NFV) for 28 weeks (AVANTI 3). Emergence of viral resistance mutations was monitored by population sequencing and phenotypic resistance was determined by the recombinant virus assay. Results: Genotypic data were obtained for subjects with plasma HIV-1 RNA > 400 copies/ml. In AVANTI 2, ZDV mutations were detected in 27% of ZDV/3TC-treated patients at week 52, but were absent in subjects treated with ZDV/3TC/IDV. No subjects from either arm of AVANTI 3 developed ZDV resistance mutations at week 28. The M184V mutation developed in most ZDV/3TC-treated subjects from both studies. The presence of M184V was, however, associated with significantly lower plasma viral RNA levels when compared with values obtained before initiation of treatment. There was a high frequency (4 of 11) of the protease L10F substitution in ZDV/3TC/IDV-treated patients that was associated virological failure but did not result in phenotypic resistance to any of the PIs tested. Conclusions: ZDV mutations were not detected in ZDV/3TC/PI-treated patients and they developed slowly in those treated with ZDV/3TC. Few protease mutations known to confer phenotypic PI resistance developed in the ZDV/3TC/PI arms of either study. The low prevalence of ZDV and PI mutations is encouraging regarding the future treatment options of these patients.

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Accession: 010112864

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PMID: 10894284

DOI: 10.1097/00002030-200006160-00017

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