Hazelwood JD, Koel JL, Nail CD, Marangos M, Smith R, Miles S, Thompson M, Johnson VA; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 5th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 5th 1998 Chic Ill. 1998 Feb 1-5; 5th: 158 (abstract no. 421).
University of Alabama, Birmingham, AL.
Objective: To investigate potential mechanism(s) of therapeutic failure in primary care clinics, the genotypic patterns of drug resistance were investigated in HIV-1 isolates derived from selected pts (n=54) with rising plasma viral burden during double or triple combination antiretroviral therapy. Methods: Genotypic drug resistance profiles were linked to the pt's previous drug history, CD4+ cell profiles, and recent viral load results. HIV-infected PBMC from these pts at the time of virologic failure were cocultivated. Proviral DNA of cultured infected PBMC (n=42) or plasma HIV RNA by RT-PCR (n=3) were sequenced to determine the predominant genotype present within RT codons 1-242 and the entire protease gene using Affymetrix GeneChip nucleic acid sequencing technology. Phenotypic drug susceptibility testing was performed in parallel for 6 HIV-1 isolates. Results: Viruses were recovered from 42 of 54 subjects. 2- and 3-drug regimens at sampling included 1-3 NRTIs, 1 NNRTI and/or 1-2 PIs. ZDV- selected mutations persisted off ZDV greater than or equal to 1-2 years, whereas the 3TC-selected RT codon Ml84V was not predominant greater than or equal to 3-4 months off 3TC. d4T/ddI/ddC-selected RT mutations were rarely seen. Many patients received multiple sequential PIs with evidence of PI-selected mutations. Triple drug-selected mutations were identified in some, but not all, bulk viruses in infected PBMC (especially during ZDV/3TC/PI therapy). Although virologic failure was associated with detection of multiple RT/PI mutations during combination therapy in the majority of HIV-infected subjects, virologic failure was not uniformly linked to detectable genotypic resistance to each component agent in the current 2- or 3-drug regimen.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- Didanosine
- HIV
- HIV Infections
- HIV Protease
- HIV Protease Inhibitors
- HIV Seropositivity
- HIV-1
- Humans
- Lamivudine
- Stavudine
- Viral Load
- Zalcitabine
- Zidovudine
- reverse transcriptase, Human immunodeficiency virus 1
Other ID:
UI: 102236005
From Meeting Abstracts