ABSTRACT
BACKGROUND: Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy. METHODS: The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries. Genotypic resistance was interpreted using the ANRS algorithm. Phenotypic resistance was predicted using the Virco geno- to phenotype system. RESULTS: 80.7% of the sequences included at least one drug-resistance mutation. Mutations were found for NRTIs (73.5%), NNRTIs (48.5%), and protease inhibitors (35.8%). Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. Among NRTIs, resistance was most frequently predicted for lamivudine. About half of all sequences had reduced susceptibility for NNRTIs. Resistance to most boosted protease inhibitors was found in < 25%. No sequence had resistance to all currently available drugs. CONCLUSION: Levels of resistance among patients with therapy failure were high. The patterns of resistance reflect resistance to drugs available for a longer time. Fully suppressive regimens can be designed even for the most mutated HIV because boosted protease inhibitors have remained active against most circulating viruses and new drug classes have become available.
Subject(s)
Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV-1/genetics , Adult , Amino Acid Substitution , Europe , Female , Genotype , HIV Infections/virology , HIV Protease/genetics , HIV Protease Inhibitors/therapeutic use , HIV Reverse Transcriptase/genetics , Humans , Male , Middle Aged , Mutation , Sequence Analysis, Protein , Treatment FailureABSTRACT
BACKGROUND: The purpose of this study was to recognize nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV-1 strains among a group of therapy-naive patients, and subsequently to guide the choice of antiretroviral therapy. PATIENTS AND METHODS: HIV strains present in sera of 128 antiretroviral therapy-naive patients were tested for NRTI resistance-associated mutations. The RT-PCR amplified HIV rt regions were analyzed with an INNI-LiPA-HIV-1 RT assay. The number and pattern of resistance-associated mutated codons were determined and interpreted as resistance to particular drugs. RESULTS: Mutated codons were detected in 66 (51.5%) out of 128 tested samples. In 54 (81.8%) out of 66 samples, a K70R mutation was identified, which was followed by an M184V mutation in 22 cases (33.3%). For a majority of these samples, mixed wild/mutant populations were recognized in 44 (66.6%) cases. The interpretation of hybridization data revealed drug-resistant strains in 37 (28.9%) out of all samples tested. The determined resistance to particular drugs was as follows: 20 strains were resistant to zidovudine (ZDV), ten to lamivudine (3TC) and six to didanosine (ddI)/zalcitabine (ddC)/abacavir (ABC). In one case, a ZDV/3TC-resistant HIV strain was found. CONCLUSION: The prevalence of mutations associated with NRTI resistance was high in the tested cohort. The key reasons for that were most probably needle and drug sharing within the group of intravenous drug users (IVDUs) and the use of ZDV in monotherapeutic regimes in the early 1990s.
