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Title

Emergence of minor populations of human immunodeficiency virus type 1 carrying the M184V and L90M mutations in subjects undergoing structured treatment interruptions

Authors
Metzner, K. J.
Bonhoeffer, Sebastian
Fischer, Marek
Karanicolas, Rose
Allers, Kristina
Joos, Beda
Weber, Rainer
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Published in Journal of Infectious Diseases. 2003, vol. 188, no. 10, p. 1433-1443
Abstract The use of structured treatment interruption (STI) in human immunodeficiency virus (HIV)-infected subjects is currently being studied as an alternative therapeutic strategy for HIV-1. The potential risk for selection of drug-resistant HIV-1 variants during STI is unknown and remains a concern. Therefore, the emergence of drug resistance in sequential plasma samples obtained from 28 subjects with chronic HIV infection was studied. They underwent 4 cycles of 2-week STI, followed by 8-week retreatment with highly active antiretroviral therapy identical to that used before STI, and they had never failed treatment before undergoing STI. At week 40, treatment was stopped for a longer period. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction, by use of allele-discriminating oligonucleotides for 2 key resistance mutations: L90M (protease) and M184V (reverse transcriptase). The approximate discriminative power was 0.1%. In 14 of 25 and in 3 of 25 subjects, the M184V and the L90M mutations, respectively, were detected as minor populations, at different times during STI. Overall, these results indicate that, in subjects undergoing multiple STIs, HIV-1 variants carrying drug-resistance mutations can emerge during periods of increased HIV-1 replication.
Keywords AdultAgedAnti-HIV Agents/ administration & dosage/pharmacologyAntiretroviral Therapy, Highly Active/ methodsCohort StudiesDrug Administration ScheduleDrug Resistance, Viral/geneticsFemaleHIV Infections/blood/ drug therapy/ virologyHIV-1/ geneticsHumansMaleMiddle AgedPoint MutationRNA, Viral/blood/geneticsReverse Transcriptase Polymerase Chain Reaction
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PMID: 14624368
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Other version: http://www.journals.uchicago.edu/doi/full/10.1086/379215
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METZNER, K. J. et al. Emergence of minor populations of human immunodeficiency virus type 1 carrying the M184V and L90M mutations in subjects undergoing structured treatment interruptions. In: Journal of Infectious Diseases, 2003, vol. 188, n° 10, p. 1433-1443. https://archive-ouverte.unige.ch/unige:7431

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Deposited on : 2010-06-21

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