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

Metzner, K. J.; Bonhoeffer, Sebastian; Fischer, Marek; Karanicolas, Rose; Allers, Kristina; Joos, Beda; Weber, Rainer; Hirschel, Bernard; Kostrikis, L. G.; Gunthard, Huldrych

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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 Hirschel, Bernard Kostrikis, L. G. Gunthard, Huldrych show all authors [1 - 10]
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		Adult — Aged — Anti-HIV Agents/ administration & dosage/pharmacology — Antiretroviral Therapy, Highly Active/ methods — Cohort Studies — Drug Administration Schedule — Drug Resistance, Viral/genetics — Female — HIV Infections/blood/ drug therapy/ virology — HIV-1/ genetics — Humans — Male — Middle Aged — Point Mutation — RNA, Viral/blood/genetics — Reverse Transcriptase Polymerase Chain Reaction
Identifiers		DOI: 10.1086/379215 PMID: 14624368
Full text		Article - Limited access to UNIGE Other version: http://www.journals.uchicago.edu/doi/full/10.1086/379215
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Citation (ISO format)		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