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Selection of drug‐resistant HIV‐1 during the early phase of viral decay is uncommon in treatment‐naïve patients initiated on a three‐ or four‐drug antiretroviral regimen including lamivudine
Author(s) -
Bergroth Tobias,
Ekici Halime,
Gisslén Magnus,
Loes Sabine Kinlochde,
Goh LiEan,
Freedman Andrew,
Lampe Fiona,
Johnson Margaret A.,
Sönnerborg Anders
Publication year - 2009
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21363
Subject(s) - lamivudine , drug resistance , regimen , resistance mutation , medicine , virology , reverse transcriptase , zidovudine , viral load , virus , viral disease , biology , polymerase chain reaction , microbiology and biotechnology , genetics , hepatitis b virus , gene
Therapy failure due to drug resistance development is a common phenomenon in HIV‐infected patients. However, when the drug pressure leads to the earliest selection of drug‐resistant HIV‐1 populations is still unclear. In this study, the extent to which selection of the HIV‐1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment‐naïve HIV‐1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment‐naïve patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine‐containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real‐time PCR method. Among quadruple ART patients, who all were treated at primary HIV‐1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild‐type virus at baseline. No mutations were found in chronically infected patients on triple ART. In patients on dual therapy, M184I/V mutants were found frequently. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or four‐drug combination, in contrast to those receiving a less potent regimen. The results suggest that triple and quadruple lamivudine + PI or PI/r containing ART given to treatment‐naïve adherent patients is potent enough to prevent development of resistance during the first months of therapy. J. Med. Virol. 81:1–8, 2009. © 2008 Wiley‐Liss, Inc.