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Selection of Drug-Resistant HIV-1 During the Early Phase of Viral Decay Is Uncommon in Treatment-Naive Patients Initiated on a Three- or Four-Drug Antiretroviral Regimen Including Lamivudine

Bergroth, T; Ekici, H; Gisslen, M; Kinloch-de Loes, S; Goh, LE; Freedman, A; Lampe, F; ... Sonnerborg, A; + view all (2009) Selection of Drug-Resistant HIV-1 During the Early Phase of Viral Decay Is Uncommon in Treatment-Naive Patients Initiated on a Three- or Four-Drug Antiretroviral Regimen Including Lamivudine. J MED VIROL , 81 (1) 1 - 8. 10.1002/jmv.21363.

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Abstract

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-naive HIV-1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment-naive 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-naive adherent patients is potent enough to prevent development of resistance during the first months of therapy. J. Med. Virol. 81:1-8, 2009. (c) 2008 Wiley-Liss, Inc.

Type: Article
Title: Selection of Drug-Resistant HIV-1 During the Early Phase of Viral Decay Is Uncommon in Treatment-Naive Patients Initiated on a Three- or Four-Drug Antiretroviral Regimen Including Lamivudine
DOI: 10.1002/jmv.21363
Keywords: HIV-1, minor populations, anti-retroviral treatment, resistance, selective real-time PCR, M184I/V, IMMUNODEFICIENCY-VIRUS TYPE-1, STRUCTURED TREATMENT INTERRUPTIONS, CD4 CELL COUNTS, MINORITY POPULATIONS, COMBINATION THERAPY, PROTEASE INHIBITORS, CUBIC MILLIMETER, INFECTION, LYMPHOCYTES, MUTATIONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
URI: http://discovery.ucl.ac.uk/id/eprint/1305990
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