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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Adult

Amino Acid Substitution

Anti-HIV Agents/*therapeutic use

Antiretroviral Therapy

Highly Active/*methods

Cohort Studies

*Drug Resistance

Viral

Female

HIV Infections/*drug therapy/*virology

HIV Reverse Transcriptase/genetics

HIV-1/*drug effects/isolation & purification

Humans

Lamivudine/*therapeutic use

Longitudinal Studies

Male

Middle Aged

Mutation

Missense

Plasma/virology

Polymerase Chain Reaction/methods

*Selection (Genetics)

Sequence Analysis

DNA

Viral Load

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)