Low-Frequency HIV-1 Drug Resistance Mutations and Risk of NNRTI-Based Antiretroviral Treatment Failure: A Systematic Review and Pooled Analysis

CONTEXT Presence of low-frequency, or minority, human immunodeficiency virus type 1 (HIV-1) drug resistance mutations may adversely affect response to antiretroviral treatment (ART), but evidence regarding the effects of such mutations on the effectiveness of first-line ART is conflicting. OBJECTIVE...

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Published in:JAMA : the journal of the American Medical Association 2011-04, Vol.305 (13), p.1327-1335
Main Authors: Li, Jonathan Z, Paredes, Roger, Ribaudo, Heather J, Svarovskaia, Evguenia S, Metzner, Karin J, Kozal, Michael J, Hullsiek, Kathy Huppler, Balduin, Melanie, Jakobsen, Martin R, Geretti, Anna Maria, Thiebaut, Rodolphe, Ostergaard, Lars, Masquelier, Bernard, Johnson, Jeffrey A, Miller, Michael D, Kuritzkes, Daniel R
Format: Article
Language:English
Subjects:
Anti-Retroviral Agents - pharmacology
Antiretroviral drugs
Biological and medical sciences
Case-Control Studies
Cohort Studies
Drug resistance
Drug Resistance, Viral - genetics
General aspects
HIV
HIV Infections - drug therapy
HIV-1 - genetics
Human immunodeficiency virus
Human immunodeficiency virus 1
Human viral diseases
Humans
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunopathology
Infectious diseases
Medical sciences
Mutation
Risk
Risk factors
Systematic review
Treatment Failure
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
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Summary:CONTEXT Presence of low-frequency, or minority, human immunodeficiency virus type 1 (HIV-1) drug resistance mutations may adversely affect response to antiretroviral treatment (ART), but evidence regarding the effects of such mutations on the effectiveness of first-line ART is conflicting. OBJECTIVE To evaluate the association of preexisting drug-resistant HIV-1 minority variants with risk of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)–based antiretroviral virologic failure. DATA SOURCES Systematic review of published and unpublished studies in PubMed (1966 through December 2010), EMBASE (1974 through December 2010), conference abstracts, and article references. Authors of all studies were contacted for detailed laboratory, ART, and adherence data. STUDY SELECTION AND DATA ABSTRACTION Studies involving ART-naive participants initiating NNRTI-based regimens were included. Participants were included if all drugs in their ART regimen were fully active by standard HIV drug resistance testing. Cox proportional hazard models using pooled patient-level data were used to estimate the risk of virologic failure based on a Prentice weighted case-cohort analysis stratified by study. DATA SYNTHESIS Individual data from 10 studies and 985 participants were available for the primary analysis. Low-frequency drug resistance mutations were detected in 187 participants, including 117 of 808 patients in the cohort studies. Low-frequency HIV-1 drug resistance mutations were associated with an increased risk of virologic failure (hazard ratio (HR], 2.3 [95% confidence interval {CI}, 1.7-3.3]; P 
ISSN:0098-7484
1538-3598
DOI:10.1001/jama.2011.375