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HIV Drug Resistance Mutations Increase Virologic Failure

Last Updated: April 06, 2011.

Low-frequency HIV-1 drug resistance mutations are associated with increased risk of virologic failure with first-line antiretroviral treatment, according to a review published in the April 6 issue of the Journal of the American Medical Association.

WEDNESDAY, April 6 (HealthDay News) -- Low-frequency HIV-1 drug resistance mutations are associated with increased risk of virologic failure with first-line antiretroviral treatment (ART), according to a review published in the April 6 issue of the Journal of the American Medical Association.

Jonathan Z. Li, M.D., from Harvard Medical School in Boston, and colleagues examined the relationship between pre-existing drug-resistant HIV-1 minority variants and the risk of virologic failure of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral agents. A total of 10 cohort or case-control studies involving 985 ART-naive participants (808 in cohort studies) initiating NNRTI-based regimens were included. Drug-resistant HIV-1 minority variants were identified in 187 participants, including 117 from cohort studies.

The researchers identified an increased risk of virologic failure associated with low-frequency HIV-1 drug resistance mutations (hazard ratio [HR], 2.3) after controlling for confounders, including medication adherence, baseline CD4 count, and plasma HIV-1 RNA levels. Increased risk of virologic failure was significantly correlated with NNRTI resistance minority variants (HR, 2.6). Among cohort study participants, virologic failure was detected in 35 percent with detectable minority variants and 15 percent without minority variants. For medication adherence levels of 95 percent or greater, or less than 95 percent, the presence of minority variants was correlated with an increased risk of virologic failure (HR, 3.1 and 2.7, respectively). In participants with a higher proportion or quantity of drug-resistant variants, a dose-dependent increased risk of virologic failure was observed.

"Low-frequency HIV-1 drug resistance mutations, particularly involving NNRTI resistance, were significantly associated with a dose-dependent increased risk of virologic failure with first-line ART," the authors write.

Several of the study authors disclosed financial ties to the pharmaceutical industry.

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