Drug resistance increased risk for virologic failure with first-line ART
Li JZ. JAMA. 2011;305:1327-1335.
Researchers have identified an association between low-frequency HIV-1 drug resistance and an increased risk for first-line antiretroviral treatment failure, particularly mutations with non-nucleoside reverse transcriptase inhibitor resistance.
Patients with low frequency variants had a 2.5- to threefold increased risk for virologic failure. The higher the number of drug-resistant variants, the more likely a dose-dependent increased risk for virologic failure would occur, according to the researchers.
“The test that we currently use to identify these drug-resistant mutations is not perfect,” Jonathan Z. Li, MD,in the section of retroviral therapeutics at Brigham and Women’s Hospital, told Infectious Disease News. “We found that a more sensitive assay will identify additional mutations, the presence of which were associated with an increased risk for treatment failure and was most evident with mutations against NNRTIs, a key component of the most popular treatment regimen.”
Data on the effects of drug-resistant mutations among ART-naive participants initiating NNRTI-based regimens were pooled from published and unpublished studies included in PubMed, Embase and conference abstracts. The final cohort included 10 studies with 985 adults.
Those with either K103N or Y181C mutations were considered having an NNRTI-resistant low-frequency variant, and those with either M184V or K65R mutations were considered having an NRTI-resistant low-frequency variant, according to the report.
After controlling for medication adherence, race and ethnicity, baseline CD4 cell count, and plasma HIV-1 RNA levels, the researchers observed an increased risk for virologic failure among 187 participants with low-frequency drug-resistant mutations (HR=2.3; 95% CI, 1.7-3.3).
Although the presence of any NNRTI- or NRTI-resistant low-frequency variant was associated with an increased risk for virologic failure, the strongest association was observed with low frequency variants resistant to NNRTIs (HR=2.6; 95% CI, 1.9-3.5). Further, when compared with 15% of participants without minority variants, 35% of participants with detectable low-frequency variants experienced virologic failure.
“These data provide a rationale for developing standardized clinical assays for the detection of NNRTI-resistant minority variants,” the researchers wrote. “Because NNRTI-based regimens are the most commonly prescribed first-line antiretroviral therapy, the clinical use of ultrasensitive screening for drug-resistant HIV could help identify individuals at greatest risk for virologic failure and allow ART to be tailored appropriately.” – by Ashley DeNyse
Disclosure: Dr. Li has received research support from Bristol-Myers Squibb and has served as a consultant to Tibotec.
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