Impact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure

Abstract

Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants increase the risk of virologic failure for first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We performed a pooled analysis to evaluate the relationship between NNRTI-resistant minority variants and the likelihood and types of resistance mutations detected at virologic failure. In multivariable logistic regression analysis, higher NNRTI minority variant copy numbers, non-white race, and nevirapine use were associated with a higher risk of NNRTI resistance at virologic failure. Among participants on efavirenz, K103N was the most frequently observed resistance mutation at virologic failure regardless of the baseline minority variant. However, the presence of baseline Y181C minority variant was associated with a higher probability of Y181C detection after virologic failure. NNRTI regimen choice and preexisting NNRTI-resistant minority variants were both associated with the probability and type of resistance mutations detected after virologic failure.

Figure 1.

Rates of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance detected at virologic failure increases with higher measured copy nos. of NNRTI-resistant minority variants (A) or measured and imputed copy nos. of NNRTI-resistant minority variants (B). For those without detectable minority variants (MVs) at baseline, MV copy nos. were imputed by using 10% of the assay limit of detection. Abbreviation: VF, virologic failure.

Figure 2.

Association between baseline minority nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation and the resistance detected by standard genotyping after virologic failure (VF) for those on an efavirenz-based regimen (A) or nevirapine-based regimen (B).