Relationship between minority nonnucleoside reverse transcriptase inhibitor resistance mutations, adherence, and the risk of virologic failure.

Methods: Participants from each study were categorized into both adherence quartiles (Q1-Q4) and four strata: at least 95%, 80-94%, 60-79%, and below 60%. Weighted Cox proportional hazard models were used to estimate the risk of virologic failure.

Results: The majority of participants (N = 768) had high measured adherence, but those in the lowest adherence quartile had the highest proportion of participants with virologic failure and the risk of virologic failure increased step-wise with adherence below 95%. Detection of minority NNRTI drug resistance mutations increased the proportion of participants with virologic failure across adherence quartiles (Cochran-Mantel-Haenszel P  0.001) and adherence strata [Cochran-Mantel-Haenszel P  0.001; 60% adherence, hazard ratio 1.7 (1.1-2.7), P = 0.02; 60-79% adherence, hazard ratio 1.2 (0.5-3.2), P = 0.67; 80-94% adherence, hazard ratio 2.5 (0.98-6.3), P = 0.06; ≥95% adherence, hazard ratio 3.6 (2.3-5.6), P  0.001]. On multivariate analysis, the effect of minority variants was also most prominent at higher levels of medication adherence.

Conclusion: The majority of participants (N = 768) had high measured adherence, but those in the lowest adherence quartile had the highest proportion of participants with virologic failure and the risk of virologic failure increased step-wise with adherence below 95%. Detection of minority NNRTI drug resistance mutations increased the proportion of participants with virologic failure across adherence quartiles (Cochran-Mantel-Haenszel P  0.001) and adherence strata [Cochran-Mantel-Haenszel P  0.001; 60% adherence, hazard ratio 1.7 (1.1-2.7), P = 0.02; 60-79% adherence, hazard ratio 1.2 (0.5-3.2), P = 0.67; 80-94% adherence, hazard ratio 2.5 (0.98-6.3), P = 0.06; ≥95% adherence, hazard ratio 3.6 (2.3-5.6), P  0.001]. On multivariate analysis, the effect of minority variants was also most prominent at higher levels of medication adherence.