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Review
. 2012 Jan 14;26(2):185-92.
doi: 10.1097/QAD.0b013e32834e9d7d.

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

Jonathan Z Li  1 , Roger Paredes, Heather J Ribaudo, Evguenia S Svarovskaia, Michael J Kozal, Katherine H Hullsiek, Michael D Miller, David R Bangsberg, Daniel R Kuritzkes
Affiliations
Review

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

Jonathan Z Li et al. AIDS. .

Abstract

Objectives: To evaluate the risk of virologic failure conferred by suboptimal adherence to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and minority NNRTI resistance mutations.

Design: Pooled analysis of the risk of virologic failure conferred by minority NNRTI resistance mutations and NNRTI adherence from three studies of treatment-naïve individuals initiating an NNRTI-based regimen.

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.

Conclusions: The presence of minority NNRTI resistance mutations and NNRTI adherence were found to be independent predictors of virologic failure, but also modify each other's effects on virologic failure. In addition to the focus on medication adherence counseling, ultrasensitive HIV-1 drug resistance assays could play a role in optimizing the success rates of first-line antiretroviral therapy.

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Conflict of interest statement

Financial Disclosures and Conflicts of Interest: No other potential conflicts of interest relevant to this article were reported.

Figures

Fig. 1
Fig. 1. NNRTI adherence and virologic failure rates by adherence quartiles
(a) Box plot of NNRTI adherence by adherence quartiles. Participants from each study were stratified into quartiles by adherence and participants from each quartile then combined. (b) Rates of virologic failure by adherence quartiles. P values represent Fisher’s exact test comparing virologic failure rate for quartile 1 versus each of the other quartiles. (c) Virologic failure rates by adherence quartile stratified by presence of NNRTI minority variants. MV, minority variants.
Fig. 2
Fig. 2. Virologic failure rates by NNRTI adherence strata
(a) Rates of virologic failure by adherence categories. (b) Virologic failure rates by adherence categories stratified by presence of NNRTI minority variants. MV, minority variants.
Fig. 3
Fig. 3. Relationship between the presence of NNRTI minority variants and risk of virologic failure differs by levels of medication adherence
Hazard ratios are from the Cox proportional hazard model using NNRTI adherence over the most recent 60 days in a time-updated analysis.
See this image and copyright information in PMC

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