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

TitleRelationship between minority nonnucleoside reverse transcriptase inhibitor resistance mutations, adherence, and the risk of virologic failure.
Publication TypeJournal Article
Year of Publication2012
AuthorsLi JZ, Paredes R, Ribaudo HJ, Svarovskaia ES, Kozal MJ, Hullsiek KH, Miller MD, Bangsberg DR, Kuritzkes DR
JournalAIDS
Volume26
Issue2
Pagination185-92
Date Published2012 Jan 14
ISSN1473-5571
KeywordsAdult, Anti-HIV Agents, CD4 Lymphocyte Count, Cohort Studies, Counseling, Drug Resistance, Viral, Female, HIV Infections, HIV-1, Humans, Male, Medication Adherence, Mutation, Reverse Transcriptase Inhibitors, Treatment Outcome, Viral Load
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.

DOI10.1097/QAD.0b013e32834e9d7d
Alternate JournalAIDS
PubMed ID22179227
PubMed Central IDPMC3437231
Grant ListK24 RR016482 / RR / NCRR NIH HHS / United States
K24 RR016482 / RR / NCRR NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
R01 MH054907 / MH / NIMH NIH HHS / United States
U01 AI 068636 / AI / NIAID NIH HHS / United States
U01 AI042170 / AI / NIAID NIH HHS / United States
U01 AI042170 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States