A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy.

BACKGROUND: Most adults with virological failure on second-line ART in resource limited settings have no major protease inhibitor (PI) resistance mutations. Therefore, empiric switches to third-line ART would waste resources. Genotypic antiretroviral resistance testing (GART) is expensive and has limited availability. A clinical prediction rule (CPR) for PI resistance could rationalise access to GART.

SETTING: A private sector ART cohort, South Africa.

METHODS: We identified adults with virologic failure on ritonavir-boosted lopinavir/atazanavir-based ART and GART. We constructed a multivariate logistic regression model including age, sex, PI duration, short-term adherence (using pharmacy claims), concomitant CYP3A4-inducing drugs, and viral load at time of GART. We selected variables for the CPR using a stepwise approach and internally validated the model by bootstrapping.

RESULTS: 148/339 (44%) patients had PI resistance (defined as ≥ 1 major resistance mutation to current PI). Median age was 42 years (interquartile range (IQR) 36-48), 212 (63%) were female, 308 (91%) were on lopinavir/ritonavir, median PI duration was 2.6 years (IQR 1.6-4.7). Variables associated with PI resistance and included in the CPR were age [adjusted odds ratio (aOR) 1.96 (95%CI 1.42-2.70) for 10-year increase]; PI duration [aOR 1.14 (95%CI 1.03-1.26) per year], adherence [aOR 1.22 (95%CI 1.12-1.33) per 10% increase]. The CPR model had a c-statistic of 0.738 (95% CI 0.686 to 0.791).

CONCLUSION: Older patients with high adherence and prolonged PI exposure are most likely to benefit from GART to guide selection of a third-line ART regimen. Our CPR to select patients for GART requires external validation before implementation.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.