A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy. Cohen, K., Stewart, A., Kengne, A. P, Leisegang, R., Coetsee, M., Maharaj, S., Dunn, L., Hislop, M., van Zyl, G., Meintjes, G. A, & Maartens, G. JAIDS Journal of Acquired Immune Deficiency Syndromes, nov, 2018.
A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy [link]Paper  doi  abstract   bibtex   
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.
@article{Cohen2018,
abstract = {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.},
author = {Cohen, Karen and Stewart, Annemie and Kengne, Andre P and Leisegang, Rory and Coetsee, Marla and Maharaj, Shavani and Dunn, Liezl and Hislop, Michael and van Zyl, Gert and Meintjes, Graeme A and Maartens, Gary},
doi = {10.1097/QAI.0000000000001923},
journal = {JAIDS Journal of Acquired Immune Deficiency Syndromes},
keywords = {fund{\_}not{\_}ack,original},
mendeley-tags = {fund{\_}not{\_}ack,original},
month = {nov},
pages = {1},
pmid = {30531296},
title = {{A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy}},
url = {http://insights.ovid.com/crossref?an=00126334-900000000-96498},
year = {2018}
}

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