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, 80(3):325–329, nov, 2019. ![A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy [link]](https://bibbase.org/img/filetypes/link.svg "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},
number = {3},
pages = {325--329},
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},
volume = {80},
year = {2019}
}
Downloads: 0
{"_id":"YewWivyQ8Kx6Pqdqn","bibbaseid":"cohen-stewart-kengne-leisegang-coetsee-maharaj-dunn-hislop-etal-aclinicalpredictionruleforproteaseinhibitorresistanceinpatientsfailingsecondlineantiretroviraltherapy-2019","author_short":["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."],"bibdata":{"bibtype":"article","type":"article","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":[{"propositions":[],"lastnames":["Cohen"],"firstnames":["Karen"],"suffixes":[]},{"propositions":[],"lastnames":["Stewart"],"firstnames":["Annemie"],"suffixes":[]},{"propositions":[],"lastnames":["Kengne"],"firstnames":["Andre","P"],"suffixes":[]},{"propositions":[],"lastnames":["Leisegang"],"firstnames":["Rory"],"suffixes":[]},{"propositions":[],"lastnames":["Coetsee"],"firstnames":["Marla"],"suffixes":[]},{"propositions":[],"lastnames":["Maharaj"],"firstnames":["Shavani"],"suffixes":[]},{"propositions":[],"lastnames":["Dunn"],"firstnames":["Liezl"],"suffixes":[]},{"propositions":[],"lastnames":["Hislop"],"firstnames":["Michael"],"suffixes":[]},{"propositions":["van"],"lastnames":["Zyl"],"firstnames":["Gert"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme","A"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]}],"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","number":"3","pages":"325–329","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","volume":"80","year":"2019","bibtex":"@article{Cohen2018,\r\nabstract = {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.},\r\nauthor = {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},\r\ndoi = {10.1097/QAI.0000000000001923},\r\njournal = {JAIDS Journal of Acquired Immune Deficiency Syndromes},\r\nkeywords = {fund{\\_}not{\\_}ack,original},\r\nmendeley-tags = {fund{\\_}not{\\_}ack,original},\r\nmonth = {nov},\r\nnumber = {3},\r\npages = {325--329},\r\npmid = {30531296},\r\ntitle = {{A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy}},\r\nurl = {http://insights.ovid.com/crossref?an=00126334-900000000-96498},\r\nvolume = {80},\r\nyear = {2019}\r\n}\r\n","author_short":["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."],"key":"Cohen2018","id":"Cohen2018","bibbaseid":"cohen-stewart-kengne-leisegang-coetsee-maharaj-dunn-hislop-etal-aclinicalpredictionruleforproteaseinhibitorresistanceinpatientsfailingsecondlineantiretroviraltherapy-2019","role":"author","urls":{"Paper":"http://insights.ovid.com/crossref?an=00126334-900000000-96498"},"keyword":["fund_not_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["fund_not_ack","original"],"search_terms":["clinical","prediction","rule","protease","inhibitor","resistance","patients","failing","second","line","antiretroviral","therapy","cohen","stewart","kengne","leisegang","coetsee","maharaj","dunn","hislop","van zyl","meintjes","maartens"],"title":"A clinical prediction rule for protease inhibitor resistance in patients failing second-line antiretroviral therapy","year":2019}