ArticleThe Journal of antimicrobial chemotherapy2014
Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy.Antimicrobial agents and chemotherapy · 2016Trial
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- HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.The Journal of antimicrobial chemotherapy · 2020Article
- Baseline PI susceptibility by HIV-1 Gag-protease phenotyping and subsequent virological suppression with PI-based second-line ART in Nigeria.The Journal of antimicrobial chemotherapy · 2019Article
- Evolution of gag and gp41 in Patients Receiving Ritonavir-Boosted Protease Inhibitors.Scientific reports · 2017Article
- Virological Outcomes of Second-line Protease Inhibitor-Based Treatment for Human Immunodeficiency Virus Type 1 in a High-Prevalence Rural South African Setting: A Competing-Risks Prospective Cohort Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017Article
- Human Immunodeficiency Virus-1 Sequence Changes and Drug Resistance Mutation Among Virologic Failures of Lopinavir/Ritonavir Monotherapy: AIDS Clinical Trials Group Protocol A5230.Open forum infectious diseases · 2016Article
- HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir.The Journal of antimicrobial chemotherapy · 2015Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
objectivesMajor protease mutations are rarely observed following first-line failure with PIs and interpretation of genotyping results in this context may be difficult. We performed extensive phenotyping of viruses from five patients failing lopinavir/ritonavir monotherapy in the MONARK study without major PI mutations by standard genotyping.
methodsPhenotypic susceptibility testing and viral infectivity assessments were performed using a single-cycle assay and fold changes (FC) relative to a lopinavir-susceptible reference strain were calculated.
results>10-fold reduced baseline susceptibility to lopinavir occurred in two of five patients and >5-fold in another two. Four of five patients exhibited phylogenetic evidence of a limited viral evolution between baseline and failure, with amino acid changes at drug resistance-associated positions in one: T81A emerged in Gag with M36I in the protease gene, correlating with a reduction in lopinavir susceptibility from FC 7 (95% CI 6-8.35) to FC 13 (95% CI 8.11-17.8). Reductions in darunavir susceptibility (>5 FC) occurred in three individuals. DISCUSSION: This study suggests both baseline reduced susceptibility and evolution of resistance could be contributing factors to PI failure, despite the absence of classical PI resistance mutations by standard testing methods. Use of phenotyping also reveals lower darunavir susceptibility, warranting further study as this agent is commonly used following lopinavir failure.
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