Secondary Mutations in the Protease Region of Human Immunodeficiency Virus and Virologic Failure in Drug-Naive Patients Treated with Protease Inhibitor-Based Therapy
The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor—containing antiretroviral regimen. Genotypic testing was performed on pl...
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| Veröffentlicht in: | The Journal of infectious diseases 2001-10, Vol.184 (8), p.983-991 |
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| container_title | The Journal of infectious diseases |
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| creator | Perno, Carlo F. Cozzi-Lepri, Alessandro Balotta, Claudia Forbici, Federica Violin, Michela Bertoli, Ada Facchi, Guido Pezzotti, Patrizio Cadeo, Gianpiero Tositti, Giulio Pasquinucci, Sandro Pauluzzi, Sergio Scalzini, Alfredo Salassa, Bernardino Vincenti, Antonella Phillips, Andrew N. Dianzani, Ferdinando Appice, Amelia Angarano, Gioacchino Monno, Laura Ippolito, Giuseppe Moroni, Mauro Monforte, Antonella d'Arminio |
| description | The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor—containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P=.04, χ2 test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30–3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy |
| doi_str_mv | 10.1086/323604 |
| format | Article |
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Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30–3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/323604</identifier><identifier>PMID: 11574912</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>Acute Disease ; Antibiotics. Antiinfectious agents. 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Study Group</creatorcontrib><creatorcontrib>Italian Cohort Naive Antiretroviral (I.CO.N.A.) Study Group</creatorcontrib><creatorcontrib>the Italian Cohort Naive Antiretroviral (I.CO.N.A.) Study Group</creatorcontrib><title>Secondary Mutations in the Protease Region of Human Immunodeficiency Virus and Virologic Failure in Drug-Naive Patients Treated with Protease Inhibitor-Based Therapy</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><addtitle>The Journal of Infectious Diseases</addtitle><description>The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor—containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P=.04, χ2 test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30–3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy</description><subject>Acute Disease</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Antiretrovirals</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antivirals</subject><subject>Biological and medical sciences</subject><subject>Chronic Disease</subject><subject>Codons</subject><subject>Cohort Studies</subject><subject>Databases as Topic</subject><subject>Genetic mutation</subject><subject>Genotype</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV 1</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - transmission</subject><subject>HIV Protease - genetics</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Major Article</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Odds Ratio</subject><subject>Pharmacology. Drug treatments</subject><subject>RNA</subject><subject>Treatment Failure</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. 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Aids</topic><topic>Virology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perno, Carlo F.</creatorcontrib><creatorcontrib>Cozzi-Lepri, Alessandro</creatorcontrib><creatorcontrib>Balotta, Claudia</creatorcontrib><creatorcontrib>Forbici, Federica</creatorcontrib><creatorcontrib>Violin, Michela</creatorcontrib><creatorcontrib>Bertoli, Ada</creatorcontrib><creatorcontrib>Facchi, Guido</creatorcontrib><creatorcontrib>Pezzotti, Patrizio</creatorcontrib><creatorcontrib>Cadeo, Gianpiero</creatorcontrib><creatorcontrib>Tositti, Giulio</creatorcontrib><creatorcontrib>Pasquinucci, Sandro</creatorcontrib><creatorcontrib>Pauluzzi, Sergio</creatorcontrib><creatorcontrib>Scalzini, Alfredo</creatorcontrib><creatorcontrib>Salassa, Bernardino</creatorcontrib><creatorcontrib>Vincenti, Antonella</creatorcontrib><creatorcontrib>Phillips, Andrew N.</creatorcontrib><creatorcontrib>Dianzani, Ferdinando</creatorcontrib><creatorcontrib>Appice, Amelia</creatorcontrib><creatorcontrib>Angarano, Gioacchino</creatorcontrib><creatorcontrib>Monno, Laura</creatorcontrib><creatorcontrib>Ippolito, Giuseppe</creatorcontrib><creatorcontrib>Moroni, Mauro</creatorcontrib><creatorcontrib>Monforte, Antonella d'Arminio</creatorcontrib><creatorcontrib>Italian Cohort Naive Antiretroviral (I.CO.N.A.) 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Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P=.04, χ2 test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30–3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>11574912</pmid><doi>10.1086/323604</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 2001-10, Vol.184 (8), p.983-991 |
| issn | 0022-1899 1537-6613 |
| language | eng |
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| source | Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Acute Disease Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral Therapy, Highly Active Antiretrovirals Antiviral agents Antiviral Agents - therapeutic use Antivirals Biological and medical sciences Chronic Disease Codons Cohort Studies Databases as Topic Genetic mutation Genotype Highly active antiretroviral therapy HIV HIV 1 HIV Infections - drug therapy HIV Infections - transmission HIV Protease - genetics Human immunodeficiency virus Human viral diseases Humans Infectious diseases Major Article Medical sciences Mutation Odds Ratio Pharmacology. Drug treatments RNA Treatment Failure Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Virology Viruses |
| title | Secondary Mutations in the Protease Region of Human Immunodeficiency Virus and Virologic Failure in Drug-Naive Patients Treated with Protease Inhibitor-Based Therapy |
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