Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens

Autor: Manuel Castaño, Juan Pasquau-Liaño, Manuel Márquez-Solero, Luis F. López-Cortés, Dolores Merino, Jose M. Fajardo-Pico, David Vinuesa-García, Miguel Ángel López-Ruz, Francisco Tellez-Pérez, Patricia Jiménez-Aguilar, Guillermo Ojeda-Burgos, Alberto Romero-Palacios, Zaira R. Palacios-Baena, Pompeyo Viciana, Alberto Terrón-Pernía, María J. Ríos-Villegas, José Hernández-Quero, Francisco Orihuela-Cañadas
Přispěvatelé: [López-Cortés,LF, Viciana,P] Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. [Castaño,MA, Orihuela-Cañadas,F] Hospital Universitario Carlos Haya, Málaga, Spain. [López-Ruz,MA, Pasquau-Liaño,J] Hospital Universitario Virgen de las Nieves, Granada, Spain. [Rios-Villegas,MJ, Palacios-Baena,Z] Hospital Universitario Virgen Macarena, Sevilla, Spain. [Hernández-Quero,J, Vinuesa-Garcia,D] Hospital Universitario San Cecilio, Granada, Spain. [Merino,D, Fajardo-Pico,JM] Complejo Hospitalario Juan Ramón Jiménez, Huelva, Spain. [Jiménez-Aguilar,P, Romero-Palacios,A] Hospital Universitario de Puerto Real, Cádiz, Spain. [Marquez-Solero,M, Ojeda-Burgos] Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Terrón-Pernía,A] Hospital Jerez de la Frontera, Cádiz, Spain. [Tellez-Pérez,F] Hospital La Línea, Cádiz, Spain., Sociedad Andaluza de Enfermedades Infecciosas
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Oncology
Male
medicine.medical_treatment
DNA Mutational Analysis
HIV Infections
Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Aspartic Acid Proteases::Aspartic Acid Endopeptidases::HIV Protease [Medical Subject Headings]
Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes
Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [Medical Subject Headings]

Pathology and Laboratory Medicine
Biochemistry
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
0302 clinical medicine
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Retrospective Studies [Medical Subject Headings]

Immunodeficiency Viruses
Clinical endpoint
Análisis de intención de tratar
Public and Occupational Health
Inhibidores de proteasas
Enzyme Inhibitors
lcsh:Science
Aged
80 and over

Antiretrovirals
Health Care::Health Care Quality
Access
and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic::Intention to Treat Analysis [Medical Subject Headings]

Medical Microbiology
Viral Pathogens
Viral load
medicine.medical_specialty
Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings]
030106 microbiology
Immunology
Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds
1-Ring::Pyrimidines::Pyrimidinones::Lopinavir [Medical Subject Headings]

Microbiology
03 medical and health sciences
Humans
Protease inhibitor (pharmacology)
Protease Inhibitors
Microbial Pathogens
Aged
Retrospective Studies
Pharmacology
Protease
lcsh:R
Linfocitos T CD4-Positivos
Organisms
Diseases::Virus Diseases::Viremia [Medical Subject Headings]
Biology and Life Sciences
Proteins
Infecciones por VIH
Regimen
Mutation
HIV-1
lcsh:Q
Preventive Medicine
0301 basic medicine
RNA viruses
Viral Diseases
lcsh:Medicine
Kaplan-Meier Estimate
Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings]
Lopinavir
HIV Protease
Medicine and Health Sciences
030212 general & internal medicine
Darunavir
Multidisciplinary
Protease Inhibitor Therapy
Antimicrobials
Drugs
Diseases::Bacterial Infections and Mycoses::Infection::Coinfection [Medical Subject Headings]
Proteases
Viral Load
Middle Aged
Antivirals
Vaccination and Immunization
Enzymes
Infectious Diseases
Treatment Outcome
Viruses
Female
Pathogens
medicine.drug
Research Article
Adult
Adolescent
Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Thiazoles::Ritonavir [Medical Subject Headings]
Antiretroviral Therapy
Young Adult
Antiviral Therapy
Internal medicine
Microbial Control
Virology
Retroviruses
Drug Resistance
Viral

medicine
Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings]
Viremia
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings]

Ritonavir
Mutación
business.industry
Lentivirus
HIV
HIV Protease Inhibitors
Enzymology
Coinfección
business
Viral Transmission and Infection
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 2, p e0148924 (2016)
Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1932-6203
Popis: López-Cortés, Luis F. et al.
[Background and Objective] Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI)-based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens. [Methods] This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). [Results] A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI, 76.8-81.8) and 91.5% (CI, 89.6-93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. [Conclusion] Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug.
All of the authors are members of the Sociedad Andaluza de Enfermedades Infecciosas (Andalusian Society of Infectious Diseases. http://www.saei.org/), which is the sponsor of this study.
Databáze: OpenAIRE