López-Cortés, Luis FCastaño, Manuel ALópez-Ruz, Miguel ARios-Villegas, María JHernández-Quero, JoséMerino, DoloresJiménez-Aguilar, PatriciaMarquez-Solero, ManuelTerrón-Pernía, AlbertoTellez-Pérez, FranciscoViciana, PompeyoOrihuela-Cañadas, FranciscoPalacios-Baena, ZairaVinuesa-Garcia, DavidFajardo-Pico, Jose MRomero-Palacios, AlbertoOjeda-Burgos, GuillermoPasquau-Liaño, Juan2016-07-132016-07-132016-02-12López-Cortés LF, Castaño MA, López-Ruz MA, Rios-Villegas MJ, Hernández-Quero J, Merino D, et al. Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens. PLoS ONE. 2016; 11(2):e0148924http://hdl.handle.net/10668/2259Journal Article;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% (CI95, 76.8-81.8) and 91.5% (CI95, 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.enLinfocitos T CD4-PositivosCoinfecciónDarunavirInfecciones por VIHAnálisis de intención de tratarLopinavirMutaciónInhibidores de proteasasRitonavirMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-LymphocytesMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Infection::CoinfectionMedical Subject Headings::Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV InfectionsMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Aspartic Acid Proteases::Aspartic Acid Endopeptidases::HIV ProteaseMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::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 AnalysisMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::LopinavirMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease InhibitorsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Retrospective StudiesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Thiazoles::RitonavirMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment OutcomeMedical Subject Headings::Diseases::Virus Diseases::Viremiaresearch article26872331open access10.1371/journal.pone.01489241932-6203PMC4752289