Garcia, FedericoPoveda, EvaPérez-Elías, Maria JesúsHernández Quero, JoséRibas, Maria AngelsMartínez-Madrid, Onofre JFlores, JuanCrespo, ManelGutiérrez, FélixGarcía-Deltoro, MiguelImaz, ArkaitzOcampo, AntonioArtero, ArturoBlanco, FranciscoBernal, EnriquePasquau, JuanMínguez-Gallego, CarlosPérez, NúriaAiestarán, AintzaneParedes, Roger2016-08-092016-08-092014-11-02Garcia F, Poveda E, Pérez-Elías MJ, Quero JH, Ribas MA, Martínez-Madrid OJ, et al. Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study. J Int AIDS Soc. 2014; 17(4 Suppl 3):19520http://hdl.handle.net/10668/2320Journal Article; Oral presentation: The HIV Drug Therapy Glasgow Congress 2014INTRODUCTION In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. METHODS PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) <50 c/mL on stable ART during the previous 6 months, requiring an ART change due to toxicity, with no antiretroviral resistance to the ART started, and R5 HIV by proviral DNA genotypic tropism testing (defined as a G2P FPR >10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. RESULTS Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1). CONCLUSIONS Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure up to one year.enRecuento de linfocito CD4CiclohexanosARN Polimerasas dirigidas por ADNDislipidemiasExantemaInfecciones por VIHConsentimiento informadoInhibidores de integrasaHígadoPerdida de seguimientoNeoplasias pulmonaresEstudios prospectivosInfarto del miocardioProvirusARNADNTriazolesTropismoEspañaMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Cytological Techniques::Cell Count::Blood Cell Count::Leukocyte Count::Lymphocyte Count::CD4 Lymphocyte CountMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::CyclohexanesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::RNA Nucleotidyltransferases::DNA-Directed RNA PolymerasesMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Lipid Metabolism Disorders::DyslipidemiasMedical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Skin Diseases::ExanthemaMedical Subject Headings::Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV InfectionsMedical Subject Headings::Health Care::Health Care Economics and Organizations::Social Control, Formal::Human Rights::Patient Rights::Informed ConsentMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Integrase Inhibitors::HIV Integrase InhibitorsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxycytidine::Zalcitabine::LamivudineMedical Subject Headings::Anatomy::Digestive System::LiverMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Lost to Follow-UpMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung NeoplasmsMedical Subject Headings::Diseases::Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial InfarctionMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective StudiesMedical Subject Headings::Organisms::Viruses::ProvirusesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNAMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNAMedical Subject Headings::Geographicals::Geographic Locations::Europe::SpainMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Triazolesconference presentation25394029open access10.7448/IAS.17.4.195201758-2652PMC4224842