title: Safety, efficacy and indications of prescription of maraviroc in clinical practice: Factors associated with clinical outcomes.
abstract: Maraviroc is approved for treatment-experienced HIV+ adults in twice-daily administration. Limited data are available on safety, efficacy and use in routine clinical practice, outside of restrictive clinical trials. This retrospective multicenter (27 centers) study included 667 subjects starting a regimen with maraviroc. The primary endpoint was plasma HIV-RNA <50copies/mL and CD4(+) cell count change at 48 and 96weeks (FDA snapshot analysis). 94.4% had CCR5 tropism (58.3% Trofile™, 29.2% population genotype, and 12% genotyping proviral DNA). Half of the subjects received the drug in scenarios or dosages outside the initial approval. Maraviroc was prescribed for salvage in 346 (51.9%) individuals, as a switch strategy due to toxicity in 135 (38.7%), for immune discordance in 75 (11.2%), and for simplification in 48 (7.2%). After salvage therapy, 223 (64.5%) subjects had HIV-RNA <50copies/mL at 48weeks, and 178 (51.4%) at 96weeks. Darunavir/r was included in 224 (64.7%) subjects and associated with higher rates of virological and immunologic efficacy (p<0.001). In multivariate analysis MSM (OR 2.25; 95%CI 1.29-3.94) and baseline HIV-RNA <100,000copies/mL (OR 1.96; 1.06-3.70) were associated with virological suppression. An increase in CD4(+) counts was seen at 48 and 96weeks in subjects with immune discordance (p<0.001). Maraviroc was used once-daily in 142 (21.3%) subjects overall, and 68 (57.4%) in switch/simplification. No new safety signals were identified. Besides in salvage regimens, maraviroc was frequently used in switch due to toxicity, simplification, and immune discordance. The efficacy in salvage in clinical practice was higher than in phase III clinical trials, likely due to availability of new active drugs in the regimen. These results increase our understanding of the efficacy, safety, and conditions of prescription of maraviroc beyond the initial registrational trials and the early manufacturer pharmacovigilance programs.
authors.affiliation: HIV Unit and "Lluita contra la SIDA" Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Spain. Electronic address: jmllibre@flsida.org.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.affiliation: Hospital Reina Sofía/IMIBIC, Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Hospital Clinic IDIBAPS, Barcelona, Spain.
authors.forename: Jhon F
authors.initials: JF
authors.lastname: Rojas
authors.affiliation: Hospital General de Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Garcia Del Toro
authors.affiliation: HIV Unit and "Lluita contra la SIDA" Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Herrero
authors.affiliation: Clinical Biostatistics Unit, Hospital Ramón y Cajal, CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Arroyo
authors.affiliation: Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Pasquau
authors.affiliation: Hospital Universitario de Elche, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.affiliation: Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Crespo
authors.affiliation: Hospital San Pedro CIBIR, Logroño, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Blanco
authors.affiliation: Infectious Diseases, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc
keywords: Antiretroviral treatment; CCR5 antagonists; CCR5 tropism; Immune discordance; Maraviroc; Salvage treatment