title: Muscle symptoms and creatine phosphokinase elevations in patients receiving raltegravir in clinical practice: Results from the SCOLTA project long-term surveillance.
abstract: Muscle alterations ranging from asymptomatic creatine phosphokinase (CPK) increases to rhabdomyolysis and central nervous system (CNS) symptoms have been reported in patients receiving raltegravir. Muscle symptoms and CPK increases were investigated in a cohort of HIV-infected patients receiving raltegravir-based antiretroviral therapy, and possible associated predictors were evaluated. The SCOLTA Project is a prospective, observational, multicentre study created to assess the incidence of adverse events in patients receiving new antiretroviral drugs in clinical practice. In total, 496 HIV-infected patients were enrolled [333 (67.1%) male]. CDC stage was C in 196 patients (39.5%). Mean age at enrolment was 45.9 ± 9.3 years. Median follow-up was 21 months. Twenty-six patients (5.2%) reported muscle symptoms (16 muscle pain and 17 weakness; 7 had both). Of 342 patients with normal baseline CPK values, 72 (21.1%) had a CPK increase. Seven patients (1.4%) discontinued raltegravir because of muscular events (three for muscle pain/weakness and four CPK increases). No cases of rhabdomyolysis were observed. Patients with muscle symptoms were more frequently receiving in their regimen than those not receiving atazanavir (P=0.04) and were more likely to also report CNS symptoms (P<0.0001). Significant predictors of muscle symptoms were CNS symptoms and use of atazanavir. Female sex was associated with a reduced risk of CPK increase. In conclusion, muscle symptoms and CPK elevations occurred frequently and caused most discontinuations due to adverse events. Their monitoring in patients receiving raltegravir should be considered, especially when co-administered with atazanavir or when CNS symptoms are also present.
authors.affiliation: Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy. Electronic address: giordano.madeddu@uniss.it.
authors.forename: Giordano
authors.initials: G
authors.lastname: Madeddu
authors.affiliation: Unit of Infectious Diseases, Santa Maria Hospital, Perugia, Italy.
authors.forename: Giuseppe V L
authors.initials: GV
authors.lastname: De Socio
authors.affiliation: epi2004, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ricci
authors.affiliation: Unit of Infectious Diseases, Busto Arsizio Hospital, Busto Arsizio, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Quirino
authors.affiliation: Department of Infectious Diseases, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Orofino
authors.affiliation: Department of Infectious Diseases, L. Sacco Hospital, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Carenzi
authors.affiliation: Department of Infectious Diseases, L. Sacco Hospital, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Franzetti
authors.affiliation: Department of Infectious Diseases, Pescara Hospital, Pescara, Italy.
authors.forename: Giustino
authors.initials: G
authors.lastname: Parruti
authors.affiliation: Unit of Infectious Diseases, Careggi Hospital, Firenze, Italy.
authors.forename: Canio
authors.initials: C
authors.lastname: Martinelli
authors.affiliation: Unit of Infectious Diseases, Santa Maria Annunziata Hospital, Firenze, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vichi
authors.affiliation: Unit of Infectious Diseases, Galliera Hospital, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Penco
authors.affiliation: Unit of Infectious Diseases, San Remo Hospital, San Remo, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dentone
authors.affiliation: Unit of Infectious Diseases, ARNAS Garibaldi Hospital, Catania, Italy.
authors.forename: Benedetto Maurizio
authors.initials: BM
authors.lastname: Celesia
authors.affiliation: Infectious Disease Clinic, University of Bari, Bari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Maggi
authors.affiliation: III Department of Infectious Diseases, L. Spallanzani Hospital, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Libertone
authors.affiliation: Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bagella
authors.affiliation: Infectious Diseases, IRCCS San Martino Hospital, University of Genoa, Genoa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.affiliation: Unit of Infectious Diseases, A. Manzoni Hospital, Lecco, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonfanti
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D003402:Creatine Kinase / Q000097:blood*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000139:chemically induced* / Q000453:epidemiology; D063806:Myalgia / Q000139:chemically induced* / Q000453:epidemiology; D009842:Oligopeptides / Q000627:therapeutic use; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000009:adverse effects* / Q000627:therapeutic use; D000068898:Raltegravir Potassium
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate; D003402:Creatine Kinase
keywords: Creatine phosphokinase elevations; Muscle symptoms; Raltegravir