title: A prospective evaluation of maraviroc administration in patients with advanced HIV disease and multiple comorbidities: focus on efficacy and tolerability issues.
abstract: In our HIV outpatient centre where over 1,200 patients are followed, maraviroc as an entry inhibitor was introduced in 2010. We aimed to assess the background, the therapeutic challenges and the prospective monitoring of all patients treated with a combination antiretroviral therapy (cART) including maraviroc. Sixty-six patients started a maraviroc-containing cART with a history of HIV infection lasting 13.9±10.7 years. This interim analysis presents patients who had at least 12 (mean 16.9±12.8) months of follow-up. One to 17 previous cART changes prompted the introduction of maraviroc in rescue regimens in the great majority of patients considered (53 of 66); in 13 cases, maraviroc was given to patients with advanced HIV disease and no immune recovery after 2-3 years of a virologically-effective cART. The most frequent companion antiretroviral agents were: darunavir/ritonavir (51 cases), raltegravir (49 subjects), and etravirine (36 cases). The most common underlying conditions were: AIDS (41 cases), liver cirrhosis (21), AIDS-related or other malignancies (20 cases), major cardiovascular events (18 cases), osteonecrosis and haemodialysis-treated kidney failure (3 cases each). A chronic HCV and HBV hepatitis were of concern in 25 and 13 patients. The addition of maraviroc added favourably to clinical-laboratory markers of HIV disease progression, and those of comorbid conditions. HIV viraemia became (or remained) undetectable in 55 patients of 66 (83.3%). An improvement in CD4+ count was observed in all 66 patients, based on a mean 24.9±19.2% increase versus baseline, paralleled by an improvement in mean absolute CD4+ count of 134.7±121.1 cells/μL. A tendency towards an increased mean and peak CD4+ count was observed in the subgroup receiving a maraviroc-raltegravir-based cART. As no clinical-laboratory adverse events attributable to maraviroc occurred, nobody discontinued the study drug. Only mild-transient gastrointestinal disturbances, fatigue and anorexia, were reported during maraviroc administration, but their relationship with the study drug was difficult to assess because of the multiple comorbidities and polypharmacy. Our preliminary experience with maraviroc, even considering the limits of the proportionally reduced sample, the patients' salvage stage of advanced disease and the related-unrelated morbidities, underlines its excellent efficacy and safety profile.
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredi
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calza
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Marinacci
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cascavilla
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Colangeli
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Salvadori
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Martelli
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Appolloni
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Puggioli
authors.affiliation: Infectious Diseases, Alma Mater Studiorum University of Bologna, S. Orsola-Malpighi Hospital; Hospital Pharmacy, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D015897:Comorbidity; D003510:Cyclohexanes / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D019562:Viral Load / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc