Safety and Immunovirologic Outcomes with Maraviroc Combination Regimens in Patients with a History of Past Treatment Failures and Virologic Resistance in Brazil: An Open-Label, Multicenter Phase 3b Study

Abstract

Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, experience in regimens containing newer antiretroviral agents is limited. the primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. of 638 patients screened, 206 were treated and 125 completed the study. Approximately 70% were male; the mean age was 43.2 years. Most patients (65.0%) received an OBT combination of protease inhibitor plus nucleoside reverse transcriptase inhibitor. Adverse event (AE) and treatment-related AE incidence was 91.3% and 36.9%, respectively. the most common AEs were diarrhea, nasopharyngitis, and headache. Serious AEs and treatment-related serious AEs occurred in 16.5% and 4.4% of patients. Only eight patients (3.9%) discontinued due to AEs. Few AIDS-defining events were observed (4.9%). the proportion of patients with viral load 40% until week 48. At the end of treatment, 26.7% of patients had a viral load <400 copies/ml. Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/mu l. in conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.Pfizer, Inc.ViiV HealthcareABC, Fac Med, São Paulo, BrazilHosp Heliopolis, São Paulo, BrazilCtr Referencia & Treinamento DST AIDS, São Paulo, BrazilDay Hosp, STD AIDS, Mixed Unit 1, Reference Ctr 1, Brasilia, DF, BrazilInst Infectol Emilio Ribas, São Paulo, BrazilFMUSP, HC, Div Molestias Infecciosas & Parasitarias, São Paulo, BrazilUniv Fed Bahia, Hosp Univ Prof Edgard Santos, Salvador, BA, BrazilHosp Geral Nova Iguacu, Nova Iguacu, BrazilABC, Fac Med, Sau Paulo, BrazilFac Med Ribeirao Preto, Clin Hosp, Special Unit Infect Dis, Ribeirao Preto, BrazilUniv Fed Minas Gerais, Sch Med, Belo Horizonte, MG, BrazilPontificia Univ Catolica Parana, Curitiba, Parana, BrazilPontificia Univ Catolica Campinas, Hosp & Maternidade Celso Pierro, Campinas, SP, BrazilUniv Estadual Campinas, Hosp Clin, Campinas, SP, BrazilHosp Nereu Ramos, Florianopolis, SC, BrazilUniversidade Federal de São Paulo, Hosp São Paulo, São Paulo, BrazilHosp Mae de Deus, Porto Alegre, RS, BrazilPfizer Inc, New York, NY 10017 USAPfizer Brazil, São Paulo, BrazilUniversidade Federal de São Paulo, Hosp São Paulo, São Paulo, BrazilWeb of Scienc