title: 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 <400 copies/ml increased from 2.4% at baseline to 43.9% at week 8, remaining >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/μl. 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.
authors.affiliation: Faculdade de Medicina do ABC and Hospital Heliópolis, São Paulo, Brazil.
authors.forename: Juvencio
authors.initials: J
authors.lastname: Furtado
authors.forename: José V
authors.initials: JV
authors.lastname: Madruga
authors.forename: Eliana L
authors.initials: EL
authors.lastname: Bicudo
authors.forename: Margareth
authors.initials: M
authors.lastname: da Eira
authors.forename: Max I B F
authors.initials: MI
authors.lastname: Lopes
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Netto
authors.forename: Marília
authors.initials: M
authors.lastname: Santini-Oliveira
authors.forename: Olavo H M
authors.initials: OH
authors.lastname: Leite
authors.forename: Alcyone A
authors.initials: AA
authors.lastname: Machado
authors.forename: Unaí
authors.initials: U
authors.lastname: Tupinambas
authors.forename: José L
authors.initials: JL
authors.lastname: de Andrade Neto
authors.forename: Maria P J S
authors.initials: MP
authors.lastname: Lima
authors.forename: Rogério de Jesus
authors.initials: Rde J
authors.lastname: Pedro
authors.forename: Antônio F B
authors.initials: AF
authors.lastname: Miranda
authors.forename: David S
authors.initials: DS
authors.lastname: Lewi
authors.forename: Breno R
authors.initials: BR
authors.lastname: Santos
authors.forename: Simon
authors.initials: S
authors.lastname: Portsmouth
authors.forename: Dalia B
authors.initials: DB
authors.lastname: Wajsbrot
authors.forename: Lourenia M
authors.initials: LM
authors.lastname: Cassoli
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D001938:Brazil; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000009:adverse effects* / Q000627:therapeutic use*; D000069454:Darunavir; D004359:Drug Therapy, Combination; D005260:Female; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D014230:Triazoles; D000068898:Raltegravir Potassium; D000077592:Maraviroc; D000069454:Darunavir