Immunologic Effects of Maraviroc in HIV-Infected Patients with Severe CD4 Lymphopenia Starting Antiretroviral Therapy: A Sub-Study of the CADIRIS Trial

• Main Authors: Pablo Francisco Belaunzarán-Zamudio (Author), Livio Azzoni (Author), David H. Canaday (Author), Yanink N. Caro-Vega (Author), Brian Clagget (Author), Mohammed S Rassool (Author), Benigno Rodriguez (Author), Ian Sanne (Author), Irini Sereti (Author), Juan G. Sierra-Madero (Author), Michael M. Lederman (Author)
• Format: Book
• Published: Case Western Reserve University, 2017-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Background:  We aimed to describe the mechanisms of immunological recovery and the effects of blocking CCR5 in patients starting ART with advanced HIV-infection. Methods: Sub-study of a randomized, double-blind, clinical trial where patients starting ART with CD4 counts <100cells/uL received maraviroc or placebo. CD4 and CD8 maturation phenotypes, PD-1 and CCR5 expression, and activation indices were characterized at weeks 0, 4, 12, 24 and 48. CD4 and CD8 reactivity with peptides of CMV, MTb and with Staphylococcal enterotoxin B (SEB) was assessed by intracellular expression of IFNγ, TNFα and CD40 ligand at weeks 0, 4 and 12 of ART. Results: Forty patients were studied (Maraviroc=22; placebo=18). Sustained increases in CD8 were observed in the maraviroc arm. Significant, increases in the proportions of circulating CCR5+ CD4 and CD8; in central memory and effector memory CD8; and in the proportion of activated CD4 and CD8 were observed at week 4 in the maraviroc arm. T cell responses to CMV, MTb and SEB did not differ by treatment arms.  Conclusions: The higher increases of CCR5+ and activated CD4 and CD8 in circulation without affecting CD4 recovery or antigen-specific T-cell responses strongly suggests an increased retention in circulation of CCR5+ cells due to maraviroc.

Item Description

2469-2964
10.20411/pai.v2i2.181