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The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing PrEP Regimens in Men who have Sex with Men.

  • Author(s): McGowan, Ian
  • Wilkin, Timothy
  • Landovitz, Raphael J
  • Wu, Chunyuan
  • Chen, Ying
  • Marzinke, Mark A
  • Hendrix, Craig W
  • Richardson, Paul
  • Eshleman, Susan H
  • Andrade, Adriana
  • Chege, Wairimu
  • Anderson, Peter L
  • McCauley, Marybeth
  • Farley, Jason
  • Mayer, Kenneth H
  • Anton, Peter
  • Brand, Rhonda M
  • Cranston, Ross D
  • Gulick, Roy
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714572/pdf/nihms-1040660.pdf
No data is associated with this publication.
Abstract

OBJECTIVE:HIV Prevention Trials Network 069/AIDS Clinical Trials Group A5305 was a study of 48-week oral pre-exposure prophylaxis (PrEP) regimens in MSM and transgender women. A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral PrEP regimens [maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarate + FTC], and to determine whether ARV exposure was associated with ex-vivo suppression of HIV infection in colorectal explants. METHODS:C-C chemokine receptor type 5 (CCR5) genotype was characterized using PCR. At baseline and at Weeks 24, 48, and 49, GALT phenotype was characterized by flow cytometry, rectal biopsies were challenged with HIV-1BaL, and tissue and plasma pharmacokinetics were measured via mass spectrometry. RESULTS:Exposure to MVC was not associated with increased expression of CD4/CCR5 HIV target T cells. Significant ex-vivo viral suppression compared with baseline was seen at Weeks 24 and 48, ranging from 1.4 to 1.8 log10 for all study regimens except the MVC-alone arm which did not show statistically significant viral suppression at Week 48. Tissue concentrations of TFV, TFV-diphosphate, and FTC were correlated with viral suppression. CONCLUSION:MVC-containing HIV PrEP regimens did not increase GALT CD4 T-cell activation or the CD4/CCR5 phenotype. No virologic suppression was seen with MVC-alone at Week 48 compared with combination regimens, suggesting MVC monotherapy might be less effective than combination antiretroviral PrEP regimens.

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