The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM. Academic Article uri icon



  • 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.


  • 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 M

publication date

  • February 1, 2019



  • Anti-HIV Agents
  • Blood Chemical Analysis
  • Maraviroc
  • Pre-Exposure Prophylaxis
  • Rectum


PubMed Central ID

  • PMC6714572

Scopus Document Identifier

  • 85058903796

Digital Object Identifier (DOI)

  • 10.1097/QAD.0000000000002038

PubMed ID

  • 30557160

Additional Document Info


  • 33


  • 2