Abstract
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 1.8log10 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.
Original language | English (US) |
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Pages (from-to) | 237-246 |
Number of pages | 10 |
Journal | AIDS |
Volume | 33 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2019 |
Keywords
- HIV
- MSM
- clinical trial
- explant challenge
- maraviroc
- pharmacodynamic
- pharmacokinetic
- pre-exposure prophylaxis
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases