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.
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.
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.
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.
aDepartment of Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania
bDivision of Infectious Diseases, Weill Cornell Medicine, New York, New York
cDivision of Infectious Diseases, Department of Medicine, Center for AIDS Research and Education & Center for HIV Prevention, David Geffen School of Medicine at UCLA, Los Angeles, California
dProtocol Statistician, FHCRC-SCHARP, Seattle, Washington
eDivision of Clinical Pharmacology, Department of Pathology
fDivision of Clinical Pharmacology
gDivision of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
hDivision of AIDS, Clinical Prevention Research Branch, Prevention Sciences Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
iSkaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado
jFHI 360, Washington, District of Columbia
kDepartment of Medicine, Fenway Health, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
lDivision of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Correspondence to Ian McGowan, MD, PhD, FRCP, Chief Scientific Officer, Orion Biotechnology 343 Preston St, Ottawa, Ontario, K1S 1N4, Canada. Tel: +1 412 352 5270; e-mail: firstname.lastname@example.org
Received 15 December, 2017
Accepted 8 July, 2018