The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM.
AIDS
; 33(2): 237-246, 2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30557160
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), MVCâ+âemtricitabine (FTC), MVCâ+âtenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarateâ+âFTC], 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 1.8âlog10 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Reto
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Análise Química do Sangue
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Fármacos Anti-HIV
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Profilaxia Pré-Exposição
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Maraviroc
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article