TY - JOUR
T1 - Interaction of Depot Medroxyprogesterone Acetate and Tenofovir Disoproxil Fumarate/Emtricitabine on Peripheral Blood Mononuclear Cells and Cervical Tissue Susceptibility to HIV Infection and Pharmacokinetics
AU - Coleman, Jenell S.
AU - Diniz, Clarissa P.
AU - Fuchs, Edward
AU - Marzinke, Mark A.
AU - Aung, Wutyi
AU - Bakshi, Rahul P.
AU - Farzadegan, Homayoon
AU - Bream, Jay
AU - Nilles, Tricia L.
AU - Hudson, Sherry
AU - Bumpus, Namandje
AU - Schwartz, George J.
AU - Rosenblum, Michael A.
AU - Rooney, James F.
AU - Hendrix, Craig W.
N1 - Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background:Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is highly effective in reducing HIV acquisition in women. We sought to determine the impact of DMPA on F/TDF pharmacokinetics and pharmacodynamics.Methods:Twelve healthy premenopausal cisgender women were enrolled and each completed 4 sequential conditions: (1) baseline, (2) steady-state F/TDF alone, (3) steady-state F/TDF + DMPA, and (4) DMPA alone. Assessments included clinical, pharmacokinetic, viral infectivity (ex vivo challenge of peripheral blood mononuclear cells by X4- and R5-tropic green fluorescent protein pseudoviruses and cervical tissue by HIVBaL), endocrine, immune cell phenotyping, and renal function.Results:Compared with baseline, F/TDF (± DMPA) significantly decreased both %R5- and X4-infected CD4 T cells and F/TDF + DMPA decreased cervical explant p24 (all P < 0.05). The %R5- and X4-infected CD4 T cells were higher during DMPA alone than during F/TDF periods and lower than baseline (not statistically significant). Cervical explant p24 fell between baseline and F/TDF values (not statistically significant). There were neither statistically significant differences in F/TDF pharmacokinetics, including total or renal clearance of either antiviral drug, nor changes in glomerular filtration rate with the addition of DMPA. There were few immune cell phenotypic differences across conditions.Conclusions:F/TDF decreased HIV infection in both challenge assays, whereas DMPA alone did not enhance HIV infection in either challenge assay. DMPA did not alter F/TDF pharmacokinetics or renal function.
AB - Background:Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is highly effective in reducing HIV acquisition in women. We sought to determine the impact of DMPA on F/TDF pharmacokinetics and pharmacodynamics.Methods:Twelve healthy premenopausal cisgender women were enrolled and each completed 4 sequential conditions: (1) baseline, (2) steady-state F/TDF alone, (3) steady-state F/TDF + DMPA, and (4) DMPA alone. Assessments included clinical, pharmacokinetic, viral infectivity (ex vivo challenge of peripheral blood mononuclear cells by X4- and R5-tropic green fluorescent protein pseudoviruses and cervical tissue by HIVBaL), endocrine, immune cell phenotyping, and renal function.Results:Compared with baseline, F/TDF (± DMPA) significantly decreased both %R5- and X4-infected CD4 T cells and F/TDF + DMPA decreased cervical explant p24 (all P < 0.05). The %R5- and X4-infected CD4 T cells were higher during DMPA alone than during F/TDF periods and lower than baseline (not statistically significant). Cervical explant p24 fell between baseline and F/TDF values (not statistically significant). There were neither statistically significant differences in F/TDF pharmacokinetics, including total or renal clearance of either antiviral drug, nor changes in glomerular filtration rate with the addition of DMPA. There were few immune cell phenotypic differences across conditions.Conclusions:F/TDF decreased HIV infection in both challenge assays, whereas DMPA alone did not enhance HIV infection in either challenge assay. DMPA did not alter F/TDF pharmacokinetics or renal function.
KW - GFP pseudovirus
KW - HIV pre-exposure prophylaxis
KW - depot medroxyprogesterone acetate
KW - emtricitabine
KW - ex vivo HIV challenge
KW - tenofovir
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U2 - 10.1097/QAI.0000000000003113
DO - 10.1097/QAI.0000000000003113
M3 - Article
C2 - 36305827
AN - SCOPUS:85143644857
SN - 1525-4135
VL - 92
SP - 89
EP - 96
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 1
ER -