Pharmacokinetic and Pharmacodynamic Impacts of Depot Medroxyprogesterone Acetate Use on HIV Pre-exposure Prophylaxis in Women

被引:4
作者
Tarleton, Jessica [1 ]
Chen, Beatrice A. [1 ,2 ]
Meyn, Leslie A. [1 ]
Hendrix, Craig W. [3 ]
Marzinke, Mark A. [3 ]
Achilles, Sharon L. [1 ,2 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA
[2] Magee Womens Res Inst, Pittsburgh, PA USA
[3] Johns Hopkins Univ, Dept Med Clin Pharmacol, Sch Med, Baltimore, MD USA
关键词
DMPA; PrEP; tenofovir; emtricitabine; TENOFOVIR DISOPROXIL FUMARATE; DRUG TRANSPORTERS; EMTRICITABINE; PHARMACOLOGY; INFECTION; CELLS; CONTRACEPTIVES; EFFICACY; TISSUES;
D O I
10.1097/QAI.0000000000002421
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Depot medroxyprogesterone acetate (DMPA) is a commonly used contraceptive in areas where use of tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis (PrEP) is increasing. Objectives: We aimed to investigate the impact of DMPA on PrEP drug pharmacokinetics and pharmacodynamics in women using PrEP before and after DMPA administration. Methods: In this pilot study, 12 HIV-negative women ages 18-45 underwent biological sample collection at 3 time points: before study drug, after 2 weeks of daily PrEP use alone, and after 2 weeks of daily PrEP and concomitant DMPA use. We measured drug and drug metabolites in plasma, peripheral blood mononuclear cells, cervicovaginal fluid, cervical tissue, and rectal fluid after each 2-week course of PrEP. We measured HIV replication ex vivo in genital tissue biopsies and innate anti-HIV activity in cervicovaginal fluid before PrEP and after both courses. We compared drug concentrations after PrEP alone to after PrEP and DMPA in the same participant using Wilcoxon signed-rank tests. We used mixed effects linear regression models to compare pharmacodynamic measures for each participant at predrug baseline, after PrEP alone, and after PrEP and DMPA. Results: We found no significant differences in PrEP drug and drug metabolite concentrations in any compartment during concomitant DMPA use compared with use of PrEP alone, except for a reduction in emtricitabine concentration in cervical tissue. We found no difference in HIV replication in cervical tissue or anti-HIV activity in cervicovaginal fluid during concomitant DMPA and PrEP use compared with during PrEP use alone. Conclusions: Concomitant use of DMPA does not clinically alter pharmacokinetics or pharmacodynamics of PrEP in women. These data support the safety of DMPA use in women using PrEP.
引用
收藏
页码:182 / 188
页数:7
相关论文
共 32 条
  • [1] The complexity of contraceptives: understanding their impact on genital immune cells and vaginal microbiota
    Achilles, Sharon L.
    Hillier, Sharon L.
    [J]. AIDS, 2013, 27 : S5 - S15
  • [2] Cytokine and sex hormone effects on zidovudine- and lamivudine-triphosphate concentrations in vitro
    Anderson, Peter L.
    King, Tracy
    Zheng, Jia-Hua
    MaWhinney, Samantha
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2008, 62 (04) : 738 - 745
  • [3] Determination of nucleoside analog mono-, di-, and tri-phosphates in cellular matrix by solid phase extraction and ultra-sensitive LC-MS/MS detection
    Bushman, Lane R.
    Kiser, Jennifer J.
    Rower, Joseph E.
    Klein, Brandon
    Zheng, Jia-Hua
    Ray, Michelle L.
    Anderson, Peter L.
    [J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2011, 56 (02) : 390 - 401
  • [4] Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk
    Butler, Ailsa R.
    Smith, Jennifer A.
    Polis, Chelsea B.
    Gregson, Simon
    Stanton, David
    Hallett, Timothy B.
    [J]. AIDS, 2013, 27 (01) : 105 - 113
  • [5] Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy
    Chappell, Catherine A.
    Lamorde, Mohammed
    Nakalema, Shadia
    Chen, Beatrice A.
    Mackline, Hope
    Riddler, Sharon A.
    Cohn, Susan E.
    Darin, Kristin M.
    Achilles, Sharon L.
    Scarsi, Kimberly K.
    [J]. AIDS, 2017, 31 (14) : 1965 - 1972
  • [6] A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine
    Cottrell, Mackenzie L.
    Yang, Kuo H.
    Prince, Heather M. A.
    Sykes, Craig
    White, Nicole
    Malone, Stephanie
    Dellon, Evan S.
    Madanick, Ryan D.
    Shaheen, Nicholas J.
    Hudgens, Michael G.
    Wulff, Jacob
    Patterson, Kristine B.
    Nelson, Julie A. E.
    Kashuba, Angela D. M.
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2016, 214 (01) : 55 - 64
  • [7] HIV-1 Infection of Female Genital Tract Tissue for Use in Prevention Studies
    Dezzutti, Charlene S.
    Uranker, Kevin
    Bunge, Katherine E.
    Richardson-Harman, Nicola
    Macio, Ingrid
    Hillier, Sharon L.
    [J]. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2013, 63 (05) : 548 - 554
  • [8] Performance of Swabs, Lavage, and Diluents to Quantify Biomarkers of Female Genital Tract Soluble Mucosal Mediators
    Dezzutti, Charlene S.
    Hendrix, Craig W.
    Marrazzo, Jeanne M.
    Pan, Zhenyu
    Wang, Lei
    Louissaint, Nicolette
    Kalyoussef, Sabah
    Torres, N. Merna
    Hladik, Florian
    Parikh, Urvi
    Mellors, John
    Hillier, Sharon L.
    Herold, Betsy C.
    [J]. PLOS ONE, 2011, 6 (08):
  • [9] Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men.
    Grant, Robert M.
    Lama, Javier R.
    Anderson, Peter L.
    McMahan, Vanessa
    Liu, Albert Y.
    Vargas, Lorena
    Goicochea, Pedro
    Casapia, Martin
    Guanira-Carranza, Juan Vicente
    Ramirez-Cardich, Maria E.
    Montoya-Herrera, Orlando
    Fernandez, Telmo
    Veloso, Valdilea G.
    Buchbinder, Susan P.
    Chariyalertsak, Suwat
    Schechter, Mauro
    Bekker, Linda-Gail
    Mayer, Kenneth H.
    Kallas, Esper Georges
    Amico, K. Rivet
    Mulligan, Kathleen
    Bushman, Lane R.
    Hance, Robert J.
    Ganoza, Carmela
    Defechereux, Patricia
    Postle, Brian
    Wang, Furong
    McConnell, J. Jeff
    Zheng, Jia-Hua
    Lee, Jeanny
    Rooney, James F.
    Jaffe, Howard S.
    Martinez, Ana I.
    Burns, David N.
    Glidden, David V.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (27) : 2587 - 2599
  • [10] Preexposure prophylaxis is efficacious for HIV-1 prevention among women using depot medroxyprogesterone acetate for contraception
    Heffron, Renee
    Mugo, Nelly
    Were, Edwin
    Kiarie, James
    Bukusi, Elizabeth A.
    Mujugira, Andrew
    Frenkel, Lisa M.
    Donnell, Deborah
    Ronald, Allan
    Celum, Connie
    Baeten, Jared M.
    [J]. AIDS, 2014, 28 (18) : 2771 - 2776