Pharmacokinetics and Pharmacodynamics of DMPA With HIV PrEP
Condition: HIV/AIDS; Contraception
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This study is a biphasic steady state pharmacokinetic and pharmacodynamic study of TFV and
      FTC in healthy women comparing the drug levels and activity in the absence (first phase) and
      then the presence (second phase) of DMPA. The investigators will recruit 12 healthy women
      aged 18-45 who are HIV-negative and at low risk for acquiring HIV.
    

Detailed description: 
      The investigators hypothesize that a drug interaction exists between DMPA and
      tenofovir/emtricitabine, such that levels of tenofovir (TFV) and emtricitabine (FTC) in
      cervicovaginal fluid, rectal fluid, and blood plasma, and levels of the active metabolites of
      TFV and FTC in cervical tissue and peripheral blood mononuclear cells will be significantly
      lower when women are using DMPA than when they are using no hormonal contraception. The
      investigators secondarily hypothesize that ex vivo HIV replication will be less suppressed in
      cervical tissue and cervicovaginal fluid when women are using the co-formulated pre-exposure
      prophylaxis oral pill containing tenofovir disoproxil fumarate (TDF), the prodrug of
      tenofovir, and FTC concurrently with the contraceptive injection DMPA as compared to when
      they are on TDF/FTC alone. This study is a biphasic steady state pharmacokinetic and
      pharmacodynamic study of TFV and FTC in healthy women comparing the drug levels and activity
      in the absence (first phase) and then the presence (second phase) of DMPA. The investigators
      will recruit 12 healthy women aged 18-45 who are HIV-negative and at low risk for acquiring
      HIV. Participants will take TDF/FTC for 14 days, after which drug levels will be measured and
      DMPA administered. After at least a 2 week washout period for TDF/FTC, participants will
      again take TDF/FTC for 14 days, and drug levels will be measured again. HIV replication
      activity will also be measured in cervicovaginal fluid and cervical tissue at baseline before
      starting TDF/FTC, after 14 days of TDF/FTC, and then after the second 14 days of TDF/FTC in
      the presence of DMPA.
    

Intervention name(s): tenofovir/emtricitabine; DMPA
Intervention type(s): Combination Product; Drug
Intervention description(s): At the enrollment visit, participants will be given a 14-day supply of tenofovir/emtricitabine 200mg/300mg to take once daily for 14 days. Drug concentrations will be measured as outlined in the outcomes section at the end of the two week period. The tenofovir/emtricitabine 200mg/300mg course will be repeated approximately 2 to 6 weeks later to allow washout of tenofovir/emtricitabine.; After completion of the first 14 day course of tenofovir/emtricitabine depot medroxyprogesterone acetate 150 mg will be administered as intramuscular injection.
Other intervention name(s): Truvada®; Depot-Medroxyprogestereone Acetate
Intervention MeSH terms: Tenofovir; Emtricitabine; Medroxyprogesterone Acetate; Medroxyprogesterone
Intervention model: Sequential Assignment
Intervention model description: This is a biphasic steady state pharmacokinetic and pharmacodynamic study of healthy women to evaluate the concentrations and activity of tenofovir and emtricitabine in different compartments before and after the administration of DMPA. Each participant will receive the study medications in the same order, i.e. TDF/FTC alone for 14 days followed by TDF/FTC for 14 days after having received DMPA.
Masking: None (Open Label)
Primary purpose: Other