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.

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.

Inclusion Criteria:

• Women aged 18-45 at screening
• In general good health and without any clinically significant systemic disease by history and per investigator judgement
• HIV negative at screening
• Heterosexually abstinent, consistent use of condoms, or female or male partner sterilization
• Currently having regular menstrual cycles (defined as cycles lasting 21-35 days by participant report)
• Agree not to participate in any other clinical trials involving drugs or medical devices during the study period
• Willing to comply with the study protocol

Exclusion Criteria:

• Currently or recently pregnant or breastfeeding (defined as pregnancy or breastfeeding in the last 3 months)
• Desiring pregnancy in the next 9 months
• Use of copper intrauterine device or other method of hormonal contraception
• Status post hysterectomy and/or bilateral oophorectomy
• Positive test for Hepatitis B surface antigen at screening
• Positive for Neisseria gonorrhea, Chlamydia trachomatis, or Trichomonas vaginalis at screening
• Positive syphilis screening test at screening
• Symptomatic bacterial vaginosis, defined as vaginal symptoms with Nugent score ≥ 7. (If symptomatic bacterial vaginosis is treated at screening and asymptomatic at enrollment, the participant may enroll.)
• Renal impairment (defined as creatinine clearance <60 ml/minute)
• Known bleeding disorder
• Daily use of NSAIDs
• Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants, antifungals, antivirals, antiretrovirals, or other drugs known to prolong bleeding and/or clotting,
• Use of DMPA in the 6 months prior to screening
• Use of other hormonal contraception (including any contraceptive pill, patch, ring, implant, or levonorgestrel intrauterine device) in the 28 days prior to screening.
• Surgery requiring inpatient admission, or any abdominal surgery <30 days prior to enrollment
• Recreational or non-medical injection drug use in the 12 months prior to screening
• In a sexual relationship with a partner known to be HIV-positive or at high-risk of HIV (e.g. known recreational injection drug user, incarcerated in the 12 months prior to screening, etc.)
• Has any other condition that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, or complicate the interpretation of the study outcome data, or otherwise interfere with achieving the study objectives