Pharmacokinetic Interactions Between DMPA and LPV/r Among HIV-Infected Women
Condition: HIV-1 Infection
Intervention: depo-medroxyprogesterone acetate
Intervention description: At study entry/ Day 0, participants will receive Depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
Intervention MeSH terms: Medroxyprogesterone Acetate; Medroxyprogesterone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: Female
Minimum age: 13 Years
Healthy volunteers: No

Summary:

      This study was done to look at the level of Depo-Provera, an injectable birth control, in the
      blood to see whether it is affected by the anti-HIV drug Kaletra (lopinavir/ritonavir
      [LPV/r]). It is not known whether taking Depo-Provera together with Kaletra changes the
      amount of Kaletra in blood. Therefore, this study also looked at the levels of HIV and
      Kaletra before and after receiving a shot of Depo-Provera. This study evaluated the safety of
      Depo-Provera and Kaletra when they are used together. In addition to what is stated above,
      this study also explored any effect of Depo-Provera on the immune system.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection

          -  Documentation of plasma HIV-1 RNA </= 400 copies/mL within 30 days prior to study
             entry.

          -  Last menstrual period </= 35 days prior to study entry.

          -  If last menstrual period >35 days prior to study entry, serum follicle-stimulating
             hormone (FSH) must be </= 40 Milli-International units per Milliliter (MIU/mL)

          -  Stable anti-retroviral (ARV) regimen consisting of BID LPV/r plus 2 or more nucleoside
             reverse transcriptase inhibitors (NRTIs) for at least 30 days if postpartum or for at
             least the previous 14 days if on a previously stable antiretroviral regimen without
             modifications prior to study entry

          -  Cluster of Differentiation 4 (CD4+) cell count ≥200 cells/mm^3 within 30 days prior to
             study entry

          -  Certain laboratory values within 30 days prior to study entry

          -  Premenopausal females with normal ovarian function

          -  Negative serum or urine-Human Chorionic Gonadotropin (HCG) pregnancy test within 72
             hours prior to study entry

          -  All subjects must agree not to participate in a conception process (e.g., active
             attempt to become pregnant or in vitro fertilization) for the duration of the
             study.Subjects of reproductive potential, who are participating in sexual activity
             that could lead to pregnancy, must agree to use an additional reliable method of
             contraception while in the study.

          -  Ability and willingness to give written informed consent

          -  Documentation of Pap smear within one year prior to study entry.

          -  Documentation of hepatitis B (surface antigen) and hepatitis B (core antibody) and
             hepatitis C (antibody) status prior to study entry.

          -  Documentation of varicella-zoster virus (VZV) status by history of varicella or herpes
             zoster, or history of varicella or herpes zoster vaccination or documentation of
             anti-VZV antibodies.

          -  Willingness to abstain from alcohol 24 hours prior to and during the 10-hour
             pharmacokinetic (PK) specimen draws.

          -  Willingness to abstain from any grapefruit product or supplement for 24 hours prior to
             entry and for the duration of the study.

        Exclusion Criteria:

          -  Received DMPA within 180 days prior to study entry.

          -  Received other hormonal therapies within the 30 days prior to study entry.

          -  Concurrent dual nucleoside therapy of zidovudine (ZDV) and stavudine (d4T) within 30
             days prior to study entry.

          -  Use of any prohibited medications within 30 days prior to study entry. Prohibited
             Medications were:

               -  amiodarone (Cordarone)

               -  astemizole (Hismanal)

               -  bepridil (Vascor)

               -  carbamazepine (Tegretol)

               -  cisapride (Propulsid)

               -  clarithromycin (Biaxin)

               -  cyclosporine (Sandimmune, Neoral)

               -  dihydroergotamine (Migranal and others)

               -  ergotamine (Ergostat, Gotamine, and others)

               -  erythromycin (E-mycin, erythromycin ethylsuccinate (EES) and others)

               -  flecainide (Tambocor)

               -  glucocorticoids

               -  Hypericum perforatum (St. John's wort)

               -  itraconazole (Sporanox)

               -  ketoconazole (Nizoral)

               -  lovastatin (Mevacor)

               -  midazolam (Versed)

               -  nefazadone (Serzone)

               -  phenobarbital (Luminal)

               -  phenytoin (Dilantin)

               -  pimozide (Orap)

               -  pioglitazone (Actos)

               -  propafenone (Rythmol)

               -  propofol (Diprivan)

               -  quinidine (Quinidex)

               -  rifabutin (Mycobutin)

               -  rifampin (Rifadin, Rifamate, Rifater, Rimactane)

               -  rosiglitazone (Avandia)

               -  simvastatin (Zocor)

               -  tacrolimus (Prograf)

               -  terfenadine

               -  ticlopidine (Ticlid), and

               -  triazolam (Halcion)

          -  Breastfeeding.

          -  Less than 30 days postpartum at study entry.

          -  Bilateral oophorectomy.

          -  Hypersensitivity to DMPA, MPA, or any of the other ingredients in DMPA.

          -  More than a 50% change in tobacco smoking within the 30 days prior to study entry or
             plans to significantly change tobacco use during the study.

          -  Invasive cancer of the reproductive tract; known or suspected malignancy of the
             breast, or known increased risk for breast cancer; undiagnosed vaginal bleeding; liver
             tumors; or serious ocular disorders at any time prior to study entry.

          -  Uncontrolled hypothyroidism or hyperthyroidism within 30 days of study entry.

          -  Acute infections or other opportunistic diseases requiring medication within 14 days
             prior to study entry.

          -  Receipt of any immunizations within 2 weeks prior to enrollment.

          -  Use of any immunosuppressant medication including systemic corticosteroids within 30
             days prior to study entry.

          -  Chronic immunosuppressive conditions other than HIV.

          -  Initiated, discontinued, or changed doses of drugs that are cytochrome P450 3A4
             (CYP3A4) substrates within 30 days of study entry.

          -  History of deep venous thrombosis or pulmonary emboli.