Protease Inhibitors and Combined Oral Contraceptive Pharmacokinetics and Pharmacodynamics
Condition: Contraception; HIV
Intervention: Levonorgestrel and Ethinyl Estradiol
Intervention description: All participants will take a combined oral contraceptive containing 150mcg levonorgestrel and 30mcg ethinyl estradiol for 21 days. Pharmacokinetics and pharmacodynamics will be compared between participants using antiretroviral regimens including ritonavir-boosted protease inhibitors and those using regimens that do not interact with oral contraceptives.
Intervention MeSH terms: Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Estradiol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No

Summary:

      The project is a two-arm prospective cohort and pharmacokinetic study comparing
      levonorgestrel and ethinyl estradiol pharmacokinetics in HIV-positive women taking
      antiretroviral regimens that include ritonavir to those in women who take regimens known not
      to interact with combined oral contraceptives. In addition, the prevalence of ovulation will
      be measured in each group. Participants will take a combined oral contraceptive containing
      levonorgestrel and ethinyl estradiol for 21 days, during which they will undergo twice-weekly
      serum progesterones. On the final day, they will complete a pharmacokinetic study. The
      investigators hypothesize that levonorgestrel levels, as measured by area-under-the-curve
      from 0 to 72 hours, will be increased in women on ritonavir, while ethinyl estradiol levels
      will be decreased and ovulation, defined by a serum progesterone of at least 3 ng/mL, will be
      unchanged.

      This study will be the first to evaluate the effects of ritonavir on the pharmacokinetics of
      a combined oral contraceptive containing the progestin levonorgestrel. In addition, no
      previous studies have rigorously assessed ovulation in women taking protease inhibitors and
      combined oral contraceptives. As a result, this study will provide new information
      correlating pharmacokinetic changes with effects on ovulation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV positive

          -  Female

          -  Age 18-45

          -  Using any of the following medication regimens: no ARV medication, entry inhibitors,
             nucleoside reverse transcriptase inhibitors (NRTIs), integrase inhibitors, and CCR5
             agonists. Acceptable NRTI combinations include zidovudine (ZDV), lamivudine (3TC),
             emtricitabine (FTC), didanosine (ddl), stavudine (d4T), abacavir (ABC), and tenofovir
             disoproxil fumarate (TDF)

          -  Ovulatory (mid-luteal progesterone >3ng/dL)

          -  Not planning to conceive during the study period

          -  Willing to abstain from grapefruit products

          -  If taking ritonavir, willing to use alternate non-hormonal contraception

          -  BMI < or = 40

          -  Able to consent in English or Spanish

          -  No change in medication regimen for at least 21 days prior to study entry and no
             planned change during the study period

          -  CD4 > or =200, and/or not considered profoundly immuncompromised by primary HIV
             provider

        Exclusion Criteria:

          -  Using on the combination of ZDV at d4T

          -  Platelets <50,000

          -  AST or ALT > twice upper limit of normal

          -  Bilirubin > twice upper limit of normal

          -  Use of other CYP3A4 inducing or inhibiting medications

          -  Pregnant or breastfeeding in last 30 days

          -  Use of DepoProvera in last 180 days

          -  Use of any other hormonal contraception in last 30 days

          -  Undiagnosed vaginal bleeding or invasive cancer of the reproductive tract

             ->50% change in tobacco use in the last month

          -  Initiation or titration of methadone therapy in the last month

          -  Uncontrolled thyroid disease

          -  Contraindication to estrogen use

          -  Inability to comply with study protocol