PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB
Condition: HIV-1 Infection; Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study was done to evaluate the effect of HIV and TB treatment on a commonly used birth
      control method. It enrolled women who were infected with HIV and TB and were taking efavirenz
      (EFV; Sustiva®; an anti-HIV medication), rifampicin (RIF; an anti-TB medication), and
      isoniazid (INH; an anti-TB medication). The purpose of this study was to find out the best
      frequency to give depot medroxyprogesterone acetate (DMPA; a hormonal birth control method
      that is given as a shot every 3 months) in these women. This study also tried to find out if
      a 150 mg injection of DMPA was effective in preventing ovulation, the process by which the
      ovaries (the ovaries are part of the female reproductive system) release an egg for
      fertilization, for 12 weeks in women who are taking EFV and RIF. Another purpose of this
      study was to find out if it is safe to take RIF, EFV and DMPA at the same time.
    

Detailed description: 
      Globally, women comprise 52% of all people living with human immunodeficiency virus (HIV).
      Decisions about contraception in a population of women infected with both tuberculosis (TB)
      and HIV are of paramount importance. In the setting of the treatment of active TB, preventing
      pregnancy becomes even more important because it allows women to attain a level of health
      that will support healthy future pregnancies. Treatment options for TB may be limited in
      pregnancy because of concerns about teratogenicity. Millions of women around the world use
      depot medroxyprogesterone acetate (DMPA, trade name Depo-Provera) for prevention of
      pregnancy. DMPA is an intermediate-acting progesterone-only injectable contraceptive with a
      high efficacy rate. Unfortunately, DMPA's safety and effectiveness among women co-infected
      with TB and HIV is unknown since the interactions of TB treatment, combination ART (cART),
      and DMPA have not been well studied. The results of this study are likely to be applicable to
      women receiving RIF-containing TB treatment who are not being treated concurrently with EFV
      as well, given that addition of EFV to RIF is unlikely to increase induction of metabolizing
      enzymes significantly beyond the induction achieved with RIF alone.

      The study population included premenopausal women, 18 to 46 years of age, who were
      co-infected with HIV and TB. To be eligible to enroll in the study, participants must have
      been on EFV 600 mg once daily plus two or more nucleoside reverse transcriptase inhibitors
      (NRTIs) for at least 28 days prior to study entry with no plans to change therapy for the 12
      weeks of the study. Women must have been on the continuation phase of active TB treatment
      (with a minimum of 12 weeks remaining) taking RIF 8-12 mg/kg orally and INH 4-6 mg/kg orally
      on a 5-day or more per week schedule (or as directed by national guidelines for TB
      treatment). At study entry/week 0, DMPA 150 mg was administered intramuscularly as a single
      dose.

      Study duration was 12 weeks. Visits occurred at weeks 0, 2, 4, 6, 8, 10, and 12. The key
      evaluations included physical examination, clinical assessments, hematology, chemistry, HIV
      RNA, pregnancy testing, plasma progesterone levels, and plasma DMPA concentration levels.

      The sample size was 46 participants, of which 42 had to be evaluable. Participants who missed
      two successive visits prior to week 8 and those who did not complete the week 10 and week 12
      clinic visits with available DMPA concentrations and progesterone levels were not evaluable
      and replaced in the sample size. The final number of participants enrolled was 62
      participants, with only 42 evaluable.
    

Intervention name(s): Depot medroxyprogesterone acetate
Intervention type(s): Drug
Intervention description(s): Depot medroxyprogesterone acetate intramuscular injection
Other intervention name(s): DMPA
Intervention MeSH terms: Medroxyprogesterone Acetate; Medroxyprogesterone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment