Depo-Medroxyprogesterone Acetate (DMPA, Depo-Provera) Use With Certain Anti-HIV Drugs in HIV-Infected Women
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Indinavir sulfate (Drug); Ritonavir (Drug); Nelfinavir mesylate (Drug); Efavirenz (Drug); Nevirapine (Drug); Medroxyprogesterone acetate (Drug)
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Official(s) and/or principal investigator(s):
Susan Cohn, Study Chair
The purpose of this study is to look at the level of depo-medroxyprogesterone acetate (DMPA
or Depo-Provera) in the blood to see if is affected by certain anti-HIV drugs (nelfinavir
[NFV], efavirenz [EFV], indinavir [IDV] in combination with ritonavir [RTV], and nevirapine
[NVP]). This study will also look at the levels of these anti-HIV drugs to see if they are
affected by DMPA.
DMPA is a hormonal birth control method that is given as an injection. It is not known if
taking DMPA together with anti-HIV drugs changes the amount of DMPA and/or the amount of
anti-HIV drugs in the blood. If higher levels of DMPA occur, side effects may increase. If
lower levels of anti-HIV drugs occur, the drugs may become less effective against HIV. This
study will look at the levels of anti-HIV drugs and DMPA in the blood when these medications
are used together.
Official title: An Open-Label, Non-Randomized Study of Pharmacokinetic Interactions Between Depo-Medroxyprogesterone Acetate (DMPA, Depo-Provera) and Selected Protease Inhibitor (PI) and Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) Therapies Among HIV-Infected Women
Study design: Treatment, Pharmacokinetics Study
DMPA, an injectable depot formulation of medroxyprogesterone (MPA), is a commonly used form
of "progestin-only" contraception. Information is limited on the specific P450 isozymes that
metabolize MPA; however, it appears that CYP3A4 is 1 pathway of hepatic clearance. Drugs
known to be inhibitors of the CYP3A4 pathway (such as protease inhibitors [PIs]) may lead to
elevated concentrations of MPA. Secondly, MPA given as DMPA injections has been shown to
induce the activity of CYP3A4 by 25 percent. It is possible that this action may result in
enhanced clearance of the substrates of CYP3A4, including PIs and nonnucleoside reverse
transcriptase inhibitors (NNRTIs), which in turn may result in reduced drug exposure and
possible ARV failure. This study is designed to address the lack of information on potential
interactions between PIs or NNRTIs and DMPA.
Patients are enrolled into 1 of 5 arms based on their current ARV regimen:
Arm A (control group): No current ARVs or receiving nucleoside reverse transcriptase
inhibitors (NRTIs) only.
Arm B: NFV (1250 mg bid or 750 mg tid) in combination with NRTIs. Arm C: EFV (600 mg qd) in
combination with NRTIs. Arm D: IDV (800 mg bid) and RTV (100 mg bid or 200 mg bid) in
combination with NRTIs.
Arm E: NVP (200 mg bid) in combination with NRTIs. Acceptable NRTIs and any fixed combination
of these medications include: zidovudine (ZDV), lamivudine, didanosine, stavudine (d4T),
zalcitabine, and abacavir; concurrent therapy using ZDV and d4T is not allowed. ARV therapy
is not provided by this study. One dose of DMPA is provided to all patients at entry (Day 0)
and an optional dose of DMPA will be available at the final visit (Week 12) for those who are
interested in continuing with DMPA outside of the protocol and who do not experience adverse
events from the first DMPA injection. Patients in Arms B, C, D, and E have intensive
pharmacokinetic sampling done at entry and at Week 4 to measure ARV levels. All patients have
blood tests at Weeks 2, 4, 6, 8, 10, and 12 to measure levels of DMPA and progesterone. In
addition, tests to monitor HIV-1 RNA levels, CD4 and CD8 counts, hematology, blood
chemistries, and liver function are performed periodically.
Minimum age: 13 Years.
Maximum age: N/A.
Patients may be eligible for this study if they:
- Are HIV-positive.
- Have plasma HIV-1 RNA (level of HIV in the blood) below 10,000 copies/ml within 30
days before study entry.
- Had their last menstrual period (LMP) less than 35 days before study entry.
- Have serum follicle-stimulating hormone below 40 MIU/ml if their LMP occurred more
than 35 days before study entry.
- Have been on the same anti-HIV drugs for at least 30 days before study entry, if
taking anti-HIV drugs. If not taking anti-HIV drugs, patients must have been told
about anti-HIV drugs within the 3 months before study entry and have chosen not to
take them now or in the future.
- Intend to continue on their anti-HIV drugs, if taking them, for at least 3 months
after study entry.
- Have a CD4 cell count above 200 cells/mm3 if taking anti-HIV drugs, or a CD4 cell
count above 350 cells/mm3 if not taking anti-HIV drugs, within 30 days before study
- Have not had menopause (change of life) and have a normal reproductive system.
- Have not had any infections or AIDS-related diseases requiring drugs within 14 days
before study entry.
- Are 13 years of age or older.
- Are female.
- Have a negative pregnancy test within 30 days before study entry.
- Agree to avoid becoming pregnant for the entire study. If sexually active, agree to
use at least 1 barrier method of birth control (male or female condom with or without
spermicide [a cream or gel that kills sperm] or diaphragm or cervical cap with
spermicide) while receiving DMPA in this study.
- Have consent of a parent or guardian if under 18 years of age.
- Weigh at least 40 kg (88 lbs) and are within a certain range of their ideal body
Patients will not be eligible for this study if they:
- Have taken anti-HIV drugs within 30 days before study entry but have chosen not to
- Are taking only 1 NRTI.
- Are taking anti-HIV drugs other than those listed in the treatment groups, including
tenofovir, amprenavir, and lopinavir/ritonavir, or have taken tenofovir, amprenavir,
or lopinavir/ritonavir within 30 days before study entry.
- Have taken ZDV and d4T together within 30 days before study entry.
- Are not able to take the anti-HIV drugs properly while on the study, in the opinion of
- Are allergic to DMPA, MPA, or any of the other ingredients in DMPA.
- Have received DMPA within 180 days before study entry.
- Have received other hormones (Provera, oral contraceptives, hormonal replacement
therapy, or anabolic drugs [e. g., nandrolone decanoate, megestrol acetate]) within 30
days before study entry.
- Are taking any of the following: amiodarone, astemizole, bepridil, buspirone,
carbamazepine, cimetidine, cisapride, clarithromycin, cyclosporine, dihydroergotamine,
diltiazem, ergotamine, erythromycin, flecainide, glucocorticoids, grapefruit juice,
St. John's wort, itraconazole, ketoconazole, lovastatin, midazolam, nefazodone,
phenobarbital, phenytoin, pimozide, pioglitazone, propafenone, propofol, quinidine,
rifabutin, rifampin, rosiglitazone, simvastatin, tacrolimus, terfenadine, ticlopidine,
triazolam, or verapamil.
- Have taken any of the following drugs within 30 days before study entry: amiodarone,
astemizole, bepridil, buspirone, carbamazepine, cisapride, clarithromycin,
cyclosporine, dihydroergotamine, ergotamine, erythromycin, flecainide,
glucocorticoids, St. John's wort, itraconazole, ketoconazole, lovastatin, midazolam,
nefazodone, phenobarbital, phenytoin, pimozide, pioglitazone, propafenone, propofol,
quinidine, rifabutin, rifampin, rosiglitazone, simvastatin, tacrolimus, terfenadine,
ticlopidine, or triazolam.
- Have started, stopped, or changed doses, within 30 days before study entry, of certain
drugs including: benzodiazepines, except midazolam and triazolam; bupropion; calcium
channel blockers, except diltiazem and verapamil; fluconazole; lipid-lowering drugs
except pravastatin (i. e., atorvastatin, cerivastatin, and fluvastatin, but not
lovastatin and simvastatin); isoniazid; mexiletine; zaleplon; and zolpidem. The
patient can, however, remain on stable doses of these drugs during the study.
- Are receiving methadone maintenance treatment for less than 60 days before study
- Are breast-feeding.
- Have had a baby within 30 days before study entry.
- Have had their uterus or both ovaries removed.
- Abuse drugs or alcohol.
- Cannot stop drinking alcohol 1 day before and during the testing at entry and at Week
- Have had a change in smoking habits within 6 weeks before study entry. Patients may
have either stopped or started smoking more than 6 weeks before study entry.
- Have cancer of the reproductive system, vaginal bleeding of unknown cause, thyroid
problems, liver tumors, or serious eye problems at any time before study entry.
- Are taking investigational drugs without approval of the protocol chair.
Locations and Contacts
San Juan City Hosp, San Juan 009367344, Puerto Rico
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Children's Hosp of Denver, Denver, Colorado 802181088, United States
Univ of Miami (Pediatric), Miami, Florida 33161, United States
Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States
Univ of Illinois College of Medicine / Pediatrics, Chicago, Illinois 60612, United States
Mt Sinai Hosp Med Ctr / Dept of Pediatrics, Chicago, Illinois 60608, United States
Chicago Childrens Memorial Hosp (Pediatric), Chicago, Illinois 60614-3394, United States
The Univ of Chicago Childrens Hosp, Chicago, Illinois 60637, United States
Indiana Univ Hosp, Indianapolis, Indiana 46202-5250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Wishard Hosp, Indianapolis, Indiana 46202, United States
Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States
Univ of Maryland, Institute of Human Virology, Baltimore, Maryland 21201, United States
Boston Med Ctr (Pediatric), Boston, Massachusetts 02118, United States
Children's Hosp of Michigan, Detroit, Michigan 48201, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse, New York 13210, United States
Beth Israel Med Ctr, New York, New York 10003, United States
Columbia Presbyterian Med Ctr, New York, New York 10032, United States
St Mary's Hosp (Univ of Rochester/Infectious Diseases), Rochester, New York 14642, United States
Community Health Network, Inc, Rochester, New York 14642-0001, United States
Univ of North Carolina, Chapel Hill, North Carolina 27514, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
MetroHealth Med Ctr, Cleveland, Ohio 44109-1998, United States
Case Western Reserve Univ, Cleveland, Ohio 44106-5083, United States
Univ of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States
Univ of Washington, Seattle, Washington 98104, United States
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Last updated: January 31, 2008