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Depo-Medroxyprogesterone Acetate (DMPA, Depo-Provera) Use With Certain Anti-HIV Drugs in HIV-Infected Women

Not Applicable
Completed
Conditions
HIV Infections
Registration Number
NCT00016601
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
76
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (32)

Univ of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Univ of Southern California / LA County USC Med Ctr

🇺🇸

Los Angeles, California, United States

Los Angeles County - USC Med Ctr

🇺🇸

Los Angeles, California, United States

Children's Hosp of Denver

🇺🇸

Denver, Colorado, United States

Univ of Florida Health Science Ctr / Pediatrics

🇺🇸

Jacksonville, Florida, United States

Univ of Miami (Pediatric)

🇺🇸

Miami, Florida, United States

Mt Sinai Hosp Med Ctr / Dept of Pediatrics

🇺🇸

Chicago, Illinois, United States

Univ of Illinois College of Medicine / Pediatrics

🇺🇸

Chicago, Illinois, United States

Chicago Childrens Memorial Hosp (Pediatric)

🇺🇸

Chicago, Illinois, United States

The Univ of Chicago Childrens Hosp

🇺🇸

Chicago, Illinois, United States

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Univ of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States

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