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A Study to Evaluate the Effects of Different Methods of Birth Control on the Drug Actions of Zidovudine (an Anti-HIV Drug) in HIV-Positive Women and to Compare Zidovudine Metabolism in Men and Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00000897
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : March 2, 2011
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

The purpose of this study is to look at the effects of different methods of birth control (oral and injectable) on how the body absorbs, makes available, and removes zidovudine (ZDV). This study will also evaluate the differences in men and women in how the body absorbs, makes available, and removes ZDV.

Past research has shown that the effectiveness of ZDV as an anti-HIV drug might be decreased in individuals who use certain methods of birth control. ZDV may also have different effects in men compared to women.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Zidovudine Not Applicable

Detailed Description:

Oral contraceptives have been shown to substantially enhance the glucuronidation of several compounds. One study reported enhanced glucuronidation of oxazepam, a compound that is conjugated via the same UDP-glucuronyl transferase isozyme responsible for ADV glucuronidation, suggesting that ZDV metabolism may be altered by concomitant oral contraceptive use. This potential enhancement of ZDV metabolism by oral contraceptives is expected to result in decreased plasma levels of the parent compound which may lead to diminished clinical efficacy in women using these drugs. It remains unclear whether the progesterone and/or estrogen component of oral contraceptives results in the observed glucuronidation changes.

This open-label, pharmacokinetic trial is conducted in 2 steps. [AS PER AMENDMENT 6/12/01: The Depo-Provera IM group in Step 2 is filled. Female patients who choose to participate in Step 2 may enroll only in the Ortho-Novum 1/35 PO group.] [AS PER AMENDMENT 11/13/00: Female patients may choose to participate in Step 1 alone or both Steps 1 and 2.] Male patients may participate in Step 1 only as the control arm of the study. In Step 1, patients are stratified by sex; in Step 2, female patients are stratified by their choice of contraception (i.e., oral norethindrone/ethinyl estradiol [Ortho-Novum 1/35] or injectable medroxyprogesterone acetate [Depo-Provera]).

Step 1 (males and females): At entry, all patients are randomized to receive ZDV either orally or orally and intravenously (IV) on Days 7 and 8. Female patients begin the study (Day 0) between days 10-18 after the first day of their last menstrual period (LMP) (Cycle 1). At time of enrollment, female patients [AS PER AMENDMENT 11/13/00: who plan to participate in Step 2] choose the form of birth control instituted in Step 2: Depo-Provera or Ortho-Novum 1/35. Male patients may enter Step 1 at any time. Patients continue taking their other pre-study antiretroviral drugs during Step 1. [AS PER AMENDMENT 6/3/99: Patients taking nelfinavir may participate only in the Depo-Provera arm.] Days 0-6: All patients receive oral ZDV. Day 7: Patients are randomized to receive:

Arm 1 (females): oral ZDV for a total of 3 doses. Arm 2 (females): ZDV IV, then ZDV orally for a total of 2 oral doses. Arm 3 (males): control arm. Half of the male patients receive ZDV as in Arm 1 and the other male patients receive ZDV as in Arm 2.

Day 8: Patients on all 3 arms receive the alternate form of ZDV to that received on Day 7. Day 9: Female patients resume their pre-study method of administration of ZDV. Male patients conclude their participation in the study on Day 8.

Step 2 (females [AS PER AMENDMENT 11/13/00: opting to participate in Step 2]): At the onset of their second menstrual period (Cycle 2) since starting study, female patients start their choice of Ortho-Novum 1/35 or intramuscularly administered Depo-Provera [AS PER AMENDMENT 6/12/01: Enrollment for Depo-Provera is closed]. Contraceptive therapy continues throughout Step 2. Step 2 Days 0-6: Between days 7-11 [AS PER AMENDMENT 6/3/99: Between days 7-18] of the third menstrual cycle (Cycle 3) since starting study, female patients continue their pre-study antiretroviral therapy (as done in Step 1) and begin another course of ZDV standard therapy 3 times daily. Days 7-8: Patients receive the original method of administration of ZDV (as randomized at study entry). Female patients return for a final safety visit within 1 week of completing study Day 8 of Step 2.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 42 participants
Primary Purpose: Treatment
Official Title: The Effect of Oral and Injectable Contraceptives (Norethindrone/Ethinyl Estradiol, Medroxyprogesterone Acetate) and Gender on Plasma and Intracellular Zidovudine Pharmacokinetics
Actual Primary Completion Date : October 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Zidovudine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

Men and women may be eligible for this study if they:

  • Are HIV positive.

Women may be eligible for this study if they:

  • Have regular periods and a normal gynecological exam, (including a Pap smear and mammogram).
  • Enter the study between Days 10 and 18 of the first day of their last period.
  • Are willing to use either the Pill or Depo-Provera as birth control.
  • Have a negative pregnancy test within 14 days prior to study.

Exclusion Criteria

Men and women will not be eligible for this study if they:

  • Cannot take ZDV for any reason.
  • Have cancer.
  • Are taking stavudine.

Women will not be eligible for this study if they:

  • Cannot take the Pill or Depo-Provera.
  • Are pregnant or nursing.
  • Are receiving nelfinavir and want to enroll in Step 2.
  • Have a history of chronic high blood pressure, thrombophlebitis, and/or pulmonary emboli if participating in Step 2 of the study.

(This study has been changed so that women with certain criteria are excluded from participating in Step 2.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00000897

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United States, California
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, Florida
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, United States, 32209
United States, New York
Children's Hosp at Albany Med Ctr
Albany, New York, United States, 12208
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Study Chair: Francesca Aweeka
Layout table for additonal information Identifier: NCT00000897    
Other Study ID Numbers: ACTG 317
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: March 2, 2011
Last Verified: March 2011
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Interactions
Sex Factors
Reverse Transcriptase Inhibitors
Contraceptives, Oral
Progestational Hormones, Synthetic
Anti-HIV Agents
Viral Load
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents