Pharmacokinetic Study of Anti-HIV Drugs During Pregnancy - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00042289

Purpose

The purpose of this study is to determine what doses of anti-HIV medications are appropriate for pregnant women.

Anti-HIV medication taken during pregnancy may control a woman's viral load and reduce the chance that the baby will become infected with HIV. Pregnant women may require different doses of anti-HIV drugs than women who are not pregnant. This study will use pharmacokinetic (PK) sampling to determine what doses of anti-HIV medications are best for HIV-infected pregnant women and their infants.

Condition	Intervention
HIV Infections	Procedure: Pharmacokinetic sampling

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Pharmacokinetic Properties of Antiretroviral Drugs During Pregnancy

Resource links provided by NLM:

MedlinePlus related topics: AIDS AIDS Medicines AIDS and Pregnancy

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Area under the curve (AUC) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Ratio of cord blood concentration to maternal blood concentration [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Ratio of 6-beta-hydroxycortisol to cortisol [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Ratio of unbound/total drug concentrations for atazanavir, fosamprenavir, indinavir, lopinavir, efavirenz, nelfinavir, tipranavir, and darunavir [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	275
Study Start Date:	March 2003
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will be evaluated in order to determine the most effective dosing regimen in preventing perinatal HIV transmission.	Procedure: Pharmacokinetic sampling PK sampling to determine most effective dosing regimen

Detailed Description:

Pregnant women experience unique physiological changes that may result in clinically significant alterations in drug PKs. Unfortunately, there have been few clinical trials to study the PK of antiretroviral (ARV) medications in pregnant women. The development of appropriate dosing regimens for the HIV-infected pregnant woman is critical to the health of both mother and fetus. Overdosing may lead to maternal adverse events and increased risk of fetal toxicity, while underdosing may lead to inadequate virologic control, increased risk of developing drug resistance mutations, and a higher rate of perinatal HIV transmission. This study will develop and evaluate dosing regimens that are most effective in preventing perinatal HIV transmission and in maintaining the health of both mother and fetus.

Participants will be enrolled in this study starting from their twentieth week of pregnancy and for 12 weeks after delivery. Participants will not receive ARV medications through this study. Medical history, a physical exam, and blood and urine collection will occur during all study visits. Intensive PK sampling will be performed at study visits during the second and third trimester of pregnancy and between 2 and 3 weeks and 6 and 12 weeks postpartum. The timing of antepartum and postpartum PK samplings will vary by drug. Blood collection from the mother and the detached umbilical cord will occur during delivery. Additional study visits may occur depending on the ARV drug regimen prescribed.

Eligibility

Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-infected
At least 20 weeks pregnant. If a woman has completed P1026s and becomes pregnant again, she may be eligible to re-enroll in P1026s only if she is receiving a different drug or drug combination than that studied during the first enrollment in P1026s.
Must begin one of the study drugs or drug combinations by 34 6/7th week of pregnancy, and must be on the anti-HIV drugs for at least 2 weeks prior to PK sampling. More information on this criterion can be found in the protocol.

Exclusion Criteria:

Certain medications known to interfere with absorption, metabolism, or clearance of the anti-HIV drug(s) being evaluated
Pregnant with more than one baby
Signs of toxicity that, in the opinion of the site investigator, would be likely to require a change in medication during the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00042289

Contacts

Contact: Emily F. Demske

301-628-3322

Show 47 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Study Chair:

Mark Mirochnick, MD

Boston Medical Center

More Information

Additional Information:

Click here for more information about drug regimens and pregnancy This link exits the ClinicalTrials.gov site

Click here for more information about drug safety and pregnancy This link exits the ClinicalTrials.gov site

Click here for more information on after birth care for HIV positive women and their babies This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español This link exits the ClinicalTrials.gov site

Publications:

Best BM, Mirochnick M, Capparelli EV, Stek A, Burchett SK, Holland DT, Read JS, Smith E, Hu C, Spector SA, Connor JD; the PACTG P1026s Study Team. Impact of pregnancy on abacavir pharmacokinetics. AIDS. 2006 Feb 28;20(4):553-560.

Stek AM, Mirochnick M, Capparelli E, Best BM, Hu C, Burchett SK, Elgie C, Holland DT, Smith E, Tuomala R, Cotter A, Read JS; for the PACTG 1026s study team. Reduced lopinavir exposure during pregnancy. AIDS. 2006 Oct 3;20(15):1931-1939.

Loutfy MR, Walmsley SL. Treatment of HIV infection in pregnant women: antiretroviral management options. Drugs. 2004;64(5):471-88.

Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet. 2004;43(15):1071-87. Review.

Rakhmanina NY, van den Anker JN, Soldin SJ. Safety and pharmacokinetics of antiretroviral therapy during pregnancy. Ther Drug Monit. 2004 Apr;26(2):110-5. Review.

Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. Review.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	IMPAACT P1026s, IMPAACT P1025
Study First Received:	July 26, 2002
Last Updated:	June 2, 2009
ClinicalTrials.gov Identifier:	NCT00042289 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Pregnancy
Pharmacokinetics
Treatment Experienced

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on September 11, 2009