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 people who are not pregnant. This study will use pharmacokinetic (PK) sampling (a way to find out how drugs act in the body) to determine what doses of which anti-HIV medications are best for HIV infected pregnant women and their infants.

Condition	Treatment or Intervention
HIV Infections	Drug: Abacavir sulfate  Drug: Atazanavir  Drug: Didanosine, enteric coated  Drug: Emtricitabine  Drug: Fosamprenavir  Drug: Lopinavir/Ritonavir  Drug: Ritonavir  Drug: Tenofovir disoproxil fumarate

Further Study Details: 

Expected Total Enrollment:  125

Pregnant women experience unique physiological changes that may result in clinically significant alterations in drug pharmacokinetics. Unfortunately, there have been few clinical trials to study the pharmacokinetics of antiretroviral drugs 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 to identify those that are most effective in preventing perinatal HIV transmission and in maintaining the health of both mother and fetus.

Women must be stable on their antiretroviral drug for at least two weeks prior to PK sampling and planning to continue on their current regimen until at least six weeks postpartum. The timing of antiretroviral dosing for the three days prior to and the day of PK sampling must be the same, and must be the same for the PK samplings during pregnancy and postpartum. Intensive PK sampling is performed at study visits during the second or third trimester of pregnancy and again between either 2 and 3 weeks or 6 and 12 weeks postpartum. The timing of antepartum and postpartum PK samplings will vary by drug. On the day of PK sampling, study visits are scheduled to start in the morning, will last 6 to 24 hours, and will coincide with the end of the previous dosing cycle. At the end of the dosing cycle, the morning dose of the antiretroviral drug(s) is given in the clinic after the predose PK sample is drawn. Serial blood collection is performed with an intravenous catheter that is placed in a vein in each patient's arm. Patients having 6- or 12-hour sampling should remain in the clinic until the completion of PK sampling. Patients having 24-hour sampling may leave the clinic following the 12-hour timepoint and return for the 24-hour timepoint.

A urine sample is also collected at each visit and a brief medical interview is performed. An intrapartum PK sample is obtained from the patient and from the detached umbilical cord. The patient and clinical caregiver may decide to modify dosing. If they do so, repeat PK sampling is offered at the new dose. Additionally, women who are on regimens containing ritonavir will undergo a brief medical interview, physical and obstetric exams, and blood collection at entry, every 4 weeks from entry to the 30th week of pregnancy, every 2 weeks from the 30th week of pregnancy to delivery, and every 4 weeks postpartum until the end of the study. They will also undergo an electrocardiogram 4 weeks after they enter the study.

Genders Eligible for Study:  Female

Criteria

Inclusion Criteria

• HIV infected
• At least 20 weeks pregnant
• Enrolled in PACTG P1025
• Must begin one of the study drugs or drug combinations by 34 6/7th week of pregnancy, and must be on the drug or drug combination for at least 2 weeks prior to PK sampling
• Note: 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.

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

Shiara Ortiz-Pujols      301-628-3559 

Alabama
      University of Alabama at Birmingham (Pediatric), Birmingham,  Alabama,  35233,  United States; Recruiting
California
      UCSD Mother, Child, Adolescent HIV Program, San Diego,  California,  92103,  United States; Recruiting
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States; Recruiting
      UCSD Mother, Child & Adolescent HIV Program, San Diego,  California,  92103,  United States; Recruiting
      UCLA Med Ctr (Pediatrics), Los Angeles,  California,  90090-1752,  United States; Recruiting
      UCSF, Moffitt Hosp (Pediatric), San Francisco,  California,  94143-0105,  United States; Recruiting
      Los Angeles County Medical Center/USC, Los Angeles,  California,  90033,  United States; Recruiting
Colorado
      Childrens Hospital (U. Colorado, Denver), Denver,  Colorado,  80218-1088,  United States; Recruiting
Connecticut
      Yale University School of Medicine, New Haven,  Connecticut,  06504,  United States; Recruiting
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33136,  United States; Recruiting
      Jackson Memorial Hosp, Miami,  Florida,  33136,  United States; Recruiting
Georgia
      Medical College of Georgia, Augusta,  Georgia,  30912,  United States; Recruiting
Illinois
      The University of Chicago Childrens Hospital, Chicago,  Illinois,  60637,  United States; Recruiting
      Chicago Childrens Memorial Hospital (Pediatric), Chicago,  Illinois,  60614,  United States; Recruiting
      University of Illinois, Chicago,  Illinois,  60612-7234,  United States; Recruiting
Louisiana
      University Hospital, New Orleans,  Louisiana,  70112-2699,  United States; Recruiting
Maryland
      Shiara Ortiz-Pujols, Silver Spring,  Maryland,  20910,  United States; Recruiting
      University of Maryland (Pediatrics), Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Boston Medical Center (Pediatric), Boston,  Massachusetts,  02118,  United States; Recruiting
      Brigham and Women's Hospital, Boston,  Massachusetts,  02478,  United States; Recruiting
      University of Massachusetts Medical School, Worcester,  Massachusetts,  01655-0001,  United States; Recruiting
      Baystate Medical Center, Springfield, Springfield,  Massachusetts,  01199,  United States; Recruiting
Missouri
      St. Louis Children's Hospital, St. Louis,  Missouri,  63110,  United States; Recruiting
New Jersey
      Univ of Med & Dentistry of NJ/Univ Hosp, Newark,  New Jersey,  07103,  United States; Recruiting
New York
      The Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States; Recruiting
      Jacobi Medical Center, Bronx,  New York,  10461,  United States; Recruiting
      State University of New York at Stony Brook, Stony Brook,  New York,  11794-8111,  United States; Recruiting
      Bronx Lebanon Hospital Center, Bronx,  New York,  10457,  United States; Recruiting
North Carolina
      Duke University (Pediatric), Durham,  North Carolina,  27705,  United States; Recruiting
Pennsylvania
      Hahnemann University Hospital, Philadelphia,  Pennsylvania,  19102-1192,  United States; Recruiting
Tennessee
      St. Jude Childrens Research Hospital, Memphis, Memphis,  Tennessee,  38105-2794,  United States; Recruiting
      Vanderbilt University Medical Center, Nashville,  Tennessee,  37232-2581,  United States; Recruiting
Washington
      Children's Hospital and Regional Medical Center, Seattle,  Washington,  98105-0371,  United States; Recruiting
      Northwest Family Center/Harborview Medical Center, Seattle,  Washington,  98105-0371,  United States; Recruiting
      University of Washington Medical Center, Seattle,  Washington,  98105-0371,  United States; Recruiting
Puerto Rico
      San Juan City Hosp, San Juan,  Puerto Rico; Recruiting
      Univ of Puerto Rico, U. Children's Hosp AIDS, San Juan,  00936-5067,  Puerto Rico; Recruiting

Study chairs or principal investigators

Mark Mirochnick, MD,  Study Chair,  Boston Medical Center   

Study ID Numbers:  PACTG P1026S; PACTG P1025
Record last reviewed:  January 2005
Last Updated:  April 7, 2005
Record first received:  July 26, 2002
ClinicalTrials.gov Identifier:  NCT00042289
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08