The purpose of this study is to see if giving nelfinavir (NFV) plus zidovudine (ZDV) plus lamivudine (3TC) to HIV-positive pregnant women and their babies is safe. This study will also look at how long these drugs stay in the blood. ZDV has been given to mothers in the past to reduce the chances of passing HIV on to their babies. However, better treatments are needed to further reduce these chances and to better suit the treatment needs of mothers and their children. Taking a combination of anti-HIV drugs during pregnancy may be an answer.

Condition	Treatment or Intervention	Phase
HIV Infections Pregnancy	Drug: Nelfinavir mesylate  Drug: Lamivudine  Drug: Zidovudine	Phase I

Further Study Details: 

Expected Total Enrollment:  24

Despite the dramatic reduction of perinatal HIV transmission by the administration of ZDV to mother and infant, new and more potent strategies are needed to further reduce perinatal transmission and better suit the diverse treatment needs of these patients. Initiation of triple antiretroviral combinations during gestation, particularly combinations that include drugs that cross the placenta such as 3TC, may be the most effective in reducing maternal virus load to its lowest levels prior to delivery.

Women receive nelfinavir plus 3TC plus ZDV antepartum (Study Day 0 until onset of active labor) through postpartum (after cord clamped to 12 weeks). [AS PER AMENDMENT 10/28/97: If patient presents in active labor with less than 1 hour to delivery time, the institutional protocol for ZDV infusion during labor should be followed.] [AS PER AMENDMENT 1/26/99: For maternal dosing, one Combivir tablet bid can be substituted for the individual formulation of 3TC and ZDV. For mothers who receive Combivir during the antepartum period, Combivir is held during labor and delivery, and the separate formulations of ZDV and 3TC are used. Patients who prematurely discontinue study treatment should continue to be followed on study for the duration of the study.] Full pharmacokinetic sampling is performed 10 to 15 days after start of therapy [AS PER AMENDMENT 2/7/00: 10 to 15 days after study entry for women currently taking nelfinavir] and again 5 to 6 weeks after delivery. A maternal blood sample and cord blood sample is collected at birth for analysis of nelfinavir concentrations. Maternal HIV RNA in plasma is monitored throughout the study. Cervicovaginal secretions are collected at entry, late gestation, and postpartum to assess the presence of HIV. A single pharmacokinetics sample is collected with each cervicovaginal secretion. Serial CD4/CD8 activation markers are measured in women during gestation and postpartum. Infants receive nelfinavir plus 3TC plus ZDV beginning approximately 12 hours following birth and continuing for 6 weeks. After birth, several blood samples are collected from the infant for determination of washout kinetics of nelfinavir. Full pharmacokinetics sampling is performed 5 to 8 days post birth and 5 to 6 weeks following multiple doses. Pharmacokinetic samples are analyzed on the first six mother-infant pairs and dosing may be adjusted accordingly for the next cohort. Agouron has agreed to make nelfinavir available to all interested study participants for a period of 6 months after the study via the patient assistance program.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Female

Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

• Are at least 13 years old (need consent of parent or guardian if under 18).
• Are HIV-positive.
• Are in the 2nd or 3rd trimester (14 to 34 weeks pregnant) and are pregnant with one or two children.
• Have a normal ultrasound exam.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Cannot take ZDV or 3TC.
• Have an active opportunistic (HIV-associated) or bacterial infection, or a severe medical condition.
• Have severe diarrhea.
• Are at risk for premature birth or pregnancy complications.
• Have a family history of phenylketonuria (PKU).
• Plan to breast-feed.
• Abuse alcohol or drugs.
• Cannot visit the same clinic for the duration of the study.
• Have taken certain anti-HIV drugs.

California
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States
      Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles,  California,  905022004,  United States
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
Florida
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
Illinois
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Univ of Chicago Children's Hosp, Chicago,  Illinois,  606371470,  United States
      Mt Sinai Hosp Med Ctr / Dept of Pediatrics, Chicago,  Illinois,  60608,  United States
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States
      Univ Hosp, New Orleans,  Louisiana,  70112,  United States
Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States
      Johns Hopkins Hosp - Pediatric, Baltimore,  Maryland,  212874933,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
      Boston City Hosp / Pediatrics, Boston,  Massachusetts,  02118,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
      Univ of Massachusetts Med School, Worcester,  Massachusetts,  016550001,  United States
Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
New York
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States
North Carolina
      Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Pennsylvania
      Temple Univ School of Medicine, Philadelphia,  Pennsylvania,  191341095,  United States
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico

Study chairs or principal investigators

Yvonne Bryson,  Study Chair
Mark Mirochnick,  Study Chair
Alice Stek,  Study Chair

Study ID Numbers:  ACTG 353; PACTG 353
Record last reviewed:  September 2004
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000887
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08