Fortovase (Saquinavir) Given With Low-Dose Ritonavir, Zidovudine, and Lamivudine to HIV-Positive Pregnant Women During and After Pregnancy and to Their Newborns

Condition(s) targeted: HIV Infections; Pregnancy

Intervention: Ritonavir (Drug); Saquinavir (Drug); Lamivudine (Drug); Zidovudine (Drug)

Phase: Phase 1

Status: Completed

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

Official(s) and/or principal investigator(s):
Carmen Zorrilla, Study Chair
Arlene Bardeguez, Study Chair
Jane Pitt, Study Chair
Russell Van Dyke, Study Chair

The purpose of this study is to see if it is safe to give saquinavir-SGC (SQV) combined with low-dose ritonavir (RTV) plus zidovudine (ZDV) and lamivudine (3TC) to HIV-positive pregnant women and to see if it is safe to give 3TC and ZDV to their newborns. Another purpose is to see what levels of SQV, low-dose RTV, ZDV, and 3TC are found in mothers and what levels of ZDV and 3TC are seen in newborns. Another purpose of this study is to see whether SQV passes from mother to newborn and if it passes at a level that is safe for the newborn.

Although ZDV has been able to reduce the rate of transmission of HIV from mother to child, it may be possible to reduce it further by using a combination of anti-HIV drugs. This study adds SQV (a protease inhibitor [PI]) with RTV (another PI) and 3TC (a reverse transcriptase inhibitor) to the mother's ZDV regimen.

Official title: A Phase I Trial of the Safety and Pharmacokinetics of Fortovase (Saquinavir-SGC) Co-Administered With Low Dose (Ritonavir) RTV, ZDV and 3TC in HIV Seropositive Pregnant Women During Gestation and Postpartum, and in Their Infant's Post-Maternal Dosing

Study design: Treatment, Pharmacokinetics Study

Detailed description: Although administration of ZDV to mother-infant pairs has dramatically reduced perinatal HIV infection, the goal is to reduce it further to less than 2%. In order to achieve this, combination strategies need to be developed for 2 purposes: 1) to reduce the perinatal transmission rate to goal levels; and 2) to provide other combination therapies for HIV-infected mothers whose virus has become resistant to ZDV, who have a very high viral load, or who have previously transmitted HIV while on ZDV. This study adds 3TC (another reverse transcriptase inhibitor) and SQV (a protease inhibitor [PI]) [AS PER AMENDMENT 08/15/00: with low-dose RTV (another PI)] to the mother's ZDV regimen.

During the antepartum period, mothers receive SQV with [AS PER AMENDMENT 08/15/00: low-dose RTV plus] ZDV and 3TC. At onset of active labor, mothers receive loading doses of each of the study drugs, then receive study drugs for 12 weeks postpartum on the same schedule as during the antenatal period. Within 12 hours of delivery, infants begin receiving 3TC and ZDV and continue until 6 weeks of age. Mothers are followed until 12 weeks postpartum and babies are followed until 6 months of age. [AS PER AMENDMENT 02/09/99: For maternal dosing, 1 Combivir tablet (containing 3TC and ZDV) may be administered in place of the individual agents 3TC and ZDV. Patients who prematurely discontinue study treatment should continue to be followed for the duration of the study.]

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria

Patients may be eligible for this study if they:

- Are HIV-positive.

- Are 14 to 32 weeks pregnant.

- Are at least 13 years old (need consent of parent or guardian if under 18).

Exclusion Criteria

Patients may not be eligible for this study if they:

- Cannot take ZDV, 3TC, or higher doses of RTV. Women who are able to tolerate low doses

of RTV may be eligible.

- Are pregnant with more than 1 baby. (This study has been changed so that a patient

pregnant with more than 1 baby is not eligible.)

- Have pregnancy complications or have medical problems that put pregnancy at risk.

- Have an active opportunistic (HIV-related) infection and/or serious bacterial

infection at study entry.

- Have chronic diarrhea.

- Abuse alcohol or drugs.

- Do not have access to a participating clinic or are not willing to be followed at the

same clinic for the duration of the study.

- Have received certain antiretroviral (anti-HIV) drugs or are taking certain

medications. (This study has been changed to increase enrollment. The eligibility criterion in earlier versions was more restrictive, and has been changed to include women receiving SQV [with or without RTV], 3TC, and ZDV for longer than 3 weeks if their pre-entry viral load is 400 copies/ml or less OR if they have a significant reduction in viral load within 90 days of the pre-entry visit.)

- Plan to breast-feed.

Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico

Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States

Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States

Howard Univ Hosp, Washington, District of Columbia 20060, United States

Univ of Miami (Pediatric), Miami, Florida 33161, United States

Univ of Miami / Jackson Memorial Hosp, Miami, Florida 33136, United States

Univ of Illinois College of Medicine / Pediatrics, Chicago, Illinois 60612, United States

Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States

Univ Hosp, New Orleans, Louisiana 70112, United States

Children's Hosp of Michigan, Detroit, Michigan 48201, United States

Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States

Columbia Presbyterian Med Ctr, New York, New York 10032, United States

Duke Univ Med Ctr, Durham, North Carolina 277103499, United States

Med Univ of South Carolina, Charleston, South Carolina 294253312, United States

Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States

Click here for more information about Zidovudine

Click here for more information about Lamivudine

Click here for more information about Saquinavir

Click here for more information about Ritonavir

Haga clic aquí para ver información sobre este ensayo clínico en español.

Related publications:

Acosta EP, Zorrilla C, Van Dyke R, Bardeguez A, Smith E, Hughes M, Huang S, Pitt J, Watts H, Mofenson L. Pharmacokinetics of saquinavir-SGC in HIV-infected pregnant women. HIV Clin Trials. 2001 Nov-Dec;2(6):460-5.

Starting date: September 1997
Last updated: June 23, 2005