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

NCT ID: NCT00000920

Last Updated: 2021-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2003-04-30

Brief Summary

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.

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.]

Conditions

HIV Infections; Pregnancy

Keywords

Pregnancy; Drug Therapy, Combination; Zidovudine; Pregnancy Complications; Ritonavir; Lamivudine; Saquinavir; Anti-HIV Agents

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Ritonavir

Intervention Type: DRUG

Saquinavir

Intervention Type: DRUG

Lamivudine

Intervention Type: DRUG

Zidovudine

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carmen Zorrilla

Role: STUDY_CHAIR

Arlene Bardeguez

Role: STUDY_CHAIR

Jane Pitt

Role: STUDY_CHAIR

Russell Van Dyke

Role: STUDY_CHAIR

Locations

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Howard Univ Hosp

Washington D.C., District of Columbia, United States

Univ of Miami / Jackson Memorial Hosp

Miami, Florida, United States

Univ of Miami (Pediatric)

Miami, Florida, United States

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, United States

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Univ Hosp

New Orleans, Louisiana, United States

Children's Hosp of Michigan

Detroit, Michigan, United States

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Columbia Presbyterian Med Ctr

New York, New York, United States

Duke Univ Med Ctr

Durham, North Carolina, United States

Med Univ of South Carolina

Charleston, South Carolina, United States

Children's Hospital & Medical Center / Seattle ACTU

Seattle, Washington, United States

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

Acosta EP, Zorrilla C, Van Dyke R, Bardeguez A, Smith E, Hughes M, Huang S, Pitt J, Watts H, Mofenson L; Pediatric AIDS Clinical Trials Group 386 Protocol Team. Pharmacokinetics of saquinavir-SGC in HIV-infected pregnant women. HIV Clin Trials. 2001 Nov-Dec;2(6):460-5. doi: 10.1310/PUY3-5JWL-FX2B-98VU.

Reference Type: BACKGROUND

PMID: 11742433 (View on PubMed)

Other Identifiers

11345

Identifier Type: REGISTRY

Identifier Source: secondary_id

PACTG 386

Identifier Type: -

Identifier Source: secondary_id

ACTG 386

Identifier Type: -

Identifier Source: org_study_id