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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000920

Collaborator

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

Enrollment

Locations

1.6

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Pregnancy	Drug: Ritonavir Drug: Saquinavir Drug: Lamivudine Drug: Zidovudine	Phase 1

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.]

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Apr 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
2	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
3	Howard Univ Hosp	Washington	District of Columbia	United States	20060
4	Univ of Miami / Jackson Memorial Hosp	Miami	Florida	United States	33136
5	Univ of Miami (Pediatric)	Miami	Florida	United States	33161
6	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois	United States	60612
7	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana	United States	701122699
8	Univ Hosp	New Orleans	Louisiana	United States	70112
9	Children's Hosp of Michigan	Detroit	Michigan	United States	48201
10	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey	United States	071032714
11	Columbia Presbyterian Med Ctr	New York	New York	United States	10032
12	Duke Univ Med Ctr	Durham	North Carolina	United States	277103499
13	Med Univ of South Carolina	Charleston	South Carolina	United States	294253312
14	Children's Hospital & Medical Center / Seattle ACTU	Seattle	Washington	United States	981050371
15	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan		Puerto Rico	009365067