Safety and Effectiveness of Ritonavir Plus Lamivudine Plus Zidovudine in HIV-Infected Pregnant Women and Their Babies

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase I Trial of the Safety, Tolerance, and Pharmacokinetics of Oral Ritonavir Co-Administered With Lamivudine (3TC) and Zidovudine (ZDV) in HIV-1-Infected Pregnant Women and Their Infants

The purpose of this study is to see if it is safe and effective to give ritonavir (RTV) plus lamivudine (3TC) plus zidovudine (ZDV) to HIV-infected pregnant women during pregnancy and to their babies after birth.

Pregnant women who are HIV-positive are at risk of giving HIV to their babies during pregnancy or delivery. It is important to learn how to prevent HIV-positive pregnant women from giving HIV to their babies. RTV and ZDV have been shown to be safe and effective against HIV in adults. The combination of 3 anti-HIV drugs (RTV, 3TC, and ZDV) may help prevent HIV infection from mother to infant but studies are needed to determine whether they are safe and effective during pregnancy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Controlled studies of the pharmacokinetics and safety of new drugs are critical to the development of alternative therapies for the prevention of perinatal transmission of HIV-1. The dosing regimen of RTV and ZDV used to treat pregnant women in this study has been shown to be safe and effective against HIV in adults. Little is known about the metabolism and tolerance of these drugs during pregnancy, and Phase I studies are needed to determine dosage, safety, and tolerance. Protease inhibitors in combination with other antiretroviral drugs may help reduce the rate of perinatal transmission of HIV-1.

Pregnant women start with RTV (increasing gradually over a few days) plus 3TC plus ZDV until active labor. Intrapartum, women receive RTV plus 3TC plus ZDV, then postpartum (after cord clamped until 12 weeks postpartum), RTV plus 3TC plus ZDV. [AS PER AMENDMENT 2/9/99: For maternal dosing, one Combivir tablet (containing 3TC and ZDV) may be administered in place of the individual agents 3TC and ZDV. During the intrapartum period, Combivir is held and the patient follows intrapartum 3TC/ZDV dosing. During the intrapartum period, no RTV is given after the onset of active labor. During the postpartum period, RTV is begun as soon as oral intake is allowable following delivery. During the postpartum period, Combivir may be resumed. All subjects who prematurely discontinue study treatment should continue to be followed for the duration of the study.] [AS PER AMENDMENT 9/28/99: During the intrapartum period, RTV is given at the start of active labor.] Infants begin 3TC and ZDV as soon as oral intake is tolerated. Infants participate in one of two cohorts. The first four infants delivered (Cohort 1) receive RTV as a single dose between Days 8 and 12. The next six infants delivered (Cohort 2) start RTV at 2-3 days of life. The dosing schedule is based on Cohort 1 drug pharmacokinetics data. [AS PER AMENDMENT 2/9/99: Cohort 1 is expanded to seven mother/infant pairs.] [AS PER AMENDMENT 9/28/99: Cohort 1 is expanded to eight mother/infant pairs.] Both maternal and infant blood is drawn to assess drug pharmacokinetics. Cervical secretions are collected to assess presence of virus. In addition, all placentas are examined by histopathology to determine the role of placenta on preterm delivery in women receiving combination antiretroviral therapy.

Study Type

Interventional

Enrollment

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33161
        • Univ. of Miami Ped. Perinatal HIV/AIDS CRS
      • Miami, Florida, United States, 33136
        • Univ. of Miami Miller School of Medicine - Jackson Memorial Hosp.
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan NICHD CRS
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude/UTHSC CRS
      • Memphis, Tennessee, United States, 38103
        • Regional Med Ctr at Memphis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria

Women may be eligible for this study if they:

  • Are HIV-positive.
  • Are between 14 and 32 weeks pregnant.
  • Are at least 13 years old (consent of parent or guardian required if under 18).
  • Have the consent of the baby's father (if he can be reached).

Exclusion Criteria

Women will not be eligible for this study if they:

  • Are having problems with their pregnancy.
  • Have a history of problem pregnancies including miscarriages, birth defects, stillbirths, or giving birth to premature or low-birth-weight babies.
  • Have had side effects to ZDV, 3TC, or RTV.
  • Have an active opportunistic (AIDS-related) or other serious infection.
  • Have other serious conditions such as heart or lung problems, blood disorders, diabetes, or seizures.
  • Are pregnant with more than one baby (such as twins or triplets).
  • Are taking other experimental medications.
  • Are taking other anti-HIV medications.
  • Are taking certain other medications including those for cancer, blood pressure, or seizures.
  • Are abusing drugs or alcohol.
  • Are breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

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

Investigators

  • Study Chair: Gwendolyn Scott, Univ of Miami (Pediatric)
  • Study Chair: Mary Jo O'Sullivan, Univ of Miami (Pediatric)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

April 1, 2001

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

October 29, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 354
  • 10604 (Registry Identifier: DAIDS ES)
  • PACTG 354

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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