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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000888
First received: November 2, 1999
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Pregnancy
Drug: Ritonavir
Drug: Lamivudine
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 14
Study Completion Date: April 2001
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000888

Locations
United States, Florida
Univ. of Miami Ped. Perinatal HIV/AIDS CRS
Miami, Florida, United States, 33161
Univ. of Miami Miller School of Medicine - Jackson Memorial Hosp.
Miami, Florida, United States, 33136
United States, Michigan
Children's Hospital of Michigan NICHD CRS
Detroit, Michigan, United States, 48201
United States, Tennessee
Regional Med Ctr at Memphis
Memphis, Tennessee, United States, 38103
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
Investigators
Study Chair: Gwendolyn Scott Univ of Miami (Pediatric)
Study Chair: Mary Jo O'Sullivan Univ of Miami (Pediatric)
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000888     History of Changes
Other Study ID Numbers: ACTG 354, 10604, PACTG 354
Study First Received: November 2, 1999
Last Updated: May 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pregnancy
Pregnancy Complications, Infectious
Drug Therapy, Combination
Administration, Oral
Zidovudine
HIV Protease Inhibitors
Ritonavir
Disease Transmission, Vertical
Anti-HIV Agents
Fetal Blood

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Lamivudine
Ritonavir
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on April 23, 2014