Comparison of Anti-HIV Drug Combinations to Prevent Mother-to-Child Transmission of HIV

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00086359
First received: June 30, 2004
Last updated: May 31, 2013
Last verified: May 2013
  Purpose

Pregnant women infected with HIV who take anti-HIV medications during pregnancy lower the risk of passing HIV to their infants. This study will compare how well two different combinations of anti-HIV medications control HIV in pregnancy, and whether these combinations of drugs are effective in preventing HIV from being transmitted from a pregnant woman to her baby. The two combinations are abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) and zidovudine/lamivudine (ZDV/3TC) plus lopinavir/ritonavir (LPV/RTV).


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate, lamivudine, and zidovudine
Drug: Lamivudine/zidovudine
Drug: Lopinavir/ritonavir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase III Randomized Trial of the Safety and Antiretroviral Effects of Zidovudine/Lamivudine/Abacavir Versus Zidovudine/Lamivudine/Lopinavir/Ritonavir in the Prevention of Perinatal Transmission of HIV

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Proportion of women in each treatment group with virologic suppression to less than 400 copies/ml at 34th week of pregnancy (or last viral load prior to delivery, if delivery occurs before 34th week of pregnancy) while continuing on assigned therapy [ Time Frame: at Week 34 of pregnancy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Primary outcome, evaluating ART naive and ART experienced women [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • HIV-related health status of women at delivery, determined by CD4 counts and plasma HIV-1 viral load in the two treatment groups and in ART naive and ART experienced women [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • study treatment adherence and health status by self report [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • HIV-related health status of women postpartum, determined by CD4 counts and plasma HIV-1 viral load [ Time Frame: at Months 3, 6 and 12 postpartum and prior to ART treatment ] [ Designated as safety issue: Yes ]
  • development of HIV-1 genotypic resistance among women in each treatment group [ Time Frame: at delivery, Months 3, 6, and 12 postpartum, and in all cases of treatment failure ] [ Designated as safety issue: No ]
  • incidence of abnormal glucose tolerance, gestational diabetes, and abnormal lactate levels during pregnancy in each treatment group [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • incidence of anemia, hypoglycemia, abnormal liver function studies, prematurity, low birth weight, or perinatal HIV transmission among infants born to women in each treatment group [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • predictive value, sensitivity, and specificity of polymorphisms in HLA-B57, HLA-DR7, and HLA-DQ3 in identifying pregnant women at risk for development of ABC hypersensitivity [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • concentration of T cell receptor rearrangement excision DNA circles [ Time Frame: at study entry, delivery and 6 weeks postpartum ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: July 2004
Study Completion Date: September 2007
Arms Assigned Interventions
Experimental: A
One pill of abacavir/lamivudine/zidovudine twice daily
Drug: Abacavir sulfate, lamivudine, and zidovudine
one pill twice daily
Experimental: B
One pill of zidovudine/lamivudine and four pills of lopinavir/ritonavir twice daily.
Drug: Lamivudine/zidovudine
one pill twice daily
Drug: Lopinavir/ritonavir
four pills twice daily

Detailed Description:

Antiretroviral therapy (ART) in pregnancy has dramatically reduced the rates of perinatal HIV transmission. Many pregnant women infected with HIV may not meet the criteria for treatment as set forth by the Department of Health and Human Services' guidelines and would not be started on therapy if they were not pregnant. Pregnant women are prescribed a variety of treatment regimens; the optimum regimen for pregnant women who plan to discontinue therapy after delivery is unknown. An optimum regimen would account for the need for maximum viral suppression, minimal fetal toxicity, and preservation of future therapeutic options for the mother. This study will compare an all nucleoside reverse transcriptase inhibitor (NRTI) regimen of ABC/3TC/ZDV with a standard protease inhibitor (PI) regimen of LPV/RTV and 3TC/ZDV. This study was initially designed for women who plan to take antiretrovirals only while pregnant and do not meet the criteria for treatment initiation if not pregnant. However, pregnant women who have taken ART for 180 days or less or have taken ZDV monotherapy for a total of 8 weeks or less prior to entering this study are eligible for Version 2.0 of this study.

Women in this study will be randomly assigned to one of two groups. Women in Group A will receive one pill ABC/3TC/ZDV twice a day. Women in Group B will receive one pill 3TC/ZDV and 4 pills LPV/RTV twice a day. Women will take their assigned medications until they go into labor. Once in labor, women will be given zidovudine through intravenous (IV) infusion; they will stop taking oral zidovudine but will continue with their other medications. After delivery, all infants will be given zidovudine for six weeks.

Women will have study visits every 2 weeks for the first 8 weeks of treatment, and then every 4 weeks until Week 28. Depending on where a woman is in her pregnancy when she enrolls in the study, she will also have study visits at Weeks 20, 28, and 34 of her pregnancy. At each visit, women will have a medical interview, a physical exam, and an obstetrical exam; blood and urine collection will occur at these visits. Mothers will undergo a fetal ultrasound at Week 20. Adherence, health status, and behavior assessments will occur at selected visits prior to delivery.

After delivery, women will stop taking the study medications but will continue to have study visits at approximately 6, 12, 24, 36, 48, and 52 weeks after delivery. Medical history and a physical exam will occur at all visits for mothers postpartum. Blood collection will occur at every postpartum visit; urine collection will occur 12, 24, and 48 weeks postpartum; health status and behavior assessments will occur at most visits postpartum. Infants will have study visits at 2, 16, and 24 weeks after birth. A medical history, physical exam, and laboratory tests will be conducted at the infant study visits. Women will also be asked to enroll their infants in PACTG 219C, a long-term study that follows infants who are born to HIV infected mothers.

  Eligibility

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

Note: The pharmacokinetics testing portion of this study has been discontinued in Version 2.0 of this protocol.

Inclusion Criteria for Mothers:

  • HIV infected
  • Between the 12th and 30th week of pregnancy
  • Intend to continue pregnancy
  • Viral load less than 55,000 copies/ml within 30 days of study entry
  • CD4 count greater than 350 cells/ml within 30 days of study entry
  • Have not previously taken anti-HIV medications (women who have taken 8 weeks or fewer of zidovudine are still eligible) OR have taken anti-HIV medication but have been off treatment for more than 180 days
  • Intend to stop taking anti-HIV medications after pregnancy
  • Willing to have her infant tested for HIV
  • Parent or guardian willing to provide informed consent, if applicable
  • Have access to a participating site and are willing to be followed for the duration of the study

Exclusion Criteria for Mothers:

  • Chemotherapy for active cancer
  • Active opportunistic infection or severe medical condition within 14 days of study entry
  • Chronic diarrhea within 1 month of study entry or unresolved acute diarrhea within 7 days of study entry
  • Certain abnormal laboratory values
  • Diabetes mellitus when not pregnant. Participants who have gestational diabetes are not excluded.
  • Current alcohol or other substance abuse that, in the opinion of the investigator, may interfere with the study
  • Acute hepatitis within 90 days of study entry
  • Major birth defects in infant
  • Severe skin disorder (e.g., eczema or psoriasis) requiring systemic treatment
  • Require certain medications
  • Medical condition that may, in the opinion of the investigator, interfere with the study
  • Intend to breastfeed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086359

Locations
United States, California
Usc La Nichd Crs
Los Angeles, California, United States, 90033
UCSD Mother-Child-Adolescent Program CRS
San Diego, California, United States, 92103
United States, Florida
Univ. of Miami Ped. Perinatal HIV/AIDS CRS
Miami, Florida, United States, 33136
United States, Illinois
Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
Chicago, Illinois, United States, 60608
United States, New York
Bronx-Lebanon Hosp. IMPAACT CRS
Bronx, New York, United States, 10457
United States, Tennessee
Regional Med. Ctr. at Memphis
Memphis, Tennessee, United States, 38105-2794
United States, Texas
Texas Children's Hosp. CRS
Houston, Texas, United States, 77030
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico
Sponsors and Collaborators
Investigators
Study Chair: Andrew D. Hull, MD Department of Reproductive Medicine, Division of Perinatal Medicine, University of California, San Diego School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00086359     History of Changes
Other Study ID Numbers: P1039, 10046, PACTG P1039
Study First Received: June 30, 2004
Last Updated: May 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Naive
Perinatal Transmission
Mother-to-Child Transmission
MTCT
Treatment Experienced

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
Abacavir
Lamivudine, zidovudine drug combination
Ritonavir
Lopinavir
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
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014