Combination Treatment With and Without Protease Inhibitors for Women Who Begin Therapy for HIV Infection During Pregnancy

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00017719
First received: June 8, 2001
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

The best anti-HIV treatment regimen for pregnant women is not known. Protease inhibitors (PIs) are often used, but they have side effects that may be harmful for pregnant women. It is not known if treatment regimens that do not include PIs are as effective in pregnant women as those that include PIs. This trial will compare two anti-HIV treatment plans, one with and one without PIs, in women who start HIV treatment during pregnancy. The study will evaluate the effects of the anti-HIV drugs on the developing infant and prevention of mother-to-child HIV transmission during pregnancy.


Condition Intervention Phase
HIV Infections
Pregnancy
Drug: Lamivudine
Drug: Lamivudine/Zidovudine
Drug: Nelfinavir mesylate
Drug: Nevirapine
Drug: Zidovudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial of Protease Inhibitor-Including vs. Protease Inhibitor-Sparing Regimens for Women Who Initiate Therapy of HIV Infection During Pregnancy

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 who continue on original therapy with virologic suppression to less than 500 copies/ml at 34 weeks gestation (or the last viral load determination prior to delivery)
  • proportion of women in each treatment group who continue on original therapy with virologic suppression to less than 500 copies/ml at 48 weeks postpartum

Secondary Outcome Measures:
  • Proportion of women in each treatment group who continue on original therapy with virologic suppression to less than 50 copies/ml at 34 weeks gestation (or the last viral load determination prior to delivery)
  • proportion of women in each treatment group who continue on original therapy with virologic suppression to less than 50 copies/ml at 48 weeks postpartum, and to less than 500 and 50 copies/ml at 104 weeks postpartum
  • study treatment adherence and health status by self-report, correlated with predose nelfinavir or nevirapine level at 34 weeks gestation and 8 weeks postpartum
  • difference between postpartum and pregnancy 12-hour area under the concentration curve (AUC) for nevirapine
  • time of trough levels in relation to the morning dose of nevirapine and nelfinavir at 34 weeks gestation and 8 weeks postpartum and correlation of trough levels with viral load
  • incidence of HIV viral resistance by genotype among women in each treatment group at the time of virologic failure
  • incidence of abnormal glucose tolerance, gestational diabetes, and abnormal lactate levels during pregnancy in each treatment group
  • incidence of impaired glucose tolerance, diabetes, hyperinsulinemia, and elevated cholesterol and triglycerides at 8 weeks postpartum in each treatment group
  • incidence of anemia, hypoglycemia, and abnormal liver function studies among infants born to women in each treatment group
  • incidence of prematurity (less than 37 weeks), extreme prematurity (less than 32 weeks), low birth weight (less than 2.5 kg), and very low birth weight (less than 1.5 kg) among infants born to women in each treatment group
  • perinatal HIV transmission among infants born to women in each treatment group

Estimated Enrollment: 440
Study Start Date: May 2002
Study Completion Date: March 2006
Detailed Description:

The optimal treatment strategy for women who initiate antiretroviral therapy during pregnancy is not known. Although PI-based antiretroviral regimens are prescribed with increasing frequency among pregnant women, the efficacy and safety of this approach is unknown. Pregnant women are at increased risk for glucose intolerance and insulin resistance; PIs are associated with glucose intolerance. Physiologic differences between pregnant women and nonpregnant adults may alter the pharmacokinetics of antiretroviral regimens. Fetal safety considerations and effects on perinatal HIV transmission must also be considered when selecting an antiretroviral regimen for pregnant women. This trial will compare PI-based and PI-sparing antiretroviral regimens for women initiating antiretroviral therapy in pregnancy.

Women will be stratified on the basis of viral load (50,000 or less copies/ml or greater than 50,000 copies/ml) and gestational age at entry (20 or less weeks or greater than 20 weeks) and then randomized to one of two treatment groups. Group A will receive the PI nelfinavir (NFV) with zidovudine (ZDV) and lamivudine (d4T); Group B will receive nevirapine (NVP) with ZDV and d4T. Women will have clinic visits for physical and obstetrical examinations at 2, 4, 6, and 8 weeks after entry and then every 4 weeks until delivery. After delivery, infants in both groups may receive ZDV until they are 6 weeks old. Infants are evaluated for safety and to test the infant's blood for HIV-1 at birth and at Weeks 2, 8, 16, and 24.

Women will continue on assigned antiretroviral therapy postpartum and will have 11 postpartum clinic visits over a period of 2 years. Blood samples from women will be evaluated for safety and for virologic, pharmacokinetic, and metabolic studies. The first 12 women randomized to Group A will undergo a 4-hour pharmacokinetic profile at 32 to 36 weeks gestation and at 8 weeks postpartum to determine the timing of the nelfinavir trough. The first 20 women randomized to Group B will undergo an 8-hour pharmacokinetic profile at either 16 to 24 weeks or 32 to 36 weeks gestation and then again at 8 weeks postpartum to characterize pharmacokinetics of nevirapine at steady state in pregnancy and in the postpartum period.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV infected
  • 10 to 30 weeks pregnant
  • Plan to continue pregnancy
  • CD4 count less than 250 cells/mm3 within 30 days of study entry
  • HIV RNA load greater than 1,000 copies/ml within 30 days of study entry
  • Antiretroviral naive (except ZDV for 8 weeks or less, including prior pregnancy)
  • Willing to follow study requirements and plan to continue receiving anti-HIV treatment for at least 2 years after delivery
  • Understand that NFV will not be supplied by the study (except for the first 12 women in Group A)
  • Understand the study drug NVP will not be supplied after 1 year following delivery and is reasonably certain that she can obtain NVP by prescription for the second year of the study
  • Access to a participating site
  • Willing to have infant followed until 24 weeks old
  • Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

  • Alcohol or drug abuse
  • Chemotherapy for an active cancer
  • Require certain medications
  • AIDS-related opportunistic infection and/or serious bacterial infection or unstable or serious medical condition within 14 days of study entry
  • Chronic malabsorption or diarrhea
  • Diabetes, unless it only occurs during pregnancy
  • Major fetal problem or abnormality
  • Abnormal amniotic fluid volume
  • Plan to breastfeed
  • Acute hepatitis within 90 days of study entry
  • Skin problems such as psoriasis or eczema that require systemic treatment
  • Any serious disease that, in the opinion of the study official, would compromise study participation
  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: NCT00017719

  Hide Study Locations
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
UCSF Pediatric AIDS CRS
San Francisco, California, United States
Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
Torrance, California, United States, 90509
United States, Connecticut
Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
New Haven, Connecticut, United States, 06504
United States, District of Columbia
Howard Univ. Washington DC NICHD CRS
Washington, District of Columbia, United States, 20060
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, Georgia
Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases
Augusta, Georgia, United States, 30912
Columbus Regional HealthCare System, The Med. Ctr.
Columbus, Georgia, United States, 31901
United States, Illinois
Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
Chicago, Illinois, United States, 60608
Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
Chicago, Illinois, United States, 60637-1470
United States, Louisiana
Tulane/LSU Maternal/Child CRS
New Orleans, Louisiana, United States, 70112-2699
Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic
New Orleans, Louisiana, United States, 70112-2699
United States, Maryland
Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
Baltimore, Maryland, United States, 21287-4933
Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
Baltimore, Maryland, United States
United States, Massachusetts
BMC, Div. of Ped Infectious Diseases
Boston, Massachusetts, United States, 02118
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, United States, 02115
Brigham and Women's Hosp., Div. of Infectious Disease
Boston, Massachusetts, United States, 02478
Baystate Health, Baystate Med. Ctr.
Springfield, Massachusetts, United States, 01199
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States, 01655
United States, Michigan
Children's Hospital of Michigan NICHD CRS
Detroit, Michigan, United States, 48201
Univ. of Mississippi Med. Ctr Children's Hosp.
Jackson, Michigan, United States, 39213
United States, New Jersey
Rutgers - New Jersey Medical School CRS
Newark, New Jersey, United States, 07103
United States, New York
Montefiore Med. Ctr. - AECOM
Bronx, New York, United States, 19461
Bronx-Lebanon Hosp. IMPAACT CRS
Bronx, New York, United States, 10457
Nyu Ny Nichd Crs
New York, New York, United States, 10016
Columbia IMPAACT CRS
New York, New York, United States, 10032
Strong Memorial Hospital Rochester NY NICHD CRS
Rochester, New York, United States, 14642
SUNY Stony Brook NICHD CRS
Stony Brook, New York, United States, 11794
SUNY Upstate Med. Univ., Dept. of Peds.
Syracuse, New York, United States, 13210
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
Case CRS
Cleveland, Ohio, United States, 44106
MetroHealth CRS
Cleveland, Ohio, United States, 44109-1998
United States, Oregon
Oregon Health & Science Univ. - Dept. of Peds., Div. of Infectious Disease
Portland, Oregon, United States
United States, Tennessee
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 38105
Regional Med. Ctr. at Memphis
Memphis, Tennessee, United States, 38105
Vanderbilt Univ. Med. Ctr., Div. of Ped. Infectious Diseases
Nashville, Tennessee, United States, 38105
United States, Texas
Texas Children's Hosp. CRS
Houston, Texas, United States, 77030
United States, Washington
UW School of Medicine - CHRMC
Seattle, Washington, United States, 98105-0371
Univ. of Washington NICHD CRS
Seattle, Washington, United States, 98105-0371
UW Medicine - Harborview Med. Ctr., Northwest Family Ctr.
Seattle, Washington, United States, 98105-0371
Seattle Children's Hospital CRS
Seattle, Washington, United States
Bahamas
Princess Margaret Hosp. Bahamas NICHD CRS
Nassau, Bahamas
Brazil
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, Brazil
Hosp. dos Servidores do Estado CRS
Rio de Janeiro, Brazil, 22261-161
Hosp. dos Servidores Rio de Janeiro NICHD CRS
Rio de Janeiro, Brazil, 20221-903
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Investigators
Study Chair: Jane Hitti, MD, MPH Department of Obstetrics/Gynecology, University of Washington Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00017719     History of Changes
Other Study ID Numbers: P1022, 10192, ACTG P1022, PACTG P1022
Study First Received: June 8, 2001
Last Updated: November 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pregnancy Complications, Infectious
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Combivir
Treatment Naive

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
Protease Inhibitors
Nelfinavir
HIV Protease Inhibitors
Zidovudine
Nevirapine
Lamivudine
Reverse Transcriptase Inhibitors
Lamivudine, zidovudine drug combination
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antimetabolites
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014