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

NCT ID: NCT00017719

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-05-31
• Study Completion Date: 2006-03-31

Brief Summary

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.

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.

Conditions

HIV Infections; Pregnancy

Keywords

Pregnancy Complications, Infectious; HIV Protease Inhibitors; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; Combivir; Treatment Naive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Lamivudine

Intervention Type: DRUG

Lamivudine/Zidovudine

Intervention Type: DRUG

Nelfinavir mesylate

Intervention Type: DRUG

Nevirapine

Intervention Type: DRUG

Zidovudine

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 14 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jane Hitti, MD, MPH

Role: STUDY_CHAIR

Department of Obstetrics/Gynecology, University of Washington Medical Center

Locations

Usc La Nichd Crs

Los Angeles, California, United States

UCSD Mother-Child-Adolescent Program CRS

San Diego, California, United States

UCSF Pediatric AIDS CRS

San Francisco, California, United States

Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases

Torrance, California, United States

Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease

New Haven, Connecticut, United States

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, United States

Univ. of Miami Miller School of Medicine - Jackson Memorial Hosp.

Miami, Florida, United States

Univ. of Miami Ped. Perinatal HIV/AIDS CRS

Miami, Florida, United States

Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases

Augusta, Georgia, United States

Columbus Regional HealthCare System, The Med. Ctr.

Columbus, Georgia, United States

Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program

Chicago, Illinois, United States

Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease

Chicago, Illinois, United States

Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic

New Orleans, Louisiana, United States

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, United States

Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases

Baltimore, Maryland, United States

Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology

Baltimore, Maryland, United States

HMS - Children's Hosp. Boston, Div. of Infectious Diseases

Boston, Massachusetts, United States

BMC, Div. of Ped Infectious Diseases

Boston, Massachusetts, United States

Brigham and Women's Hosp., Div. of Infectious Disease

Boston, Massachusetts, United States

Baystate Health, Baystate Med. Ctr.

Springfield, Massachusetts, United States

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, United States

Univ. of Mississippi Med. Ctr Children's Hosp.

Jackson, Michigan, United States

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, United States

Nyu Ny Nichd Crs

New York, New York, United States

Columbia IMPAACT CRS

New York, New York, United States

Strong Memorial Hospital Rochester NY NICHD CRS

Rochester, New York, United States

SUNY Stony Brook NICHD CRS

Stony Brook, New York, United States

SUNY Upstate Med. Univ., Dept. of Peds.

Syracuse, New York, United States

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, United States

Montefiore Med. Ctr. - AECOM

The Bronx, New York, United States

DUMC Ped. CRS

Durham, North Carolina, United States

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Case CRS

Cleveland, Ohio, United States

MetroHealth CRS

Cleveland, Ohio, United States

Oregon Health & Science Univ. - Dept. of Peds., Div. of Infectious Disease

Portland, Oregon, United States

Regional Med. Ctr. at Memphis

Memphis, Tennessee, United States

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Vanderbilt Univ. Med. Ctr., Div. of Ped. Infectious Diseases

Nashville, Tennessee, United States

Texas Children's Hosp. CRS

Houston, Texas, United States

Univ. of Washington NICHD CRS

Seattle, Washington, United States

UW Medicine - Harborview Med. Ctr., Northwest Family Ctr.

Seattle, Washington, United States

UW School of Medicine - CHRMC

Seattle, Washington, United States

Seattle Children's Hospital CRS

Seattle, Washington, United States

SOM Federal University Minas Gerais Brazil NICHD CRS

Belo Horizonte, Minas Gerais, Brazil

Hosp. dos Servidores Rio de Janeiro NICHD CRS

Rio de Janeiro, , Brazil

Hosp. dos Servidores do Estado CRS

Rio de Janeiro, , Brazil

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Princess Margaret Hosp. Bahamas NICHD CRS

Nassau, , The Bahamas

Countries

United States; Brazil; Puerto Rico; The Bahamas

References

Loutfy MR, Walmsley SL. Treatment of HIV infection in pregnant women: antiretroviral management options. Drugs. 2004;64(5):471-88. doi: 10.2165/00003495-200464050-00002.

Reference Type: BACKGROUND

PMID: 14977385 (View on PubMed)

Moodley J, Moodley D. Management of human immunodeficiency virus infection in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2005 Apr;19(2):169-83. doi: 10.1016/j.bpobgyn.2004.10.007. Epub 2004 Dec 15.

Reference Type: BACKGROUND

PMID: 15778108 (View on PubMed)

Hitti J, Frenkel LM, Stek AM, Nachman SA, Baker D, Gonzalez-Garcia A, Provisor A, Thorpe EM, Paul ME, Foca M, Gandia J, Huang S, Wei LJ, Stevens LM, Watts DH, McNamara J; PACTG 1022 Study Team. Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022. J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):772-6. doi: 10.1097/00126334-200407010-00002.

Reference Type: RESULT

PMID: 15213559 (View on PubMed)

Capparelli EV, Aweeka F, Hitti J, Stek A, Hu C, Burchett SK, Best B, Smith E, Read JS, Watts H, Nachman S, Thorpe EM Jr, Spector SA, Jimenez E, Shearer WT, Foca M, Mirochnick M; PACTG 1026S Study Team; PACTG P1022 Study Team. Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics. HIV Med. 2008 Apr;9(4):214-20. doi: 10.1111/j.1468-1293.2008.00553.x.

Reference Type: RESULT

PMID: 18366444 (View on PubMed)

Other Identifiers

10192

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG P1022

Identifier Type: -

Identifier Source: secondary_id

PACTG P1022

Identifier Type: -

Identifier Source: secondary_id

P1022

Identifier Type: -

Identifier Source: org_study_id