A Study of Nevirapine for the Prevention of HIV Transmission From Mothers to Their Babies

NCT ID: NCT00000869

Last Updated: 2021-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2009 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2001-05-31

Brief Summary

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The purpose of this study is to see if giving the anti-HIV drug nevirapine (NVP) to HIV-positive pregnant women and their babies can help reduce the chance that a mother will give HIV to her baby during delivery. This study will also test the safety of the drug and see how well it is tolerated by the mother and her baby.

Previous studies suggest that NVP is a promising medication for blocking HIV transmission from HIV-positive mothers to their babies.

Detailed Description

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Nevirapine has several properties that make it an attractive candidate for antiretroviral therapy to interrupt HIV-1 transmission in the intrapartum and early postpartum period. The pharmacokinetic profile suggested that nevirapine would be rapidly absorbed and transferred to the infant in utero when given during labor and delivery. In addition, nevirapine has been shown to penetrate cell-free virions and inactivate virion-associated reverse transcriptase (RT) in situ. This property would be potentially useful in inactivating cell-free virions in the genital tract as well as in breast milk. These characteristics of nevirapine suggest that treatment of an HIV-infected pregnant woman in labor with an oral dose of nevirapine may provide a prophylactic level of nevirapine in the infant during the time of exposure to virus in the birth canal and/or maternal blood. In addition, nevirapine may inactivate the virion-associated RT present in cell-free virions in the genital tract or breast milk.

Women are randomized to receive either NVP or the corresponding placebo in active labor. Women are randomized at any time after their 32nd week gestation \[AS PER AMENDMENT 1/13/98: 28th week gestation\] \[AS PER AMENDMENT 2/23/00: 20th week gestation\]. The randomization is stratified using two factors: (1) use of \[AS PER AMENDMENT 2/23/00: current or anticipated\] antiretroviral therapy during the current pregnancy (no therapy at all; monotherapy for any duration; multi-agent therapy for any duration), and (2) CD4 cell count at the time of randomization (less than 200 cells; 200 - 399 cells; 400 cells or greater). Mothers are followed on study for 4 to 6 weeks postpartum. Mothers are also encouraged to follow the regimen of zidovudine (ZDV) outlined in the Office of Public Health and Science (PHS) treatment guidelines for both themselves and their infants. Infants are administered either NVP or placebo between 48 and 72 hours of life. The infant's study drug is the same as the mother's randomized treatment assignment. Infants are dosed with the study drug according to their randomization group regardless of whether the mother received the study drug. Infants are followed for 4 to 6 weeks, and are tested for HIV at 4 to 6 weeks, 3 months, and 6 months.

Conditions

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HIV Infections Pregnancy

Keywords

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Pregnancy Trimester, Third Placebos Pregnancy Pregnancy Complications, Infectious Administration, Oral Nevirapine Disease Transmission, Vertical Reverse Transcriptase Inhibitors Anti-HIV Agents

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Nevirapine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Women may be eligible for this study if they:

* Are HIV-positive.
* Are at least 20 weeks pregnant. (This study has been changed. Women no longer have to be 28 weeks pregnant.)
* Have consent from the child's father (if available).
* Are at least 13 years old (consent of parent or guardian required if under 18).

Exclusion Criteria

Women will not be eligible for this study if they:

* Have ever taken NNRTIs (nonnucleoside reverse transcriptase inhibitors).
* Are enrolled in another pregnancy treatment study.
* Are allergic to benzodiazepines.
* Have liver disease.
* Plan to breast-feed.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alejandro Dorenbaum

Role: STUDY_CHAIR

John Sullivan

Role: STUDY_CHAIR

Locations

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Univ of Alabama at Birmingham - Pediatric

Birmingham, Alabama, United States

Site Status

Univ of South Alabama

Mobile, Alabama, United States

Site Status

UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, United States

Site Status

Long Beach Memorial (Pediatric)

Long Beach, California, United States

Site Status

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

UCLA Med Ctr / Pediatric

Los Angeles, California, United States

Site Status

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, United States

Site Status

San Francisco Gen Hosp

San Francisco, California, United States

Site Status

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, United States

Site Status

Children's Hosp of Denver

Denver, Colorado, United States

Site Status

Connecticut Children's Med Ctr

Farmington, Connecticut, United States

Site Status

Univ of Connecticut / Farmington

Farmington, Connecticut, United States

Site Status

Washington Hosp Ctr

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

Site Status

Howard Univ Hosp

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

Site Status

North Broward Hosp District

Fort Lauderdale, Florida, United States

Site Status

Univ of Florida Gainesville

Gainesville, Florida, United States

Site Status

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Site Status

Univ of Miami / Jackson Memorial Hosp

Miami, Florida, United States

Site Status

Univ of Miami (Pediatric)

Miami, Florida, United States

Site Status

Med College of Georgia

Augusta, Georgia, United States

Site Status

The Med Ctr Inc

Columbus, Georgia, United States

Site Status

Cook County Hosp

Chicago, Illinois, United States

Site Status

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, United States

Site Status

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Site Status

Univ of Chicago Children's Hosp

Chicago, Illinois, United States

Site Status

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Site Status

Tulane Univ Hosp of New Orleans

New Orleans, Louisiana, United States

Site Status

Univ Hosp

New Orleans, Louisiana, United States

Site Status

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hosp

Boston, Massachusetts, United States

Site Status

Boston City Hosp / Pediatrics

Boston, Massachusetts, United States

Site Status

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Site Status

Univ of Massachusetts Med School

Worcester, Massachusetts, United States

Site Status

Children's Hosp of Michigan

Detroit, Michigan, United States

Site Status

Univ of Mississippi Med Ctr

Jackson, Mississippi, United States

Site Status

Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl

Camden, New Jersey, United States

Site Status

UMDNJ - Robert Wood Johnson Med School / Pediatrics

New Brunswick, New Jersey, United States

Site Status

St Peter's Med Ctr

New Brunswick, New Jersey, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl

Newark, New Jersey, United States

Site Status

Children's Hosp at Albany Med Ctr

Albany, New York, United States

Site Status

North Shore Univ Hosp

Great Neck, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Metropolitan Hosp Ctr

New York, New York, United States

Site Status

Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

Univ of Rochester Med Ctr

Rochester, New York, United States

Site Status

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, United States

Site Status

Bronx Lebanon Hosp Ctr

The Bronx, New York, United States

Site Status

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, United States

Site Status

Duke Univ Med Ctr

Durham, North Carolina, United States

Site Status

Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr

Durham, North Carolina, United States

Site Status

Children's Hosp of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Hosp of the Univ of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Saint Christopher's Hosp for Children

Philadelphia, Pennsylvania, United States

Site Status

Temple Univ School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Med Univ of South Carolina

Charleston, South Carolina, United States

Site Status

Regional Med Ctr at Memphis

Memphis, Tennessee, United States

Site Status

Methodist Hosp Central

Memphis, Tennessee, United States

Site Status

Saint Jude Children's Research Hosp of Memphis

Memphis, Tennessee, United States

Site Status

Vanderbilt Univ Med Ctr

Nashville, Tennessee, United States

Site Status

Children's Med Ctr of Dallas

Dallas, Texas, United States

Site Status

Texas Children's Hosp / Baylor Univ

Houston, Texas, United States

Site Status

Children's Hosp of the King's Daughters

Norfolk, Virginia, United States

Site Status

Senetara Norfolk Gen Hosp

Norfolk, Virginia, United States

Site Status

Med College of Virginia

Richmond, Virginia, United States

Site Status

Children's Hospital & Medical Center / Seattle ACTU

Seattle, Washington, United States

Site Status

Tacoma Gen Hosp

Tacoma, Washington, United States

Site Status

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, , Puerto Rico

Site Status

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

Site Status

San Juan City Hosp

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Cunningham CK, Britto P, Gelber R, Dorenbaum A, Mofenson L, Culnane M, Sullivan JL. Genotypic resistance analysis in women participating in PACTG 316 with HIV-1 RNA >400 copies/ml. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 712)

Reference Type BACKGROUND

Mirochnick M, Dorenbaum A, Cunningham-Schrader B, Cunningham C, Gelber R, Mofenson L, Sullivan J. Cord blood protease inhibitor (PI) concentrations in infants born to mothers receiving PIs. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 710)

Reference Type BACKGROUND

Dorenbaum A. Report of results of PACTG 316: an international phase III trial of standard antiretroviral (ARV) prophylaxis plus nevirapine (NVP) for prevention of perinatal HIV transmission. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no LB7)

Reference Type BACKGROUND

Cunningham CK, Chaix ML, Rekacewicz C, Britto P, Rouzioux C, Gelber RD, Dorenbaum A, Delfraissy JF, Bazin B, Mofenson L, Sullivan JL. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. J Infect Dis. 2002 Jul 15;186(2):181-8. doi: 10.1086/341300. Epub 2002 Jun 26.

Reference Type BACKGROUND
PMID: 12134253 (View on PubMed)

Mirochnick M, Dorenbaum A, Blanchard S, Cunningham CK, Gelber RD, Mofenson L, Culnane M, Sullivan JL. Predose infant nevirapine concentration with the two-dose intrapartum neonatal nevirapine regimen: association with timing of maternal intrapartum nevirapine dose. J Acquir Immune Defic Syndr. 2003 Jun 1;33(2):153-6. doi: 10.1097/00126334-200306010-00006.

Reference Type BACKGROUND
PMID: 12794547 (View on PubMed)

Cunningham CK, Balasubramanian R, Delke I, Maupin R, Mofenson L, Dorenbaum A, Sullivan JL, Gonzalez-Garcia A, Thorpe E, Rathore M, Gelber RD. The impact of race/ethnicity on mother-to-child HIV transmission in the United States in Pediatric AIDS Clinical Trials Group Protocol 316. J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):800-7. doi: 10.1097/00126334-200407010-00006.

Reference Type BACKGROUND
PMID: 15213563 (View on PubMed)

Watts DH, Balasubramanian R, Maupin RT Jr, Delke I, Dorenbaum A, Fiore S, Newell ML, Delfraissy JF, Gelber RD, Mofenson LM, Culnane M, Cunningham CK; PACTG 316 Study Team. Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316. Am J Obstet Gynecol. 2004 Feb;190(2):506-16. doi: 10.1016/j.ajog.2003.07.018.

Reference Type BACKGROUND
PMID: 14981398 (View on PubMed)

Newell ML, Huang S, Fiore S, Thorne C, Mandelbrot L, Sullivan JL, Maupin R, Delke I, Watts DH, Gelber RD, Cunningham CK; PACTG 316 Study Team. Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA. BMC Infect Dis. 2007 Jun 20;7:60. doi: 10.1186/1471-2334-7-60.

Reference Type RESULT
PMID: 17584491 (View on PubMed)

Other Identifiers

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11290

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 316

Identifier Type: -

Identifier Source: org_study_id