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

A Phase III Randomized, Blinded Study of Nevirapine for the Prevention of Maternal-Fetal Transmission in Pregnant HIV-Infected Women

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Pregnancy
• Intervention / Treatment: Drug: Nevirapine

Detailed Description

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.

• Study Type: Interventional
• Enrollment: 2009
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00956
    • Ramon Ruiz Arnau Univ Hosp / Pediatrics
  • San Juan, Puerto Rico, 009367344
    • San Juan City Hosp
  • San Juan, Puerto Rico, 009365067
    • Univ of Puerto Rico / Univ Children's Hosp AIDS
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Univ of Alabama at Birmingham - Pediatric
    • Mobile, Alabama, United States, 36604
      • Univ of South Alabama
  • California
    • La Jolla, California, United States, 920930672
      • UCSD Med Ctr / Pediatrics / Clinical Sciences
    • Long Beach, California, United States, 90801
      • Long Beach Memorial (Pediatric)
    • Los Angeles, California, United States, 90033
      • Los Angeles County - USC Med Ctr
    • Los Angeles, California, United States, 905022004
      • Harbor - UCLA Med Ctr / UCLA School of Medicine
    • Los Angeles, California, United States, 900951752
      • UCLA Med Ctr / Pediatric
    • San Francisco, California, United States, 94110
      • San Francisco Gen Hosp
    • San Francisco, California, United States, 941430105
      • UCSF / Moffitt Hosp - Pediatric
  • Colorado
    • Denver, Colorado, United States, 802181088
      • Children's Hosp of Denver
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • Univ of Connecticut / Farmington
    • Farmington, Connecticut, United States, 060303805
      • Connecticut Children's Med Ctr
  • District of Columbia
    • Washington, District of Columbia, United States, 200102931
      • Washington Hosp Ctr
    • Washington, District of Columbia, United States, 20060
      • Howard Univ Hosp
  • Florida
    • Fort Lauderdale, Florida, United States, 33311
      • North Broward Hosp District
    • Gainesville, Florida, United States, 32610
      • Univ of Florida Gainesville
    • Jacksonville, Florida, United States, 32209
      • Univ of Florida Health Science Ctr / Pediatrics
    • Miami, Florida, United States, 33161
      • Univ of Miami (Pediatric)
    • Miami, Florida, United States, 33136
      • Univ of Miami / Jackson Memorial Hosp
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Med College of Georgia
    • Columbus, Georgia, United States, 31901
      • The Med Ctr Inc
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
    • Chicago, Illinois, United States, 606143394
      • Chicago Children's Memorial Hosp
    • Chicago, Illinois, United States, 606371470
      • Univ of Chicago Children's Hosp
    • Chicago, Illinois, United States, 60612
      • Univ of Illinois College of Medicine / Pediatrics
  • Louisiana
    • New Orleans, Louisiana, United States, 701122699
      • Tulane Univ / Charity Hosp of New Orleans
    • New Orleans, Louisiana, United States, 701122699
      • Tulane Univ Hosp of New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Univ Hosp
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ of Maryland at Baltimore / Univ Med Ctr
    • Baltimore, Maryland, United States, 212874933
      • Johns Hopkins Hosp - Pediatric
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hosp
    • Boston, Massachusetts, United States, 021155724
      • Children's Hosp of Boston
    • Boston, Massachusetts, United States, 02118
      • Boston City Hosp / Pediatrics
    • Springfield, Massachusetts, United States, 01199
      • Baystate Med Ctr of Springfield
    • Worcester, Massachusetts, United States, 016550001
      • Univ of Massachusetts Med School
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hosp of Michigan
  • Mississippi
    • Jackson, Mississippi, United States, 39213
      • Univ of Mississippi Med Ctr
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl
    • New Brunswick, New Jersey, United States, 089030019
      • UMDNJ - Robert Wood Johnson Med School / Pediatrics
    • New Brunswick, New Jersey, United States, 08903
      • St Peter's Med Ctr
    • Newark, New Jersey, United States, 071032714
      • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
    • Newark, New Jersey, United States, 07103
      • Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
  • New York
    • Albany, New York, United States, 12208
      • Children's Hosp at Albany Med Ctr
    • Bronx, New York, United States, 10461
      • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
    • Bronx, New York, United States, 10457
      • Bronx Lebanon Hosp Ctr
    • Great Neck, New York, United States, 11021
      • North Shore Univ Hosp
    • New York, New York, United States, 10016
      • Bellevue Hosp / New York Univ Med Ctr
    • New York, New York, United States, 10029
      • Metropolitan Hosp Ctr
    • New York, New York, United States, 10032
      • Columbia Presbyterian Med Ctr
    • Rochester, New York, United States, 146420001
      • Univ of Rochester Med Ctr
    • Syracuse, New York, United States, 13210
      • SUNY Health Sciences Ctr at Syracuse / Pediatrics
  • North Carolina
    • Durham, North Carolina, United States, 277103499
      • Duke Univ Med Ctr
    • Durham, North Carolina, United States, 27710
      • Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 191044318
      • Children's Hosp of Philadelphia
    • Philadelphia, Pennsylvania, United States, 191341095
      • Saint Christopher's Hosp for Children
    • Philadelphia, Pennsylvania, United States, 191341095
      • Temple Univ School of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Hosp of the Univ of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 294253312
      • Med Univ of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 381052794
      • Saint Jude Children's Research Hosp of Memphis
    • Memphis, Tennessee, United States, 38103
      • Regional Med Ctr at Memphis
    • Memphis, Tennessee, United States, 381052794
      • Methodist Hosp Central
    • Nashville, Tennessee, United States, 372322581
      • Vanderbilt Univ Med Ctr
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Med Ctr of Dallas
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp / Baylor Univ
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hosp of the King's Daughters
    • Norfolk, Virginia, United States, 23507
      • Senetara Norfolk Gen Hosp
    • Richmond, Virginia, United States, 23219
      • Med College of Virginia
  • Washington
    • Seattle, Washington, United States, 981050371
      • Children's Hospital & Medical Center / Seattle ACTU
    • Tacoma, Washington, United States, 98405
      • Tacoma Gen Hosp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Alejandro Dorenbaum; Study Chair: John Sullivan

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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)
• 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)
• 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)
• 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.
• 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.

Study record dates

Study Major Dates

• Study Completion (Actual): May 1, 2001

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Nevirapine; Disease Transmission, Vertical; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Pregnancy; Placebos; Pregnancy Trimester, Third; Pregnancy Complications, Infectious; Administration, Oral
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine
• Other Study ID Numbers: ACTG 316; 11290 (Registry Identifier: DAIDS ES Registry Number)