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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000869
• Other study ID #: ACTG 316
• Secondary ID: 11290
• Status: Completed
• Phase: Phase 3
• Est. completion date: May 2001

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2009
• Est. completion date: May 2001
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections
• Pregnancy

Intervention

Drug:
• Nevirapine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
United States	Children's Hosp at Albany Med Ctr	Albany	New York
United States	Med College of Georgia	Augusta	Georgia
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Univ of Alabama at Birmingham - Pediatric	Birmingham	Alabama
United States	Boston City Hosp / Pediatrics	Boston	Massachusetts
United States	Brigham and Women's Hosp	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl	Camden	New Jersey
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Chicago Children's Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	The Med Ctr Inc	Columbus	Georgia
United States	Children's Med Ctr of Dallas	Dallas	Texas
United States	Children's Hosp of Denver	Denver	Colorado
United States	Children's Hosp of Michigan	Detroit	Michigan
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr	Durham	North Carolina
United States	Connecticut Children's Med Ctr	Farmington	Connecticut
United States	Univ of Connecticut / Farmington	Farmington	Connecticut
United States	North Broward Hosp District	Fort Lauderdale	Florida
United States	Univ of Florida Gainesville	Gainesville	Florida
United States	North Shore Univ Hosp	Great Neck	New York
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	Univ of Mississippi Med Ctr	Jackson	Mississippi
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California
United States	Long Beach Memorial (Pediatric)	Long Beach	California
United States	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCLA Med Ctr / Pediatric	Los Angeles	California
United States	Methodist Hosp Central	Memphis	Tennessee
United States	Regional Med Ctr at Memphis	Memphis	Tennessee
United States	Saint Jude Children's Research Hosp of Memphis	Memphis	Tennessee
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Univ of Miami / Jackson Memorial Hosp	Miami	Florida
United States	Univ of South Alabama	Mobile	Alabama
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
United States	St Peter's Med Ctr	New Brunswick	New Jersey
United States	UMDNJ - Robert Wood Johnson Med School / Pediatrics	New Brunswick	New Jersey
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Tulane Univ Hosp of New Orleans	New Orleans	Louisiana
United States	Univ Hosp	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Metropolitan Hosp Ctr	New York	New York
United States	Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	Children's Hosp of the King's Daughters	Norfolk	Virginia
United States	Senetara Norfolk Gen Hosp	Norfolk	Virginia
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Hosp of the Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania
United States	Temple Univ School of Medicine	Philadelphia	Pennsylvania
United States	Med College of Virginia	Richmond	Virginia
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	San Francisco Gen Hosp	San Francisco	California
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Children's Hospital & Medical Center / Seattle ACTU	Seattle	Washington
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York
United States	Tacoma Gen Hosp	Tacoma	Washington
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Washington Hosp Ctr	Washington	District of Columbia
United States	Univ of Massachusetts Med School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (8)

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. — View Citation

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)

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. Epub 2002 Jun 26. — View Citation

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. — View Citation

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)

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 betw — View Citation

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. — View Citation

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