Clinical trial NCT00000869: A Study of Nevirapine for the Prevention of HIV Transmission From Mothers to Their Babies
Official title: A Phase III Randomized, Blinded Study of Nevirapine for the Prevention of Maternal-Fetal Transmission in Pregnant HIV-Infected Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Pregnancy
Keywords: Pregnancy Trimester, Third
Placebos
Pregnancy
Pregnancy Complications, Infectious
Administration, Oral
Nevirapine
Disease Transmission, Vertical
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 2009
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham - Pediatric
state: Alabama
city: Mobile
country: United States
facility: Univ of South Alabama
state: Alabama
city: La Jolla
country: United States
facility: UCSD Med Ctr / Pediatrics / Clinical Sciences
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial (Pediatric)
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA Med Ctr / Pediatric
state: California
city: Los Angeles
country: United States
facility: Harbor - UCLA Med Ctr / UCLA School of Medicine
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
state: California
city: Denver
country: United States
facility: Children's Hosp of Denver
state: Colorado
city: Farmington
country: United States
facility: Connecticut Children's Med Ctr
state: Connecticut
city: Farmington
country: United States
facility: Univ of Connecticut / Farmington
state: Connecticut
city: Washington
country: United States
facility: Washington Hosp Ctr
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: North Broward Hosp District
state: Florida
city: Gainesville
country: United States
facility: Univ of Florida Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Univ of Florida Health Science Ctr / Pediatrics
state: Florida
city: Miami
country: United States
facility: Univ of Miami / Jackson Memorial Hosp
state: Florida
city: Miami
country: United States
facility: Univ of Miami (Pediatric)
state: Florida
city: Augusta
country: United States
facility: Med College of Georgia
state: Georgia
city: Columbus
country: United States
facility: The Med Ctr Inc
state: Georgia
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Univ of Illinois College of Medicine / Pediatrics
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's Memorial Hosp
state: Illinois
city: Chicago
country: United States
facility: Univ of Chicago Children's Hosp
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ / Charity Hosp of New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Tulane Univ Hosp of New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Univ Hosp
state: Louisiana
city: Baltimore
country: United States
facility: Univ of Maryland at Baltimore / Univ Med Ctr
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp - Pediatric
state: Maryland
city: Boston
country: United States
facility: Children's Hosp of Boston
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp
state: Massachusetts
city: Boston
country: United States
facility: Boston City Hosp / Pediatrics
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Worcester
country: United States
facility: Univ of Massachusetts Med School
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hosp of Michigan
state: Michigan
city: Jackson
country: United States
facility: Univ of Mississippi Med Ctr
state: Mississippi
city: Camden
country: United States
facility: Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl
state: New Jersey
city: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson Med School / Pediatrics
state: New Jersey
city: New Brunswick
country: United States
facility: St Peter's Med Ctr
state: New Jersey
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: Newark
country: United States
facility: Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
state: New Jersey
city: Albany
country: United States
facility: Children's Hosp at Albany Med Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Great Neck
country: United States
facility: North Shore Univ Hosp
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Metropolitan Hosp Ctr
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Med Ctr
state: New York
city: Syracuse
country: United States
facility: SUNY Health Sciences Ctr at Syracuse / Pediatrics
state: New York
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Durham
country: United States
facility: Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hosp of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hosp of the Univ of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hosp for Children
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Univ School of Medicine
state: Pennsylvania
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Regional Med Ctr at Memphis
state: Tennessee
city: Memphis
country: United States
facility: Methodist Hosp Central
state: Tennessee
city: Memphis
country: United States
facility: Saint Jude Children's Research Hosp of Memphis
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Univ Med Ctr
state: Tennessee
city: Dallas
country: United States
facility: Children's Med Ctr of Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
city: Norfolk
country: United States
facility: Children's Hosp of the King's Daughters
state: Virginia
city: Norfolk
country: United States
facility: Senetara Norfolk Gen Hosp
state: Virginia
city: Richmond
country: United States
facility: Med College of Virginia
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital & Medical Center / Seattle ACTU
state: Washington
city: Tacoma
country: United States
facility: Tacoma Gen Hosp
state: Washington
city: Bayamon
country: Puerto Rico
facility: Ramon Ruiz Arnau Univ Hosp / Pediatrics
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico / Univ Children's Hosp AIDS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
Study officials:
name: Alejandro Dorenbaum
role: STUDY_CHAIR
name: John Sullivan
role: STUDY_CHAIR
References:
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)
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)
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)
citation: 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.
citation: 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.
citation: 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.
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. doi: 10.1016/j.ajog.2003.07.018.
citation: 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.