Clinical trial NCT00000942: A Study of Nevirapine to Prevent HIV Transmission From Mothers to Their Babies
Official title: A Phase III Randomized, Double-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: Placebos
Pregnancy
Pregnancy Complications, Infectious
Nevirapine
Disease Transmission, Vertical
Labor
Anti-HIV Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 1244
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: PREVENTION

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.

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

Detailed description: NVP has several properties that make it an attractive candidate for antiretroviral therapy to interrupt HIV-1 transmission in the intrapartum and early post-partum period. The pharmacokinetic profile suggests that NVP would be rapidly absorbed and transferred to the infant in utero when given during labor and delivery. The HIV-1 antiviral activity is rapid with significant reduction in plasma virus occurring within a few days of drug administration. In addition, NVP has been shown to penetrate cell-free virions and inactivate virion-associated 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 NVP suggest that treatment of an HIV-infected pregnant woman in labor with an oral dose of NVP may provide a prophylactic level of NVP in the infant during the time of exposure to virus in the birth canal and/or maternal blood. In addition, NVP may inactivate the virion-associated RT present in cell-free virions in the genital tract or breast milk.

Mothers are randomized to receive either a single oral dose of NVP during labor or the corresponding NVP placebo. Randomization occurs at any time after the 28th week of gestation. To assure balance between the treatment groups, the randomization is stratified using 2 factors: 1) use of antiretroviral therapy during the current pregnancy (no antiretroviral therapy at all; monotherapy \[with no multi-agent therapy\] for any duration; multi-agent therapy for any duration), and 2) CD4 cell count at the time of randomization (less than 200 cells; 200 to 399 cells; 400 cells or greater). Mothers are followed on-study for 4 to 6 weeks postpartum.

Due to the results of ACTG 076 and 185, all women for entry into ACTG 316 are encouraged to incorporate a regimen of zidovudine (ZDV) into their current treatment regimen and should continue ZDV during delivery and to their neonates (for at least 6 weeks post-birth).

Infants receive a single oral dose of NVP (or the corresponding placebo) administered 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 study drug according to their randomization group regardless of whether the mother received study drug or not. Infants are followed for 6 months of life, and are tested for HIV at birth, 4 to 6 weeks of life, 3 months of life, and 6 months of life.

Eligibility criteria: Inclusion Criteria

You may be eligible for this study if you:

* Are an HIV-positive pregnant woman.
* Have been pregnant for at least 28 weeks.
* Are at least 13 years of age (consent of parent or guardian is required if under 18).

Exclusion Criteria

You will not be eligible for this study if:

* Your baby will not live.
* You intend to breast-feed.
* You are allergic to benzodiazepines (a tranquilizer).
* You have a liver disorder.
* You have received non-nucleoside reverse transcriptase inhibitors (a class of anti-HIV drugs).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Nassau
country: Bahamas
facility: Princess Margaret Hosp
city: Lyon
country: France
facility: Hopital Hotel Dieu de Lyon
city: Nantes
country: France
facility: CHRU de Nantes
city: Napoli
country: Italy
facility: Universita Frederico II
city: Madrid
country: Spain
facility: Hosp Doce De Octubre
Study officials:
name: Alejandro Dorenbaum, MD
role: STUDY_CHAIR
name: John L. Sullivan, MD
role: STUDY_CHAIR
References:
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.