Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
Primary Purpose
Acquired Immunodeficiency Syndrome, Disease Transmission, Vertical, HIV Infections
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
immunoglobulins
Sponsored by
About this trial
This is an interventional prevention trial for Acquired Immunodeficiency Syndrome
Eligibility Criteria
HIV-positive, asymptomatic, pregnant women with CD4 concentrations of 500 or less and their infants.
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00000590
First Posted
October 27, 1999
Last Updated
April 13, 2016
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT00000590
Brief Title
Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2005
Overall Recruitment Status
Completed
Study Start Date
September 1991 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 1996 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
5. Study Description
Brief Summary
To determine if HIV hyperimmune globulin (HIVIG) given to HIV-positive pregnant women during the second and third trimester of pregnancy reduced the likelihood of maternal-fetal HIV transmission. Conducted in collaboration with the National Institute of Child Health and Human Development and the National Institute of Allergy and Infectious Diseases. The trial was Pediatric ACTG Protocol 185.
Detailed Description
BACKGROUND:
The HIV epidemic in the United States has changed its course in the past few years. The main risk group of the past, homosexual males, has reduced numbers of new infections because of education and prevention. Other groups, including intravenous drug abusers, disadvantaged urban socioeconomic classes and adolescents, continue to be infected and to transmit HIV by needle sharing and/or unprotected heterosexual activity. Many of these newly infected individuals are women of child-bearing age. These women in turn infect their children. The Centers for Disease Control estimates that there will be 2,000 infected infants born to 6,000 HIV-positive mothers annually in the United States.
Over the past few years, several studies have identified the risk of maternal-fetal transmission of HIV by seropositive mothers. The risk is close to 30 percent. However, for reasons not yet understood, the risk appears to be higher in Africa, approaching 40 percent, and lower in Europe, approaching 16 percent. Factors influencing maternal-fetal transmission of HIV are not well defined but may include the clinical state of the mother, plasma p24 antigen positivity of the mother, viral load, prior pregnancy associated with maternal-fetal HIV transmission, absence of maternal epitope specific and/or high affinity gp120 antibodies, or prematurity.
The results of a Phase III, multicenter, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy, safety, and tolerance of zidovudine for the prevention of HIV transmission from infected pregnant women to their infants (ACTG protocol 076) provided for the first time proof of the concept that a preventive intervention can reduce vertical HIV transmission (47). Based on analysis of data for 364 evaluable births, zidovudine (ZDV or AZT) treatment according to the regimen employed in ACTG 076 appeared to reduce the risk of HIV transmission by two thirds, from 25.5 percent to 8.3 percent. Eligible subjects were HIV-infected pregnant women who had received no antiretroviral therapy during their current pregnancy, who had no maternal clinical indications for antiretroviral therapy, and who had CD4+ T-lymphocyte counts above 200 per microliter at study entry.
Efficacy of ZDV for reduction of vertical HIV transmission in women with advanced HIV disease who are already receiving antiretroviral treatment according to current clinical indications for their own health, or with CD4+ T-lymphocyte counts of 200 per microliter or below, or both was not evaluated in ACTG 076.
Administration of an antiretroviral agent to a pregnant woman in theory could reduce the risk of neonatal infection by reducing the exposure of the fetus to maternal virus, or by prophylaxis of the fetus prior to exposure. Because it is postulated that intense exposure of a potentially uninfected fetus to HIV present in maternal blood and genital tract secretions occurs during parturition, the design of this study includes intrapartum administration of ZDV followed by six weeks of oral ZDV to the infant.
An identical regimen for ZDV administration was employed in ACTG Protocol 076.
Pediatric ACTG Protocol 185 evaluated the hypothesis that in HIV-infected pregnant women receiving oral ZDV for medical indications, HIVIG administered monthly beginning at 20-30 weeks gestation in combination with intravenous ZDV intrapartum, together with a single newborn dose of HIVIG within 12 hours after birth in combination with six weeks of newborn oral ZDV, would reduce vertical HIV transmission compared with IVIG administered identically as a control agent.
DESIGN NARRATIVE:
Randomized, double-blind, controlled. Approximately half of the women were given intravenous HIVIG every four weeks until delivery. The other half received standard intravenous immunoglobulin (IVIG) without anti-HIV antibody. Both groups received AZT. A similar dose of HIVIG or IVIG was given to the newborn infant within 12 hours of birth. Each infant of a multiple birth received the mother's randomized study drug. Infant blood samples were taken at birth and at several intervals during the first 24 months of life to determine the infants' HIV status by p24 antigen assays, plasma viremia, or HIV co-culture assays. An existing NICHD contract with Westat, Inc. was used to conduct the trial. Westat, the study coordinating center subcontracted to 25 NICHD clinical trial units. An approximately similar number of NIAID clinical trial units also participated in the trial. As of February 1, 1996, there were 51 clinical trial units participating. Data analysis was performed by Westat. In 1993, NHLBI contracted with North American Biologics to supply HIVIG. The trial ended in December, 1996.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acquired Immunodeficiency Syndrome, Disease Transmission, Vertical, HIV Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Masking
Double
Allocation
Randomized
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
immunoglobulins
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
HIV-positive, asymptomatic, pregnant women with CD4 concentrations of 500 or less and their infants.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Durako
Organizational Affiliation
Westat, Inc
12. IPD Sharing Statement
Citations:
PubMed Identifier
9203648
Citation
Lambert JS, Mofenson LM, Fletcher CV, Moye J Jr, Stiehm ER, Meyer WA 3rd, Nemo GJ, Mathieson BJ, Hirsch G, Sapan CV, Cummins LM, Jimenez E, O'Neill E, Kovacs A, Stek A. Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. Pediatric AIDS Clinical Trials Group Protocol 185 Pharmacokinetic Study Group. J Infect Dis. 1997 Feb;175(2):283-91. doi: 10.1093/infdis/175.2.283.
Results Reference
background
PubMed Identifier
10432323
Citation
Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA 3rd, Whitehouse J, Moye J Jr, Reichelderfer P, Harris DR, Fowler MG, Mathieson BJ, Nemo GJ. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med. 1999 Aug 5;341(6):385-93. doi: 10.1056/NEJM199908053410601.
Results Reference
background
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
http://biolincc.nhlbi.nih.gov/studies/pactg/
Available IPD/Information Identifier
PACTG
Available IPD/Information Comments
NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://biolincc.nhlbi.nih.gov/studies/pactg/
Available IPD/Information Type
Manual of Procedures
Available IPD/Information URL
http://biolincc.nhlbi.nih.gov/studies/pactg/
Learn more about this trial
Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
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