Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome; Disease Transmission, Vertical
• Intervention / Treatment: Drug: immunoglobulins

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.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

HIV-positive, asymptomatic, pregnant women with CD4 concentrations of 500 or less and their infants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Masking: DOUBLE

Collaborators and Investigators

• 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)
• Investigators: Steven Durako, Westat, Inc

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 1991
• Study Completion: December 1, 1996

Study Registration Dates

• First Submitted: October 27, 1999
• First Submitted That Met QC Criteria: October 27, 1999
• First Posted (Estimate): October 28, 1999

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: April 13, 2016
• Last Verified: March 1, 2005

More Information

Terms related to this study

• 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; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: 310

Plan for Individual participant data (IPD)

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: PACTG
   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.
2. Study Protocol
3. Manual of Procedures