Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
Condition: Acquired Immunodeficiency Syndrome; Disease Transmission, Vertical; HIV Infections
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): immunoglobulins
Intervention type(s): Drug
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies
Allocation: Randomized
Masking: Double
Primary purpose: Prevention