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

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.