with zidovudine (ZDV; also known as AZT). Those receiving ZDV had a transmission rate of 7.6% compared to 22.6% for those who received placebo (Connor et al., 1994). In this study, therapy consisted of oral administration of ZDV five times per day during pregnancy, intravenous administration of ZDV to the mother during delivery, and six weeks of postnatal treatment of the infant with oral ZDV. The only observed short-term toxicity in ZDV treated infants was anemia, which was not clinically significant. While the risk of vertical HIV transmission in this study was directly correlated with maternal blood viral load and indirectly correlated with maternal CD4 count, the treatment effect was independent of maternal viral load and CD4 count (Sperling et al., 1996).
Studies conducted in the United States and Europe indicate widespread acceptance of the recommended ZDV regimen, and report resultant reductions in transmission rates to between 3% and 10% (Fiscus et al., 1996; Mayaux et al., 1997). In ACTG 185 (AIDS Clinical Trials Group protocol number 185), the ACTG 076 regimen was administered to women with advanced HIV infection and their infants; the perinatal HIV transmission rate was 4.8% (Mofenson, 1998).
The extent to which each component of the ACTG 076 regimen (i.e., the prenatal and intrapartum therapy of the mother and the postpartum therapy of the infant) contributes to this success is unclear. Receipt of only part of the ACTG 076 regimen may be associated with decreased risk of perinatal transmission (Birkhead et al., 1998). Several trials evaluating the efficacy of shorter and less intensive antiretroviral regimens are in progress. In Thailand, the use of short-course oral ZDV administered during the last two weeks of pregnancy and during labor and delivery resulted in a significant decline in HIV perinatal transmission. The estimated HIV transmission risks for placebo and ZDV groups were 18.6% and 9.2%, respectively, representing a 51% decrease in transmission risk (CDC, 1998a).
The most recent Public Health Service Task Force recommendations for the use of antiretroviral drugs among HIV-infected pregnant women in the United States have updated the 1994 guidelines, which were based on the findings of ACTG 076 (CDC, 1998d). Advances in the understanding of the pathogenesis of HIV infection have resulted in recent changes in the standard recommended antiretroviral therapy in HIV-infected adults. Combination drug regimens to maximally suppress the virus are now recommended (CDC, 1998e). Although considerations associated with pregnancy may affect decisions regarding the timing and choice of therapy, pregnancy is not a reason to defer standard combination antiretroviral therapy. It is recommended that offering antiretroviral therapy to HIV-infected women during pregnancy—whether primarily to treat HIV infection, to reduce perinatal transmission, or both—be accompanied by a discussion of the known and unknown potential benefits and risks of such therapy to the woman and infant. Optimal antiretroviral regimens should be discussed and offered to an HIV-infected woman and ZDV prophylaxis for perinatal transmission should be incorporated into those regimens whenever possible (CDC, 1998d).