linked high maternal viral loads to increased risk of HIV perinatal transmission (Borkowsky et al., 1994; Weiser et al., 1994; Dickover et al., 1996; Cao et al., 1997; Thea et al., 1997). In aggregate, however, there is no identified absolute viral threshold value that can discriminate between transmitters and nontransmitters. Transmission may be observed across the full range of viral levels.

Maternal immune depletion also appears to correlate with vertical HIV transmission. Several cohort studies have documented an increased risk of vertical transmission with maternal AIDS or lowered CD4 T-cell counts (Study, 1994; Landesman et al., 1996). Maternal HIV specific immunity may also be important. A reduced risk of transmission has been reported from women with high titers of serum antibodies capable of neutralizing their own viral strains in vitro (Scarlatti et al., 1993). Others, however, have not found any association between maternal neutralizing antibody titers and transmission (Husson et al., 1995). Little is known regarding the potential role of maternal HIV cell-mediated immunity (e.g., HIV specific cytotoxic T-lymphocytes) in protection from transmission.

Recently, an abnormality in a cell surface receptor for HIV (CCR-5) was identified in uninfected adult individuals at high risk for infection through sexual or parental exposure (reviewed in D'Souza and Harden, 1996). Lymphocytes from these individuals were relatively resistant to infection with primary HIV isolates in vitro, suggesting that the defect in the co-receptor may have protected these individuals from infection. The frequency of the homozygous deletion is approximately 1% in Caucasians. It appears to be extremely rare in Asian and African populations. Heterozygous individuals do not appear to be protected from infection. Studies are currently in progress to determine to what extent mutations in infant CCR-5 alleles and other cellular HIV co-receptors may influence perinatal HIV transmission.

Other sexually transmitted infections may increase the risk of perinatal HIV transmission. An increased risk of vertical HIV transmission with maternal vitamin A deficiency has been reported (Semba et al., 1994). Duration of membrane rupture, hemorrhage during labor, chorioamnionitis, and invasive procedures during delivery have all been associated with an increased risk of perinatal HIV transmission (Minkoff et al., 1995; Landesman et al., 1996; Mandlebrot et al., 1996).

Strategies To Prevent Perinatal HIV Transmission

Recent advances in our understanding of the timing and pathogenesis of vertical HIV infection have led to the evaluation of a variety of strategies to prevent vertical HIV transmission, including the management of maternal co-infections, maternal nutritional intervention, bypassing the route of exposure, maternal and infant antiretroviral therapy, and vaccination.

The primary focus has been on the use of perinatal antiretroviral therapy to prevent vertical HIV transmission. Recently, a profound and significant reduction in vertical HIV transmission was observed in mother-infant pairs treated



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