[ABSTRACT:] Background: Prophylaxis guidelines for perinatal HIV transmission risk reduction are modeled after ACTG 076 and include fetal antiretroviral exposure (maternal AZT after then 1st trimester and through labor) and neonatal antiretroviral exposure (infant therapy during the first 6 weeks of life). Two recent studies of AZT use in parturient mice have had differing results: in one, high dose AZT use in the 3rd trimester was associated with liver, lung and genitourinary tumors in offspring; in the other, with lower dose AZT use in pregnant mice and their offspring, no tumors were observed. To assess short-term risk for tumors in human infants, we examined infants with known fetal and/or neonatal AZT exposure.

Methods: Infants with perinatal HIV and antiretroviral exposure (fetal/neonatal AZT) enrolled into ACTG 219 (for this analysis, only 076 enrollees with subsequent enrollment in 219, a long-term followup study, are included) or WITS were assessed. Clinical (gastrointestinal, genitourinary, pulmonary, lymphatic and other systems) and demographic data reported through 5-6/96 were assessed by collective and individual cohort (ACTG or WITS).

Results: The total number of infants with fetal and/or neonatal AZT exposure was 734. Infant sex was equally distributed (females 50%; males 50%). Infant race/ethnicity was 47% Black, 34% Hispanic, 14% White/non-Hispanic and 5% other. Infant followup ranged from 1 month - 6 years; median followup by cohort was 11.4 months (WITS) and 37.8 months (ACTG 076/219). For the WITS cohort (n=619), 98% of infants were born to mothers with gestational AZT use, 91% were born to mothers receiving AZT during delivery and 76% of infants received AZT after birth. For the ACTG 076/219 cohort (n=115), 97% of infants were exposed to AZT before and after birth. No tumors were identified in any of the 734 infants with known AZT exposure.

Conclusions: No short-term evidence for AZT-related carcinogenicity was observed in [approx.] 750 infants. Because statistical power of this analysis is limited by relatively short followup (1 month-6 years), infants with AZT exposure should be followed longitudinally and in a standardized fashion to allow for continued evaluation of any potential adverse consequences of AZT exposure, including the potential for AZT transplacental carcinogenicity.

Presenting author: Hanson IC, Baylor College of Medicine, Houston, TX.

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