Potential adverse effects of antiretroviral therapy on the mother and fetus should be discussed during counseling. Experience to date with the administration of antiretrovirals other than ZDV during pregnancy is quite limited. Table 4.1 summarizes the potential toxic effects of these drugs.*

Several programs have been developed to identify potential risks of antiretroviral therapy administered during pregnancy or early infancy. Animal models are often used to screen for potential toxicities and teratogenic properties of antiretroviral agents before these agents are evaluated clinically in humans. While the relevance of these models to human therapy is unproven, they may be useful in identifying agents of concern. Recently, severe congenital anomalies were identified in 3 of 13 infant monkeys born to mothers who had received Efavirenz, a non-nucleoside reverse transcriptase inhibitor, during pregnancy (DuPont-Merck, 1998). The doses used in this study were those anticipated to achieve plasma concentrations similar to those achieved in humans on standard recommended doses of the drug. Congenital anomalies were not observed in any of the 13 infants of mothers treated with the vehicle control. As a result of these studies, women receiving Efavirenz are advised to avoid pregnancy.

The Phase I evaluation of combination antiretroviral regimens, including protease inhibitors, in pregnant women and young infants is now under way through the ACTG. An ACTG Phase II/III trial evaluating the efficacy of nevirapine (a non-nucleoside reverse transcriptase inhibitor) in preventing perinatal HIV transmission is also under way. All ACTG protocol participants exposed to antiretroviral agents in utero or during infancy are encouraged to enroll in ACTG protocol 219, which will evaluate them at least through age 21 for potential long-term sequelae. Several pharmaceutical companies (Glaxo Wellcome, Inc.; Hoffmann-LaRoche, Inc.; Bristol-Myers Squibb Co.; and Merck & Co., Inc.), in cooperation with the Centers for Disease Control and Prevention (CDC), maintain a registry to assess the safety of ZDV, didanosine (ddI), lamivudine (3TC), saquinavir (SAQ), stavudine (d4t), and dideoxycytidine (ddC) during pregnancy. Providers are encouraged to enroll in this registry women who receive any of these drugs during pregnancy. The registry findings did not indicate any increase in the number of birth defects after receipt of ZDV alone. No consistent pattern of birth defects that would suggest a common cause has been observed. The number of cases reported through February 1997, however, was insufficient to reliably estimate the quantitative risk of birth defects after the administration of these agents, alone or in combination, to pregnant women and their infants.

*  

In July, 1998, a high rate of prematurity was reported in a study of infants whose mothers received antiretroviral therapy during pregnancy (Lorenzi et al., 1998). The small numbers of subjects and limited information about background rates of prematurity in this study limit the ability to attribute the prematurity to the antiretroviral therapy, and the PHS treatment recommendations (CDC, 1998d) have not been changed. Ongoing perinatal trials are being monitored intensively to evaluate potential relationships between antiretroviral use and adverse pregnancy outcomes.



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