Does perinatal antiretroviral therapy create an iatrogenic cancer risk?

Antiretroviral therapy is highly effective in reducing vertical transfer of HIV infection, sparing many thousands of children premature death from AIDS. However, accumulating evidence indicates that perinatal exposure to antiretroviral agents may place them at elevated risk of developing cancer later in life, owing to potential carcinogenic effects of the agents. An initial experimental evaluation clearly demonstrated that AZT was a genotoxin and transplacental carcinogen of intermediate potency in CD-1 mice. This issue of Environmental and Molecular Mutagenesis contains reports of recent studies designed to confirm and extend earlier findings, and to provide further perspective that will facilitate development of strategies through which the adverse effects might be mitigated. The studies focused on various aspects of the genotoxicity and carcinogenicity of antiretroviral agents, including: mutagenesis in several in vitro experimental systems; mutations and clastogenic effects induced by transplacental administration in mice; transplacental carcinogenesis and mutations in oncogenes and tumor suppressor genes in tumors of mice; and genotoxicity and clastogenicity following perinatal exposure of HIV-infected mothers and their uninfected infants. Collectively, the results obtained provide convincing biological plausibility for the postulate that perinatal exposure to nucleoside analogs puts children at elevated risk of developing cancers later in life. They further emphasize the importance of continued surveillance of these children for increased cancer risk and indicate a need for efforts to develop less genotoxic alternative agents.