Animal Models of Anti-HIV Drugs Exposure During Pregnancy: Effects on Neurobehavioral Development

In the last 10 years, zidovudine (AZT) has become the main prophylactic therapy against vertical HIV-1 transmission. AIDS Clinical Trials Group (ACTG) 076 have demonstrated that the administration of AZT to HIV-infected women during their third trimester of pregnancy, trough labor and given orally to babies for 6 weeks, reduced by two-thirds the rate of vertical infection. Although the rapid diffusion of this regimen into clinical practice together with the implementation of HIV counseling and testing practices have dramatically reduced the vertical transmission rate in the US and Western Europe, there is a growing concern on the adverse effects of antiretroviral therapy on the fetus and the newborn. In fact, even though shorter regimen therapies that are less complex and expensive to implement in poor countries have been demonstrated as effective as ACTG 076 regimen, the distribution of the risk of vertical transmission in the developing countries is still very high. Consequently, a large number of unborns will be a candidate to developmental exposure to antiretroviral agents. To date, data on the transplacental mutagenicity, carcinogenicity and mitochondrial dysfunction induced by developmental exposure to AZT have been reported in several animal models. Furthermore, one study reported severe yet few human cases of cardiomyopathy and neurological disease likely associated with mitochondrial dysfunction in uninfected infants of seropositive mothers perinatally exposed to AZT. For all of these reasons, many investigations have been focusing on the assessment of the potential adverse effects of nucleoside reverse transcriptase (RT) inhibitors (NRTI) administration during development. A survey of the main results derived from clinical and animal studies is reported here, focusing on those neurobehavioral studies that have been looking for specific and/or aspecific changes in the nervous system induced by NRTI exposure in utero.