The role of non-nucleoside reverse transcriptase inhibitors in children with HIV-1 infection

Over 1.4 million of the worlds' children are infected with HIV-1, mostly acquired in the perinatal period. Antiviral therapeutic options for children with HIV-1 infection have lagged behind those for infected adults. However, we now know that prevention of perinatal HIV-1 transmission to children is possible and that combination therapy for the management of infected children is efficacious. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are developing a more prominent role in combination therapy regimens, particularly as alternatives to protease inhibitors. They also have a role in preventing perinatal transmission, where it has been shown that only 2 doses of the NNRTI nevirapine can significantly reduce mother-to-child transmission of HIV-1. This has major therapeutic implications, particularly in areas where combination therapy is not readily available. Palatable paediatric formulations of NNRTIs are available or are being developed. Whilst pharmacokinetic data regarding the use of antiretrovirals in children remain scarce, published clinical trials have demonstrated the efficacy of NNRTIs when used as part of combination regimens in the management of HIV-1 infected children. The toxicity profile of NNRTIs is relatively favourable; however, severe skin rash, hepatotoxicity and central nervous system adverse effects with various NNRTIs can lead to treatment cessation. The development of class resistance with single step mutations in the reverse transcriptase gene remains a major therapeutic problem with this class of antiretrovirals. Novel NNRTIs under development are of interest either because of improved pharmacodynamics, reduced toxicity profiles or because of action against NNRTI-mutation containing resistant virus. There are no data available yet on the use of these drugs in the paediatric population.