Incidence of cancer in children perinatally exposed to nucleoside reverse transcriptase inhibitors

Abstract

Context: Long-term studies of tolerance to perinatal exposure to antiretroviral nucleoside reverse transcriptase inhibitors are required, in view of the potential genotoxicity of some of these molecules.

Objective: To evaluate the incidence of cancers in uninfected children born to HIV-infected mothers.

Method: Cancers were detected in a nationwide prospective cohort of children born to HIV-infected mothers by standardized questionnaire during the prospective follow-up period of 2 years; thereafter, they were detected by spontaneous pharmacovigilance declaration and by crosschecking data with the national registries of childhood cancer. Standardized incidence ratio for incidence comparisons with general population.

Results: Ten cases of cancer were detected among the 9127 exposed HIV-uninfected children (median age: 5.4 years, 53 052 person-years of follow-up). The overall incidence did not differ significantly from that expected for the general population: 10 cases observed versus 8.9 and 9.6 expected depending on whether 1990-1999 or 2000-2004 national rates were used as reference [standardized incidence ratio of 1.1 (0.3-1.5) and 1.0 (0.5-1.9)]. Five cases of central nervous system cancer were observed (standardized incidence ratio of 3.1 [1.0-7.2] P = 0.05 and 2.4 [0.8-5.6], P = 0.12). The relative risk of cancer for children exposed to didanosine-lamivudine combination was higher than that for zidovudine monotherapy [hazard ratio: 13.6 (2.5-73.9)].

Conclusion: This study did not evidence an overall increase in cancer risk in nucleoside reverse transcriptase inhibitor exposed children until 5 years of age. Results suggesting associations with specific nucleoside reverse transcriptase inhibitor combinations need further investigations. A longer surveillance, including differential analysis of the different cancer sites and various nucleoside reverse transcriptase inhibitors administered is warranted.