Antiretroviral Prophylaxis and the Risk of Cleft Lip and Palate: Preliminary Signal Detection in the Food and Drug Administration's Adverse Events Reporting System Database

OBJECTIVE: Antiretroviral prophylaxis has been found to be effective in preventing vertical HIV transmission to the offspring of infected mothers. Because medicine and the art of public health require benefits to outweigh any plausible risks, our study aimed to explore and quantify preliminary associations between antiretroviral medications and clefting. METHODS: We analyzed 5 years of available data from the Food and Drug Administration's Adverse Events Reporting System (Medwatch program) and calculated reporting odds ratios (RORs) and their associated 95% confidence intervals (CIs). RESULTS: The medications with the highest effects were efavirenz with an ROR of 196 (95% CI, 86 to 447), lamivudine with an ROR of 60.2 (95% CI, 14.25 to 148), the combination abacavir sulfate/lamivudine/zidovudine with an ROR of 59.3, and nelfinavir with and ROR of 50.5, followed by nevirapine, lopinavir/ritonavir, and lamivudine/zidovudine. CONCLUSION: Given the multifactorial etiology of cleft lip and palate, further studies are needed to assess the relative safety of antiretroviral prophylaxis and the specific conditions or potential synergies that might lead to the development of this defect.