Timing of carcinogenicity studies and predictability of genotoxicity for tumorigenicity in anti-HIV drug development.

The timing of carcinogenicity studies in parallel with the clinical development of anti-human immunodeficiency virus (HIV) drugs has been flexible for most cases in the past. This includes postponement of the initiation of the studies and submission of final audited reports to the US Food and Drug Administration (FDA) for a new drug application (NDA) approval. We address this regulatory practice for anti-HIV drugs for which, in the past, there had been no effective treatment. We also examine the correlation of genotoxicity data with carcinogenicity data for the varied subclasses of anti-HIV drugs. We suggest that this regulatory policy regarding the timing of carcinogenicity testing does not compromise the safety standards of FDA's drug evaluation and the approval process. The policy does facilitate availability of these agents to meet the medical needs of the target population. Our analysis on the profile of carcinogenicity findings of anti-HIV drugs shows trends of class effects. Additionally, both carcinogenicity and genotoxicity data show significant correlations, which provide useful insights into issues involving these 2 important areas of toxicological investigations.