This guidance provides recommendations for the development of antiretroviral drugs regulated within the Center for Drug Evaluation and Research at the Food and Drug Administration (FDA) for the treatment of human immunodeficiency virus-1 (HIV-1 or HIV) infection. Specifically, this guidance addresses the FDA’s current thinking regarding the overall development program and clinical trial designs for antiretroviral drugs to support an indication for the treatment of HIV-1 infection. This draft guidance is intended to serve as a focus for continued discussions among the Division of Antiviral Products (DAVP), pharmaceutical sponsors, the academic community, and the public. The organization of the guidance parallels the development plan for a particular drug or biologic.
This guidance revises the guidance for industry Antiretroviral Drugs Using Plasma HIV-RNA Measurements — Clinical Considerations for Accelerated and Traditional Approval issued in October 2002. After it has been finalized, this guidance will replace the October 2002 guidance. Significant changes from the 2002 version include: (1) more details on nonclinical development of antiretroviral drugs; (2) a greater emphasis on recommended trial designs for HIV-1-infected heavily treatment-experienced patients (those with multiple-drug resistant virus and few remaining therapeutic options); (3) use of a primary endpoint evaluating early virologic changes for studies in heavily treatment experienced patients; and (4) use of the traditional approval pathway for initial approval of all antiretrovirals with primary analysis time points dependent on the indication sought instead of an accelerated approval pathway followed by traditional approval. This guidance does not address the use of antiviral drugs for preventing the transmission of HIV-1 infection. Also, this guidance does not address the development of therapeutics, without antiviral mechanisms, intended to mitigate or reverse clinical or pathophysiological outcomes of immunologic suppression of HIV-1 infection. Additionally, this guidance does not contain discussion of the general issues of clinical trial design or statistical analyses for HIV antiretroviral trials. Those topics are addressed in the ICH guidances for industry E9 – Statistical Principles for Clinical Trials – and E10 – Choice of Control Group and Related Issues in Clinical Trials. This guidance also does not contain details regarding nonclinical safety and toxicology studies that should be conducted in standard animal models as described in the guidance for industry Nonclinical Safety Evaluation of Drug or Biologic Combinations.