The draft guidance, called the "Guidance on Antiviral Product Development — Conducting and Submitting Virology Studies to the Agency," encourages sponsors to use the following sample format for submitting HIV-1 resistance data: One dataset combining patient data, endpoint data, genotypic data, and phenotypic data.
Other subdivisions of data can be based on clinical study, baseline isolates, or virologic failure isolates, though the subdivisions should be discussed with the Division of Antiviral Products (DAVP) before submission.
The guidance focuses on seven key areas:
VI. Co-Receptor Usage;
V. Protease Cleavage Sites;
IV. Phenotypic Data;
III. Genotypic Data;
II. Endpoint Data; and
I. Patient Data.
“To identify any potential formatting problems as early as possible, all sponsors are encouraged to submit preliminary (or mock) resistance datasets to the DAVP before assembling formal clinical trial resistance datasets,” the agency says.
Genotypic data should be provided on the corresponding record for each patient isolate for baseline isolates of all patients in treatment-experienced studies, and the endpoint isolates of patients who are classified as virologic failures and discontinuations in all studies. In treatment-naïve studies, a baseline sample should be collected and stored from all patients for future phenotypic and genotypic analysis of virologic failures.
Genotypic data also should be provided for the HIV-1 target, one amino acid per column, with the wild-type (WT) amino acid in the column heading. Changes from WT standard sequence should be indicated in the row.
Sponsors collecting and submitting next generation sequencing (NGS) data should consult with DAVP early in the experimental design process, as additional guidance will be necessary. To initiate discussions with DAVP, sponsors should provide the details of their planned NGS
This guidance is being revised to provide the current format, recommended definitions, standardization of column headings and variables, and recommended data for submission of HIV resistance datasets. To initiate discussions with DAVP, sponsors should provide the details of their planned NGS analyses, including the performance characteristics of the assay and bioinformatics software to be used for analysis.