ESTIMATES OF THE VIROLOGICAL BENEFIT OF ANTIRETROVIRAL THERAPY ARE BOTH ASSAY-DEPENDENT AND ANALYSIS-DEPENDENT

Objective: To assess the potential discrepancies in reported changes i n plasma viral load (PVL) depending on how values below the detection limit of the assay are handled in the data analysis phase of a randomi zed controlled clinical trial. Design: Data from a recently completed clinical trial comparing combinations of zidovudine, didanosine and ne virapine were analysed. In this trial, PVL was measured using an assay with a lower quantification limit of 400 HIV-1 RNA copies/ml initiall y. All PVL values less than 500 copies/ml were retested with a more se nsitive assay with a lower quantification limit of 20 copies/ml. Metho ds: Several summary measures for assessing change in PVL were calculat ed using three different methods to adjust for PVL values less than th e quantification limit of the assay. The differences between these mea sures were evaluated. Results: We found that the magnitude of the disc repancy between summary measures used to report changes in PVL depende d on the proportion of subjects with PVL less than the quantification limit of the assay, how those observations were handled in the data an alysis, and the relative difference between the quantification limits of the conventional and more sensitive assay. Conclusion: The lack of consensus in reporting of PVL data in the literature makes the interpr etation of published trial results difficult In the absence of agreeme nt on the most appropriate summary measure of PVL data, we recommend t hat all summaries include information on the quantification limit of t he assay used, the proportion of observations at or below the quantifi cation limit and how these observations were handled in the data analy sis. (C) 1998 Lippincott Williams & Wilkins