A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy

Calvin J. Cohen, Susan Hunt, Michael Sension, Charles Farthing, Marcus Conant, Susan Jacobson, Jeffrey Nadler, Werner Verbiest, Kurt Hertogs, Michael Ames, Alex R. Rinehart, Neil M. Graham, Roberto Arduino, Carol Brosgart, Stephen Brown, Ann Collier, Steven Davis, Jeffrey Galpin, Jeffrey Goodgame, Howard GrossmanW. Keith Henry, Harold Kessler, Martin Markowitz, Douglas Mayers, Michael Saag, Shannon Schrader, Allan Stein, Richard Stryker, Melanie Thompson, Gabriel Torres, Deborah Copeland

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

Objective: To compare the effect of treatment decisions guided by phenotypic resistance testing (PRT) or standard of care (SOC) on short-term virological response. Design: A prospective, randomized, controlled clinical trial conducted in 25 university and private practice centers in the United States. Participants: A total of 272 subjects who failed to achieve or maintain virological suppression (HIV-1-RNA plasma level > 2000 copies/ml) with previous exposure to two or more nucleoside reverse transcriptase inhibitors and one protease inhibitor. Interventions: Randomization was to antiretroviral therapy guided by PRT or SOC. Main outcome measures: The percentage of subjects with HIV-1-RNA plasma levels less than 400 copies/ml at week 16 (primary); change from baseline in HIV-1-RNA plasma levels and number of 'active' (less than fourfold resistance) antiretroviral agents used (secondary). Results: At week 16, using intent-to-treat (ITT) analysis, a greater proportion of subjects had HIV-1-RNA levels less than 400 copies/ml in the PRT than in the SOC arm (P = 0.036, ITT observed; P = 0.079, ITT missing equals failure). An ITT observed analysis showed that subjects in the PRT arm had a significantly greater median reduction in HIV-1-RNA levels from baseline than the SOC arm (P= 0.005 for 400 copies/ml; P= 0.049 for 50 copies/ml assay detection limit). Significantly more subjects in the PRT arm were treated with two or more 'active' antiretroviral agents than in the SOC arm (P = 0.003). Conclusion: Antiretroviral treatment guided prospectively by PRT led to the increased use of 'active' antiretroviral agents and was associated with a significantly better virological response.

Original languageEnglish (US)
Pages (from-to)579-588
Number of pages10
JournalAIDS
Volume16
Issue number4
DOIs
StatePublished - Mar 8 2002

Keywords

  • Clinical trials
  • HIV diagnostic tests
  • HIV drug resistance/resistance mutations
  • Highly active antiretroviral therapy
  • Phenotypic resistance testing

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    Cohen, C. J., Hunt, S., Sension, M., Farthing, C., Conant, M., Jacobson, S., Nadler, J., Verbiest, W., Hertogs, K., Ames, M., Rinehart, A. R., Graham, N. M., Arduino, R., Brosgart, C., Brown, S., Collier, A., Davis, S., Galpin, J., Goodgame, J., ... Copeland, D. (2002). A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy. AIDS, 16(4), 579-588. https://doi.org/10.1097/00002030-200203080-00009