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

Cohen, Calvin J.a; Hunt, Susanb; Sension, Michaelc; Farthing, Charlesd; Conant, Marcuse; Jacobson, Susanf; Nadler, Jeffreyg; Verbiest, Wernerh; Hertogs, Kurth; Ames, Michaeli; Rinehart, Alex R.j; Graham, Neil M.*; and the VIRA3001 Study Team

Clinical

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.

From the aCommunity Research Initiative of New England, Boston, MA 02215, USA; bUniversity of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA; cNorth Broward Hospital District, Fort Lauderdale, FL 33312, USA; dAIDS Healthcare Foundation, Los Angeles, CA 90027-6069, USA; eDermatology/HIV Consultations, San Francisco, CA 94117, USA; fEast Bay AIDS Center, Clinical Faculty, Department of Family and Community Medicine, Berkeley, CA 94705, USA; gUniversity of South Florida, Tampa, FL 33602, USA; hTibotec Virco NV, B-2800 Mechelen, Belgium; iGlaxoSmithKline, Research Triangle Park, NC 27709, USA; and jTibotec Virco USA, Durham, NC 27713, USA, formally at Glaxo Wellcome, Inc.

*For members of the VIRA3001 Study Team see Appendix.

The results of this study were presented in part in abstract 237 at the 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, USA, 30 January–2 February 2000.

Correspondence to: Neil Graham, MD, Vice President, Medical Department, Tibotec-Virco USA, 2505 Meridian Parkway, Suite 350, Durham, NC 27713, USA. Tel: +1 919 361 9010 (Ext 3245); fax: +1 919 361 9020; e-mail: neil.graham@tibotec-virco.com

Received: 23 March 2001;

revised: 1 October 2001; accepted: 3 October 2001.

Sponsorship: Provided by Glaxo Wellcome, Inc. (primary) and Virco NV.

© 2002 Lippincott Williams & Wilkins, Inc.