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Suppression of plasma viral load below 20 copies/ml is required to achieve a long‐term response to therapy

Raboud, Janet M.1; Montaner, Julio S.G.1,8; Conway, Brian1; Rae, Sandra1; Reiss, Peter2; Vella, Stephano3; Cooper, David4; Lange, Joep5; Harris, Marianne1; Wainberg, Mark A.6; Robinson, Patrick7; Myers, Maureen7; Hall, David7


Background: Current guidelines state that the goal of antiretroviral therapy for HIV-infected individuals is to suppress plasma viral load (pVL) to below 400 copies/ml

Methods: Predictors of achieving and maintaining pVL suppression were examined in a randomized trial of combinations of zidovudine, nevirapine and didanosine in patients with CD4+ T cell counts of between 200 and 600 × 106 cells/I who were naive to antiretroviral therapy and AIDS-free at enrolment.

Results: One hundred and four patients had pVL > 500 copies/ml at baseline and a pVL nadir below 500 copies/ml. Of these, 77 patients experienced an increase in pVL above 500 copies/ml. The median number of days of pVL suppression to below 500 copies/ml was 285 (42) for patients with pVL nadir ≤ (>) 20 copies/ml (P = 00.0001). The relative risk of an increase in pVL above 500 copies/ml associated with a pVL nadir below 20 copies/ml was 0.11 (P = 0.0001). The relative risks of an increase in pVL above 5000 copies/ml associated with a pVL nadir below 20 copies/ml or between 20 and 400 copies/ml were 0.05 [95% confidence interval (CI), 0.02–0.12] and 0.37 (95% CI, 0.23–0.61) respectively, compared with individuals with a pVL nadir > 400 copies/ml. Individuals with a pVL nadir ≤ 20 copies/ml were at a significantly lower risk of virologic failure than individuals with a pVL nadir of between 21 and 400 copies/ml (P = 0.0001).

Conclusions: Our results demonstrate that suppression of pVL below 20 copies/ml is necessary to achieve a long-term antiretroviral response. Our data support the need for a revision of current therapeutic guidelines for the management of HIV infection.

1Canadian HIV Trials Network and Centre for Excellence in HIV/AIDS, St Paul's Hospital/University of British Columbia, Vancouver, Canada

2Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, Amsterdam, The Netherlands

3Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy

4National Centre in HIV Epidemiology and Clinical Research, St. Vincent's Hospital Medical Centre, Darlinghurst, Sydney, Australia

5Department of Internal Medicine and Human Retrovirus Laboratory, Academic Medical Centre, Amsterdam, The Netherlands

6McGill University AIDS Centre, Jewish General Hospital, Montreal, Canada

7Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA.

8Requests for reprints to: J.S.G. Montaner, St. Paul's Hospital/University of British Columbia, 667–1081 Burrard St., Vancouver, Canada, V6Z 1Y6.

Note: This paper was presented at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, September, 1997 in Toronto, Ontario, Canada and at the 6th European Conference on Clinical Aspects and Treatment of HIV Infection, October 1997, Hamburg, Germany.

Sponsorship: this project was funded partially by the Canadian HIV Trials Network and Boehringer Ingelheim Pharmaceuticals Inc.

Date of receipt: 7 April 1998; revised: 27 May 1998; accepted 3 June 1998

© 1998 Lippincott Williams & Wilkins, Inc.