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Viral Replication Under Combination Antiretroviral Therapy: A Comparison of Four Different Regimens

Ghani Azra C.; Ferguson, Neil M.; Fraser, Christophe; Donnelly, Christl A.; Danner, Sven; Reiss, Peter; Lange, Joep; Goudsmit, Jaap; Anderson, Roy M.; De Wolf, Frank
JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2002
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A mathematical model of the interaction among CD4+ T-cells, HIV-1, and antiretroviral drugs was fitted to the viral load decline following initiation of combination therapy to estimate differences in the residual reproductive capacity of virus (R0) in the average patient in each group. Four regimens were studied: 12 patients on 5-drug nucleoside reverse transcriptase inhibitor (NRTIs), nonnucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitor (PI)-containing combination therapy, 11 patients on PI-containing triple therapy, 10 patients on double NRTI therapy, and 10 patients on NNRTI-containing triple therapy. Model fits were used to estimate R0. The NNRTI-containing triple therapy and the 5-drug regimen blocked viral replication to the greatest extent (R0 = 0.85; 95% confidence interval [CI], 0.79-0.91; and 0.90, 95% CI, 0.82-0.98, respectively), with the former being significantly better than the PI-containing triple regimen (R0 = 0.98; 95% CI, 0.92-1.03; p = .007). Both the NNRTI-containing and the 5-drug regimen, as well as the PIcontaining triple therapy, were significantly better at blocking viral replication than the double NRTI therapy (R0 = 1.04; 95% CI, 1.0-1.07). Measurement of viral load after approximately 7 days provided the most accurate measure of the degree of viral suppression induced by a given drug regimen.

S. Danner is currently affiliated with the Department of Internal Medicine, Faculty of Medicine of the Free University, Amsterdam, The Netherlands.

Address correspondence and reprint requests to A. Ghani, Department of Infectious Disease Epidemiology, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 1PG U.K.; e-mail:

Manuscript received June 26, 2001; accepted March 6, 2002.

© 2002 Lippincott Williams & Wilkins, Inc.