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Journal of Virology, October 2006, p. 9861-9864, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00394-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Rapid Viral Decay in Simian Immunodeficiency Virus-Infected Macaques Receiving Quadruple Antiretroviral Therapy

Eleonor Brandin,1,2 Rigmor Thorstensson,1 Sebastian Bonhoeffer,3 and Jan Albert1,2*

Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden,1 Microbiology and Tumorbiology Center, Karolinska Institutet, SE-171 77 Stockholm, Sweden,2 Institute of Integrative Biology, ETH Zürich, CH-8092 Zürich, Switzerland3

Received 24 February 2006/ Accepted 14 June 2006

The viral dynamics in human immunodeficiency virus type 1 (HIV-1) infection have been studied extensively using mathematical modeling, but data from other primate lentivirus systems are scarce. This study was initiated to increase the understanding of the differences and similarities between the different primate lentiviruses. Four cynomolgus macaques were infected with SIVmac251. Six months after infection the monkeys received a 7-day course of subcutaneous, quadruple antiretroviral therapy with zidovudine, lamivudine, tenofovir, and ritonavir-boosted lopinavir. Plasma virus levels were determined before therapy, daily during the first 10 days of therapy, and after 14 days using a sensitive commercial reverse transcriptase assay. All four monkeys showed a rapid and uniform decline in plasma virus load between day 1 and day 4 of treatment (first-phase decay). Two mathematical models, a piecewise linear regression analysis and a nonlinear model, were used to estimate the rate of viral decay in plasma and gave similar results. The mean half-life for plasma virus was 0.47 days (range, 0.37 to 0.50) and reflects the underlying decline of virus-producing CD4+ lymphocytes. This is the fastest primate lentivirus decay described hitherto. The rapid decay may be due to the high antiviral potency of the therapy or to intrinsic differences between simian immunodeficiency virus (SIV) infection in macaques and HIV-1 infection in humans.

* Corresponding author. Mailing address: Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden. Phone: 46 8 457 2605. Fax: 46 8 33 72 72. E-mail: Jan.Albert{at}smi.ki.se.

Journal of Virology, October 2006, p. 9861-9864, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00394-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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