Rapid viral decay in simian immunodeficiency virus-infected macaques receiving quadruple antiretroviral therapy

Abstract

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.

FIG. 1.

Dynamics of plasma SIV RNA levels in four (E1, E2, E5, and E6) SIV-infected monkeys who where given antiretroviral therapy on days 0 to 7. The results from the piecewise linear regression analysis are shown as a blue dashed line for each phase (days 1 to 4, days 4 to 7, and days 7 to 14). The results from the nonlinear model are shown as a red solid line. Note that the pretreatment plasma virus level in monkey E6 exceeded the upper quantification limit of the assay, i.e., 680,000 SIV RNA copies/ml.