Plasma viremia in macaques infected with simian immunodeficiency virus: plasma viral load early in infection predicts survival

Abstract

A reliable method for the quantitation of plasma viremia in nonhuman primates infected with simian immunodeficiency virus (SIV) and related viruses is described. This method is based on an established quantitative-competitive PCR format and includes a truncated control for internal assay calibration. Optimization of assay conditions has significantly improved amplification specificity, and interassay variability is comparable to that of commercially available assays for human immunodeficiency virus (HIV) quantitation. This procedure was used to monitor viral loads in a group of Macaca mulatta animals that were infected with SIVsmE660 for over 2 years. Highly diverse profiles of plasma viremia were observed among animals, and high viral loads were associated with more rapid disease progression. Spearman rank correlation analyses were done for survival versus three parameters of viral load: plasma viremia, p27 core antigen, and frequency of infected peripheral blood mononuclear cells. Plasma viremia had the strongest overall correlation and was significantly (P < 0.05 to P < 0.01) associated with survival at 10 of the 13 time points examined. Plasma viremia did not correlate with survival during the primary viremia phase; however, the strength of this correlation increased with time postinfection and, remarkably, viremia levels as early as week 6 postinfection were highly predictive (P < 0.01) of relative survival. These findings are consistent with the available clinical data concerning viral load correlates early in HIV infection, and they provide further support for the view that disease outcome in lentiviral infection may be largely determined by events that occur shortly after infection.

On the analysis of viral load endpoints in HIV vaccine trials

“…In particular, baseline viral load shortly after acute infection (or 'viral load set point') has been shown to be highly prognostic for progression to AIDS [18][19][20] and is generally considered one of the best markers for disease progression in HIV seroconverters [21,22]. Similar results have been obtained in macaque challenge studies [23,24]; moreover, experimental interventions that reduced set point have been shown to delay disease progression [9,10,25]. Viral load has also been shown to be highly predictive of infectiousness [26] such that a vaccine's e ect on early viral load may also be a reasonable surrogate of VE I .…”

Analysis of the spleen proteome of chickens infected with reticuloendotheliosis virus

“…''upregulated protein; ''N'', no difference; ''*'', failed identification Analysis of the virus load revealed high levels of viral RNA copies in spleen tissue at 7, 14, and 21 dpi, indicating the development of persistent infection. The virus load reflects the status of viral replication and disease evolution, and it has therefore been used as an important marker for disease progression of retroviral infections [57,74]. Thus, it is conceivable that the virus copy numbers observed in the present study would be indicative of a high level of infection.…”

Dissecting the role of dendritic cells in simian immunodeficiency virus infection and AIDS

“…Nonhuman primate models are invaluable for advancing our understanding of virus-host interactions and disease pathogenesis, and none has been more informative in this regard than the simian immunodeficiency virus (SIV) model of human immunodeficiency virus (HIV) infection. Experimental SIV infection of rhesus macaques and other Asian nonhuman primate species results in progressive disease similar to HIV infection in humans, although with an accelerated course of decline; SIV infection of rhesus macaques is therefore a key model to study AIDS pathogenesis [1][2][3][4][5]. In contrast, SIV infection in "natural" African nonhuman primate hosts of SIV, such as the African green monkey and sooty mangabey, is nonpathogenic, and disease does not generally develop despite productive virus replication.…”