Variability of Viral Load in Plasma of Rhesus Monkeys Inoculated with Simian Immunodeficiency Virus or Simian-Human Immunodeficiency Virus: Implications for Using Nonhuman Primate AIDS Models To Test Vaccines and Therapeutics

Abstract

Viral RNA level in plasma is a sensitive experimental endpoint for evaluating the efficacy of AIDS vaccines or therapies in nonhuman primates. By quantifying viral RNA in the plasma of 77 rhesus monkeys for 10 weeks after inoculation with simian-human immunodeficiency virus 89.6P (SHIV-89.6P) or simian immunodeficiency virus mac 251 (SIVmac 251), we estimated variability in three viral load (VL) measures: peak VL, the postacute set point VL, and VL decline from peak. Such estimates of biological variability are essential for determining the number of animals needed per group and may be helpful for selecting the most appropriate measure to use as the experimental endpoint. Peak VL was positively correlated with set point VL for both viruses. Variability (standard deviation) was substantially higher in monkeys infected with SIVmac 251 than in those infected with SHIV-89.6P for set point VL and VL decline. The variability of peak VL was less than one-half that of set point VL variability and only about two-thirds of that of VL decline, implying that the same treatment-related difference in peak VL could be detected with fewer animals than set point VL or VL decline. Thus, differences in VL variability over the course of infection and between viruses need to be considered when designing studies using the nonhuman primate AIDS models.

Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model

“…Consistent with previous results (35), the SIV-infected macaques developed peak viremia within the first 7 to 14 DPI-SIV and reached the viral set point by week 6 postinoculation (Fig. 3A).…”

Improved Vaccine Protection from Simian AIDS by the Addition of Nonstructural Simian Immunodeficiency Virus Genes

“…6A). This is in line with previous observations (66). It has recently been demonstrated that a massive initial infection of memory CD4 ϩ T cells results in a depletion of 30 -90% of these cells from the lymphoid tissues and mucosal surface during the first 2 wk of infection (1-3).…”

Estimating the Infectivity of CCR5-Tropic Simian Immunodeficiency Virus SIV mac251 in the Gut

“…3A). The average peak viral load for unvaccinated macaques infected with SIV mac251 is approximately 4.57 ϫ 10 7 copies ml Ϫ1 (22). In the absence of interventions, this results in almost complete depletion of CD4 ϩ memory T cells in the jejunum as observed experimentally and predicted by our fits (Fig.…”

“…However, the peak viral load in blood for CCR5-tropic SIV mac251 infections (4.57 ϫ 10 7 copies ml Ϫ1 ) is approximately 2.7 times lower than for CXCR4-tropic SHIV89.6P infection (mean of 1.22 ϫ 10 8 copies ml Ϫ1 ) (10,22). Although the infection rates differ considerably, surprisingly, we find that if we align the infection curves to account for the average peak viral load in control animals in the respective models, reducing the viral load is expected to have the same outcome, in terms of CD4 ϩ T-cell depletion, in SHIV89.6P as in SIV mac251 infection (Fig.…”