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

Viral RNA level in plasma is a sensitive experimental endpoint for evaluati ng the efficacy of AIDS vaccines or therapies in nonhuman primates. By quan tifying viral RNA in the plasma of 77 rhesus monkeys for 10 weeks after ino culation with simian-human immunodeficiency virus 89.6P (SHIV-89.6P) or sim ian immunodeficiency virus mac 251 (SIVmac 251), we estimated variability i n three viral load (VL) measures: peak VL, the postacute set point NIL, and NIL decline from peak. Such estimates of biological variability are essent ial for determining the number of animals needed per group and may be helpf ul for selecting the most appropriate measure to use as the experimental en dpoint. Peak VL was positively correlated with set point VL for both viruse s. Variability (standard deviation) was substantially higher in monkeys inf ected with SIVmac 251 than in those infected with SHIV-89.6P for set point VL and NIL decline. The variability of peak VL was less than one-half that of set point NIL variability and only about two-thirds of that of VL declin e, implying that the same treatment-related difference in peak VL could be detected with fewer animals than set point VL or VL decline. Thus, differen ces in VL variability over the course of infection and between viruses need to be considered when designing studies using the nonhuman primate AIDS mo dels.