A variable number of rhesus macaques experimentally infected with certain SIV isolates such as SIVmac251, fail to seroconvert, develop high plasma viremia and die. This rapid progression is a result of a state of hyperimmune activation and concomitant immune suppression of these animals at the time of virus challenge. In efforts to test the hypothesis that immune activation leads to rapid progression of lentivirus-induced disease, adult rhesus macaques were infected with SIVmac251 and received an alternate monthly schedule of repeated immunization with allogeneic cells, keyhole limpet hemocyanin and tetanus toxoid (group I). For purposes of controls, a group of monkeys was infected with the same pool and dose of virus but were not immunized (group II) and a group was immunized with the same schedule of multiple antigens as group I but were not infected with SIV (group III). All the animals in group I (n=3) either failed to seroconvert or developed very low levels of SIV antibodies, had high plasma p27 defined antigenemia and died within eight months (two out of three died within four months). Of the animals in group II (n=8), two patterns emerged as we had noted before. One subgroup (three animals), displayed the same profile as group I (failure to fully seroconvert, high p27 levels and death by eight months) whereas the other subgroup (five animals) seroconverted, had low plasma p27 levels and survived past eleven months (two out of five are still alive past 18 months). All three animals in group III remain healthy to date. The data provided herein suggest that either experimental or natural (due to factors not clear at present) immune stimulation many lead to accelerated lentivirus induced disease progression most likely due to immune suppression and has implications for the understanding of the mechanisms for the rate of disease progression in human HIV-1 infection.
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