IMMUNE STIMULATION MAY CONTRIBUTE TO ENHANCED PROGRESSION OF SIV INDUCED DISEASE IN RHESUS MACAQUES

A number of rhesus macaques experimentally infected with SIV isolates such as SIVmac251, fail to seroconvert, develop high plasma viremia an d die rapidly (within 6-7 months p.i.). We hypothesized that such rapi d progression is a result of a state of hyperimmune activation and con comitant immune suppression of these animals at the time of virus chal lenge. In efforts to test the hypothesis that immune activation leads to rapid progression of lentivirus-induced disease, adult rhesus macaq ues were infected with SIVmac251 and received an alternate monthly sch edule of repeated immunization with allogeneic cells, keyhole limpet h emocyanin and tetanus toroid (group I). For purposes of controls, a gr oup of monkeys was infected with the same pool and dose of virus but w ere not immunized (group II) and a group was immunized with the same s chedule 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 seroco nvert or developed very low levels of SIV antibodies, had high plasma p27 defined antigenemia, and died within 8 months (2/3 died within 4 m onths). Of the animals in group LI (n=8), two patterns emerged as we h ad noted before. One subgroup (3 animals), displayed the same profile as group I (failure to fully seroconvert, high p27 levels and death by 8 months), whereas the other subgroup (5 animals) seroconverted, had low plasma p27 levels, and survived past II months (2/5 still alive pa st 22 months). All 3 animals in group III remained healthy. The data p rovided herein suggest that either experimental or natural (due to fac tors not clear at present) immune stimulation may lead to accelerated lentivirus induced disease progression most likely due to immune suppr ession and has implications for the understanding of the mechanisms fo r the rate of disease progression in human HIV-1 infection.