Post-exposure chemoprophylaxis (PECP) against SIV infection of macaques asa model for protection from HIV infection

We report that simian immunodeficiency virus (SIV) infection in macaques is a valuable animal model for studying post-exposure chemoprophylaxis (PECP) . PECP with the acyclic nucleoside reverse transcriptase inhibitors 9-(2-ph osphonylmetho-xyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)a denine (PMPA) at early viral infection can provide long-term protection aga inst subsequent heterologous SIV challenge. Eight macaques previously treat ed with PECP (called PECP macaques) and four naive controls were challenged intravenously with the most virulent form of SIV, SIVPBj14. All controls s howed signs of SIVPBj14-induced acute disease syndrome on days 6 and 7 post -inoculation (PI). One had a fatal viral infection and two surviving contro ls had persistent infection and decreased CD4+ cell count. Virologic studie s of the three surviving controls revealed SIV in multiple lymphoid tissues and peripheral blood mononuclear cells (PBMCs) at necropsy. In contrast, t he PECP macaques showed none to mild signs of acute disease syndrome at day 9 PI and exhibited only transient SIV infection in PBMCs between weeks 1 a nd 8 PI. In virologic studies of five PECP macaques necropsied, two macaque s were SIV-negative and the other three were SIV-positive only in either ly mph node or bone marrow. Three SIVPBj14-challenged PECP macaques, that were randomly reserved for a follow-up study for > 4.0 years PI showed extremel y low to undetectable levels of PBMC-associated viremia and normal to incre ased levels of CD4 + and CD8 + cell counts throughout the study. Our result s indicate that early PECP could activate immune responses to protect again st subsequent infection with heterologous challenge virus.