PATTERNS OF VIRAL REPLICATION CORRELATE WITH OUTCOME IN SIMIAN IMMUNODEFICIENCY VIRUS (SIV)-INFECTED MACAQUES - EFFECT OF PRIOR IMMUNIZATION WITH A TRIVALENT SIV VACCINE IN MODIFIED VACCINIA VIRUS ANKARA

The dynamics of plasma viremia were explored in a group of 12 simian i mmunodeficiency virus (SIV)infected rhesus macaques (Macaca mulatta) t hat had received prior immunization with either nonrecombinant or triv alent (gag-pol, env) SIV-recombinant vaccinia viruses. Three distinct patterns of viral replication observed during and following primary vi remia accounted for significant differences in survival times. High-le vel primary plasma viremia with subsequently increasing viremia was as sociated with rapid progression to AIDS (n = 2). A high-level primary plasma virus load with a transient decline and subsequent progressive increase in viremia in the post-acute phase of infection was associate d with progression to AIDS within a year (n = 6). Low levels of primar y plasma viremia followed by sustained restriction of virus replicatio n were associated with maintenance of normal lymphocyte subsets and in tact lymphoid architecture (n = 4), reminiscent of the profile observe d in human immunodeficiency virus type 1-infected long-term nonprogres sors. Three of four macaques that showed this pattern had been immuniz ed with an SIV recombinant derived from the attenuated vaccinia virus, modified vaccinia virus Ankara. These data link the dynamics and exte nt of virus replication to disease course and suggest that sustained s uppression of virus promotes long-term, asymptomatic survival of SIV-i nfected macaques. These findings also suggest that vaccine modulation of host immunity may have profound beneficial effects on the subsequen t disease course, even if sterilizing immunity is not achieved.