CD3(-T-CELL AND CD20(+)-B-CELL CHANGES PREDICT RAPID DISEASE PROGRESSION AFTER SIMIAN-HUMAN IMMUNODEFICIENCY VIRUS-INFECTION IN MACAQUES())

Simian-human immunodeficiency virus 89.6PD (SHIV89.6PD) was pathogenic after intrarectal inoculation of rhesus macaques. Infection was achie ved with a minimum of 2,500 tissue culture infectious doses of cell-fi ee virus stock and there was no evidence for transient viremia in ani mals receiving subinfectious doses by the intrarectal route, Some anim als experienced rapid progression of disease characterized by loss of greater than 90% of circulating CD4(+) T cells, sustained decreases in CD20(+) B cells, failure to elicit, virus-binding antibodies in plasm a, and high levels of antigenemia. Slower-progressing animals had mode rate but varying losses of CD4(+) T cells; showed increases in circula ting CD20(+) B cells; mounted rigorous responses to antibodies in plas ma, including neutralizing antibodies; and had low or undetectable lev els of antigenemia. Rapid progression led to death within 30 weeks aft er intrarectal inoculation, Plasma antigenemia at 2 weeks after inocul ation (P less than or equal to 0.002), B- and T-cell losses (P less th an or equal to 0.013), and failure to seroconvert (P less than or equa l to 0.005) were correlated statistically with rapid progression. Corr elations were evident by 2 to 4 weeks after intrarectal SHIV inoculati on, indicating that early events in the host-pathogen interaction dete rmined the clinical outcome.