Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus.

Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in SHIV(DH12)-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previously reported that the administration of anti-human CD8 mAb to rhesus macaques at the time of primary SHIV(DH12) infection resulted in marked elevations of virus loads. One of the treated animals experienced rapid and profound depletions of circulating CD4(+) T lymphocytes. Although the CD4(+) T cell number partially recovered, this monkey subsequently suffered significant weight loss and was euthanized. A tissue culture virus stock derived from this animal, designated SHIV(DH12R), induced marked and rapid CD4(+) cell loss after i.v. inoculation of rhesus monkeys. Retrospective analyses of clinical specimens, collected during the emergence of SHIV(DH12R) indicated: (i) the input cloned SHIV remained the predominant virus during the first 5-7 months of infection; (ii) variants bearing only a few of the SHIV(DH12R) consensus changes first appeared 7 months after the administration of anti-CD8 mAb; (iii) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (iv) no neutralizing antibody against SHIV(DH12R) ever developed.