SEQUENTIAL DETERMINATION OF VIRAL LOAD AND PHENOTYPE IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

Detailed studies of HIV viral load and phenotype were performed on seq uentially cryopreserved peripheral blood mononuclear cells (PBMCs) fro m eight infected individuals followed in the Eos Angeles Multicenter A IDS Cohort Study. Three individuals remained clinically and immunologi cally stable over a 5- to 8-year period, three demonstrated precipitou s and two gradual declines in CD4(+) T lymphocytes. Viral load in PBMC s was quantitated by limiting dilution culture and DNA PCR, while mini mally passaged viral isolates were studied for their ability to induce syncytium formation in vitro and, when relevant, sensitivity to zidov udine (ZDV). Viral burden remained relatively low in those who remaine d clinically and immunologically stable, while increasing substantiall y in all five individuals who experienced a decline in CD4(+) T lympho cytes. Two subjects were noted to have a switch from non-syncytium-ind ucing (NSI) to syncytium-inducing (SI) isolates immediately preceding a precipitous decline in CD4(+) T lymphocytes, while the third individ ual who experienced such a decline and the two who had gradual decline s did not develop SI isolates. Moreover, of the three subjects who exp erienced a decrease in CD4(+) T lymphocyte number and were given ZDV d uring the study period, none were noted to develop resistance to this agent. In summary, the virology in clinically and immunologically stab le individuals was characterized by relatively low viral burden in PBM Cs and a predominance of NSI isolates. In contrast, while there was co nsistently an inverse relationship between viral load and CD4(+) T lym phocyte number in those who experienced an immunological decline, a ph enotypic switch from NSI to SI isolates occurred in only two of the fi ve subjects who demonstrated such a decline, and no ZDV-resistant isol ates were detected in any of the treated individuals.