Sequential Determination of Viral Load and Phenotype in Human Immunodeficiency Virus Type 1 Infection

Abstract

Detailed studies of HIV viral load and phenotype were performed on sequentially cryopreserved peripheral blood mononuclear cells (PBMCs) from eight infected individuals followed in the Los Angeles Multicenter AIDS Cohort Study. Three individuals remained clinically and immunologically stable over a 5- to 8-year period, three demonstrated precipitous and two gradual declines in CD4⁺ T lymphocytes. Viral load in PBMCs was quantitated by limiting dilution culture and DNA PCR, while minimally passaged viral isolates were studied for their ability to induce syncytium formation in vitro and, when relevant, sensitivity to zidovudine (ZDV). Viral burden remained relatively low in those who remained clinically and immunologically stable, while increasing substantially in all five individuals who experienced a decline in CD4⁺ T lymphocytes. Two subjects were noted to have a switch from non-syncytium-inducing (NSI) to syncytium-inducing (SI) isolates immediately preceding a precipitous decline in CD4⁺ T lymphocytes, while the third individual who experienced such a decline and the two who had gradual declines did not develop SI isolates. Moreover, of the three subjects who experienced a decrease in CD4⁺ T lymphocyte number and were given ZDV during the study period, none were noted to develop resistance to this agent. In summary, the virology in clinically and immunologically stable individuals was characterized by relatively low viral burden in PBMCs and a predominance of NSI isolates. In contrast, while there was consistently an inverse relationship between viral load and CD4⁺ T lymphocyte number in those who experienced an immunological decline, a phenotypic switch from NSI to SI isolates occurred in only two of the five subjects who demonstrated such a decline, and no ZDV-resistant isolates were detected in any of the treated individuals.