Increasing viral burden in CD4+ T cells from patients with human immunodeficiency virus (HIV) infection reflects rapidly progressive immunosuppression and clinical disease

Abstract

Objective: To determine over time the relation between viral burden and immunologic decline in patients with asymptomatic human immunodeficiency virus (HIV) infection.

Design: Blind analysis of cell samples from matched cohorts for HIV proviral DNA by polymerase chain reaction, retrospective analysis of clinical data on patients, and prospective follow-up of patients seropositive for the human immunodeficiency virus type 1 (HIV-1).

Setting: National research clinic and academic medical centers.

Patients: Cohort 1 included 12 healthy HIV-1-seropositive patients (average follow-up, 14 months): Six patients had stable disease and 6 developed rapidly progressive disease. Cohort 2 included 15 healthy HIV-1-seropositive patients from the Multi-center AIDS Cohort Study (average follow-up, 32 months): Eight patients had stable disease and 7 developed rapidly progressive disease. LABORATORY STUDIES: Quantitative polymerase chain reaction was done to determine the HIV-1 viral burden in sort-purified CD4+ T cells obtained from patients at various timepoints.

Measurements and main results: In patients who remained asymptomatic, frequencies of HIV-infected CD4+ T cells were low (less than 1/10,000 to 1/1000) at study entry and increased only minimally (none higher than 1/1000). In contrast, among patients who developed HIV-related symptoms including the acquired immunodeficiency syndrome (AIDS) despite having similar CD4 counts, frequencies of HIV-infected CD4+ T cells were higher at entry (greater than 1/1000) and increased substantially (greater than 1/100) in most within 3 months of developing progressive disease. This increase in HIV burden coincided with a significant decline over time in the percent of T4 cells (31% to 16%), whereas the percent of T4 cells was unchanged in persons who remained asymptomatic (33% to 34%).

Conclusions: Increasing viral burden in peripheral blood CD4+ T-cells is directly associated with a progressive decline in CD4+ T cells and deteriorating clinical course in HIV-infected patients.