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 Multicenter 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 (< 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 (> 1/1000) and increased substantially (> 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+ cells and deteriorating clinical course in HIV-infected patients.