Increasing Viral Burden in CD4+ T Cells from Patients with Human Immunodeficiency Virus (HIV) Infection Reflects Rapidly Progressive Immunosuppression and Clinical Disease

doi:10.1059/0003-4819-113-6-438

Increasing Viral Burden in CD4+ T Cells from Patients with Human Immunodeficiency Virus (HIV) Infection Reflects Rapidly Progressive Immunosuppression and Clinical Disease

Current Author Addresses: Dr. Schnittman and Mr. Greenhouse: Building 10, Room 11B-13, National Institutes of Health, Bethesda, MD 20892.

Drs. Psallidopoulos and Salzman: Department of Microbiology, Preclinical Science Building, Room LM-12, Georgetown University, Washington, DC 20007.

Dr. Baseler: Building 469, Room 6, NCI-Frederick Cancer Research Facility, PO Box B, Frederick, MD 21701.

Dr. Fauci: Building 31, Room 7A03, National Institutes of Health, Bethesda, MD 20892.

Dr. Lane: Building 10, Room 11B-09, National Institutes of Health, Bethesda, MD 20892.

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-I).

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-I 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+ T cells and deteriorating clinical course in HIV-infected patients.

Article and Author Information

From the National Institutes of Health, Bethesda, Maryland; Georgetown University, Washington, D.C; and the Frederick Cancer Research Facility, Frederick, Maryland. For current author addresses, see end of text.
Grant Support: In part by federal funds from the Department of Health and Human Services under contract number N01-CO-74102.
Requests for Reprints: Steven M. Schnittman, MD, Building 10, Room 11B-13, National Institutes of Health, Bethesda, MD 20892.