Increasing viral burden in CD4+ T cells from patients with human immunodeficiency virus (HIV) infection reflects rapidly progressive immunosuppression and clinical disease.
OBJECTIVE
To determine over time the relation between viral burden and immunologic decline in patients with asymptomatic human immunodeficiency virus (HIV) infection.


METHODS
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).


METHODS
National research clinic and academic medical centers.


METHODS
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.


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.
Schnittman
S M
SM
National Institutes of Health, Bethesda, Maryland.
Greenhouse
J J
JJ
Psallidopoulos
M C
MC
Baseler
M
M
Salzman
N P
NP
Fauci
A S
AS
Lane
H C
HC
D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D006679:HIV Seropositivity / Q000276:immunology* / Q000382:microbiology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007108:Immune Tolerance; D007958:Leukocyte Count; D015337:Multicenter Studies as Topic; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012189:Retrospective Studies
D004279:DNA, Viral