Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection.
BACKGROUND
The rate of disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1) varies widely, and the relative prognostic value of markers of disease activity has not been defined.


OBJECTIVE
To compare clinical, serologic, cellular, and virologic markers for their ability to predict progression to the acquired immunodeficiency syndrome (AIDS) and death during a 10-year period.


METHODS
Prospective, multicenter cohort study.


METHODS
Four university-based clinical centers participating in the Multicenter AIDS Cohort Study.


METHODS
1604 men infected with HIV-1.


METHODS
The markers compared were oral candidiasis (thrush) or fever; serum neopterin levels; serum beta 2-microglobulin levels; number and percentage of CD3+, CD4+, and CD8+ lymphocytes; and plasma viral load, which was measured as the concentration of HIV-1 RNA found using a sensitive branched-DNA signal-amplification assay.


RESULTS
Plasma viral load was the single best predictor of progression to AIDS and death, followed (in order of predictive strength) by CD4+ lymphocyte count and serum neopterin levels, serum beta 2-microglobulin levels, and thrush or fever. Plasma viral load discriminated risk at all levels of CD4+ lymphocyte counts and predicted their subsequent rate of decline. Five risk categories were defined by plasma HIV-1 RNA concentrations: 500 copies/mL or less, 501 to 3000 copies/mL, 3001 to 10000 copies/mL, 10001 to 30000 copies/mL, and more than 30000 copies/mL. Highly significant (P < 0.001) differences in the percentages of participants who progressed to AIDS within 6 years were seen in the five risk categories: 5.4%, 16.6%, 31.7%, 55.2%, and 80.0%, respectively. Highly significant (P < 0.001) differences in the percentages of participants who died of AIDS within 6 years were also seen in the five risk categories: 0.9%, 6.3%, 18.1%, 34.9%, and 69.5%, respectively. A regression tree incorporating both HIV-1 RNA measurements and CD4+ lymphocyte counts provided better discrimination of outcome than did either marker alone; use of both variables defined categories of risk for AIDS within 6 years that ranged from less than 2% to 98%.


CONCLUSIONS
Plasma viral load strongly predicts the rate of decrease in CD4+ lymphocyte count and progression to AIDS and death, but the prognosis of HIV-infected persons is more accurately defined by combined measurement of plasma HIV-1 RNA and CD4+ lymphocytes.
Mellors
J W
JW
School of Public Health, University of Pittsburgh, PA 15261, USA.
Muñoz
A
A
Giorgi
J V
JV
Margolick
J B
JB
Tassoni
C J
CJ
Gupta
P
P
Kingsley
L A
LA
Todd
J A
JA
Saah
A J
AJ
Detels
R
R
Phair
J P
JP
Rinaldo
C R
CR
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D003663:Decision Trees; D018450:Disease Progression; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D012044:Regression Analysis; D019562:Viral Load
D015415:Biomarkers; D012367:RNA, Viral