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. Design: Prospective, multicenter cohort study. Setting: Four university-based clinical centers participating in the Multicenter AIDS Cohort Study. Patients: 1604 men infected with HIV-1. Measurements: The markers compared were oral candidiasis (thrush) or fever; serum neopterin levels; serum β₂- 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 β₂-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 10 000 copies/mL, 10 001 to 30 000 copies/mL, and more than 30 000 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.