Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection

John W. Mellors*, Alvaro Muñoz, Janis V. Giorgi, Joseph B. Margolick, Charles J. Tassoni, Phalguni Gupta, Lawrence A. Kingsley, John A. Todd, Alfred J. Saah, Roger Detels, John P. Phair, Charles R. Rinaldo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1652 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)946-954
Number of pages9
JournalAnnals of internal medicine
Volume126
Issue number12
DOIs
StatePublished - Jun 15 1997

ASJC Scopus subject areas

  • Internal Medicine

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