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

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

Research output: Contribution to journalArticle

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
StatePublished - Jun 15 1997
Externally publishedYes

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Virus Diseases
Viral Load
HIV-1
Acquired Immunodeficiency Syndrome
Lymphocytes
CD4 Lymphocyte Count
Oral Candidiasis
RNA
Neopterin
Serum
Cohort Studies
Fever
Branched DNA Signal Amplification Assay
Multicenter Studies
Disease Progression
HIV

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mellors, J. W., Munoz, A., Giorgi, J. V., Margolick, J. B., Tassoni, C. J., Gupta, P., ... Rinaldo, C. R. (1997). Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Annals of Internal Medicine, 126(12), 946-954.

Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. / Mellors, John W.; Munoz, Alvaro; Giorgi, Janis V.; Margolick, Joseph Bernard; Tassoni, Charles J.; Gupta, Phalguni; Kingsley, Lawrence A.; Todd, John A.; Saah, Alfred J.; Detels, Roger; Phair, John P.; Rinaldo, Charles R.

In: Annals of Internal Medicine, Vol. 126, No. 12, 15.06.1997, p. 946-954.

Research output: Contribution to journalArticle

Mellors, JW, Munoz, A, Giorgi, JV, Margolick, JB, Tassoni, CJ, Gupta, P, Kingsley, LA, Todd, JA, Saah, AJ, Detels, R, Phair, JP & Rinaldo, CR 1997, 'Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection', Annals of Internal Medicine, vol. 126, no. 12, pp. 946-954.
Mellors, John W. ; Munoz, Alvaro ; Giorgi, Janis V. ; Margolick, Joseph Bernard ; Tassoni, Charles J. ; Gupta, Phalguni ; Kingsley, Lawrence A. ; Todd, John A. ; Saah, Alfred J. ; Detels, Roger ; Phair, John P. ; Rinaldo, Charles R. / Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. In: Annals of Internal Medicine. 1997 ; Vol. 126, No. 12. pp. 946-954.
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T1 - Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection

AU - Mellors, John W.

AU - Munoz, Alvaro

AU - Giorgi, Janis V.

AU - Margolick, Joseph Bernard

AU - Tassoni, Charles J.

AU - Gupta, Phalguni

AU - Kingsley, Lawrence A.

AU - Todd, John A.

AU - Saah, Alfred J.

AU - Detels, Roger

AU - Phair, John P.

AU - Rinaldo, Charles R.

PY - 1997/6/15

Y1 - 1997/6/15

N2 - 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.

AB - 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.

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