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Plasma Viral Load and CD4+ Lymphocytes as Prognostic Markers of HIV-1 Infection

John W. Mellors, MD; Alvaro Munoz, PhD; Janis V. Giorgi, PhD; Joseph B. Margolick, MD, PhD; Charles J. Tassoni, PhD; Phalguni Gupta, PhD; Lawrence A. Kingsley, DrPH; John A. Todd, PhD; Alfred J. Saah, MD; Roger Detels, MD; John P. Phair, MD; and Charles R. Rinaldo Jr., PhD
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For author affiliations and current author addresses, see end of text. Acknowledgment: The authors thank the MACS participants and staff for their dedication. Grant Support: By the National Institute of Allergy and Infectious Diseases with supplemental support grants U01-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041 from the National Cancer Institute. Requests for Reprints: John W. Mellors, MD, Graduate of School of Public Health, 603 Parran Hall, 130 DeSoto Street, University of Pittsburgh, Pittsburgh, PA 15261. Current Author Addresses: Dr. Mellors: University of Pittsburgh, Graduate School of Public Health, 603 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(12):946-954. doi:10.7326/0003-4819-126-12-199706150-00003
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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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Figure 1.
Estimated slopes of CD4+ lymphocyte counts by human immunodeficiency virus type 1 (HIV-1) RNA category.

Vertical bars represent 95% CIs.

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Figure 2.
Kaplan-Meier curves showing acquired immunodeficiency syndrome (AIDS)-free survival by human immunodeficiency virus type 1 (HIV-1) RNA category among groups with different baseline CD4+ lymphocyte counts.Table 2

The five categories of HIV-1 RNA were the following: I, 500 copies/mL or less; II, 501 to 3000 copies/mL; III, 3001 to 10 000 copies/mL; IV, 10 001 to 30 000 copies/mL; and V, more than 30 000 copies/mL. Numbers in parentheses are the sample sizes of the groups at baseline. Groups that were too small to provide estimates were omitted. The following table (see ) lists the numbers of participants in each group after 3, 6, and 9 years.

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Figure 3.
Probability of developing the acquired immunodeficiency syndrome (AIDS) according to human immunodeficiency virus type 1 (HIV-1) concentration and CD4+ lymphocyte count.P

The values are derived from the likelihood ratio test using Cox regression. Mean 95% Cls were derived from 500 bootstrap samples using the percentile method.

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