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It has been suggested that the plasma HIV RNA level is a better predictor of AIDS and death than the CD4 lymphocyte count. We assessed whether the prognostic value of plasma virus levels was different according to the CD4 count.Prospective cohort study of HIV-infected patients followed for a median of 2.91 years (range, 0.02–4.54).Department of Infectious Diseases at Rigshospitalet, Copenhagen, Denmark.A group of 255 HIV-infected individuals with an initial measurement of CD4 lymphocyte count and plasma HIV RNA.Survival time.The plasma HIV RNA (median 101 410 copies/ml; range (range 200–7 200 000) and the CD4 lymphocyte count (median 250 cells × 106/l; range 1–1247) were negatively correlated (Pearson r = −0.53; P < 0.00001). Of the 255 patients, 110 died during follow-up. Overall, a higher HIV RNA level was associated with increased risk of death, but the association was smaller in patients with lower CD4 lymphocyte counts (test for interaction P < 0.0001). In patients with CD4 count below 50 cells × 106/l the association between HIV RNA and risk of death was not statistically significant (relative hazard per 10-fold higher HIV RNA level was 1.53; P = 0.11; adjusted for age and CD4 count) while that between the CD4 count and risk of death was highly significant (relative hazard per 50% lower CD4 count 1.38; P = 0.005; adjusted for age and HIV RNA level).Patients were relatively lightly treated with antiretroviral drugs both before and during this study. In this situation, it appears that the HIV RNA level has a relatively weak association with risk of death in patients with advanced HIV infection and that the CD4 lymphocyte count is probably more useful in assessing prognosis.