HIV-1 RNA LEVELS AND THE DEVELOPMENT OF CLINICAL-DISEASE

Objective: To assess the prognostic value of HIV RNA levels for predic ting clinical disease independently of the CD4 lymphocyte count in pat ients on antiretroviral therapy. Design: Cohort of HIV-infected patien ts from two trials of lamivudine therapy.Patients: For 620 patients ra ndomized in the North American NUCA3001 and NUCA3002 trials of lamivud ine, HIV RNA levels were measured (median, seven measures per patient) and CD4 counts were assessed at a central laboratory (median, 13 coun ts per patient). Patients were in the 1993 Centers for Disease Control and Prevention (CDC) stages A (n = 439), B (n = 135) or C (n = 46) at baseline. Outcome measures: For patients who were in CDC stage A at b aseline we considered the ability of HIV RNA levels and CD4 counts to predict the development of CDC stage B or C disease. A Cox proportiona l hazards model was used. In a second analysis, patients who were AIDS -free at baseline were considered, and the endpoint was AIDS (CDC stag e C). Results: Patients' initial CD4 counts ranged (5-95% centiles) fr om 104 to 529x10(6)/l (median, 274x10(6)/l) and HIV RNA levels from 1 900 to 339 680 copies/ml (median, 44 240 copies/ml). For the first ana lysis, with CDC stage B or C disease as endpoint, both the most recent HIV RNA level and CD4 count predicted the development of clinical dis ease [relative hazard (RH) for HIV RNA, 1.96 per 10-fold difference in HIV RNA; 95% confidence interval (CI), 1.41-2.73; P=0.0001; and RH fo r CD4 count, 1.82 per twofold difference in CD4 count; 95% CI, 1.27-2. 56; P=0.0009]. When both HIV RNA and CD4 count were included in a mult iple regression model, both markers provided information additional to that given by the other (RH for HIV RNA, 1.75; 95% CI, 1.23-2.50; P=0 .002; and RH for CD4 count, 1.40; 95% CI, 0.95-2.07; P=0.09). In the s econd analysis, with AIDS as endpoint, both HIV RNA level (P=0.02) and CD4 count (P=0.004) were independently associated with clinical progr ession. These results were essentially unchanged after adjustment for treatment arm (zidovudine/lamivudine versus control arms). Conclusion: The HIV RNA level shows ability to predict the development of clinica l disease and may thus be of importance in addition to the CD4 count i n patient monitoring.