Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine - AIDS clinical trials group protocol 320

Background: A substantial proportion of patients with HIV infection will no t respond to antiretroviral therapy. Early predictors of response to treatm ent are needed to identify patients who are at risk for treatment failure. Objective: To determine predictors of virologic and clinical response to in dinavir, zidovudine, and lamivudine therapy. Design: observational analysis of one treatment group in a phase III trial. Setting: 40 AIDS Clinical Trials units. Patients: 489 patients receiving Indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 x 10(9) cells/L or less after 8 or more weeks o f study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline a nd week 8. Measurements: HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illn ess or death. Results: Patients' levels of HIV-1 RNA at the 8th study week of therapy pre dicted whether patients would achieve virologic suppression to below 500 (o r 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/m L at week 24 was achieved In 71% of patients whose level at week 8 had been less than 500 copies/mL, 53% of those with a level of 500 copies/mL or mor e and at least 2-log(10) copies/mL reduction since baseline, 29% of those w ith a level of 500 copies/mL or more with a 1- to 1.99-log(10) copies/mL re duction, and 9% of those with a level of 500 copies/mL or greater and less than 1-log(10) copies/mL reduction since baseline (P < 0.001). HIV-1 RNA le vel at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2% of the patients with a week-8 HIV-1 RNA level less than 500 copies /mL, 2.3% of patients with 500 copies/mL or greater and at least 2-log(10) copies/mL reduction since baseline, 4.9% of patients with 500 copies/mL or greater and 1- to 1.99-log(10) copies/mL reduction since baseline, and 10.6 % of patients with 500 copies/mL or greater and less than 1-log(10) copies/ mL decrease since baseline (P = 0.009). After adjustment for HIV-1 RNA leve l, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count greater than or equal to 0.10 x 10(9) cells/L, 1.4 7 [95% Cl, 1.00 to 2.16] compared with <0.050 x 10(9) cells/L; relative ris k for patients with a week-8 CD4 count of 0.05 to 0.099 x 10(9) cells/L, 0. 98 [Cl, 0.61 to 1.57] compared with <0.050 x 10(9) cells/L). After adjustme nt for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 x 109 cell s/L or greater (compared with <0.05 x 10(9) cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [Cl, 0.09 to 0.67]). Conclusions: The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical out comes.