DISCREPANT RESPONSES TO TRIPLE COMBINATION ANTIRETROVIRAL THERAPY IN ADVANCED HIV DISEASE

Objectives: To determine the clinical, virological and immunological o utcome in a cohort of unselected patients receiving triple combination therapy for more than 1 year. Methods: Prospective follow-up of a coh ort of 162 unselected, protease inhibitor-naive, antiretroviral-experi enced patients with advanced HIV disease, treated with indinavir combi ned with two nucleoside analogues. Results: The mean CD4 cell count an d plasma HIV RNA level in the study group at baseline were 69 +/- 5 x 10(6)/l and 4.75 +/- 0.07 log(10) copies/ml, respectively. Five per ce nt of patients died prematurely or were lost to follow-up. Fifty-seven per cent of patients responded to therapy, as assessed by a sustained increase in CD4 cell counts above 50 x 10(6)/l and a decrease in plas ma HIV RNA greater than 1 log(10) copies/ml, throughout 12.1 months of follow-up. Seventeen per cent of patients were immunological and viro logical non-responders. Twenty-one per cent of patients exhibited disc repant virological and immunological responses to treatment, of whom o ne-half failed to exhibit significant increases in CD4 cells despite a virological response to therapy and one-half exhibited increased CD4 cell counts in the absence of significant decrease in plasma viral loa d. The incidence of AIDS-defining events in the latter group of patien ts was similar to that of responder patients, whereas their incidence was higher in patients who failed to exhibit a virological and immunol ogical response and those who failed to increase CD4 cells despite a s ignificant decrease in viral load. Conclusion: Our observations of dis crepant immunological and virological responses to treatment raise the issue of the significance of persistent elevated levels of plasma HIV RNA and of the relevance of measurements of plasma viral load for ass essing the efficacy of antiretroviral therapy in patients whose CD4 ce ll counts increase despite the absence of significant decrease in plas ma HIV viral load. (C) 1998 Lippincott-Raven Publishers.