Protease inhibitors as initial therapy for individuals with an intermediate risk of HIV disease progression: is more necessarily better?

Objective: To compare three possible therapeutic strategies for the treatme nt of patients with an intermediate risk of HIV disease progression. Design: Mathematical modeling based on assumptions derived from published d ata. Methods: A parametric survival model was fitted to empirical data to descri be the survival trajectory of untreated individuals. it was assumed that su ccessful treatment decreases the risk of disease progression during the fir st year after its introduction by a constant that is dependent on the magni tude of the initial drop in HIV viral load. Thereafter, individual members of the treatment cohort follow different pathways, depending on the duratio n of the initial response or, in case of virologic failure, the response to a new drug regimen. Results: Sub-groups of patients starting therapy with two nucleoside revers e transcriptase inhibitors (NRTI) or two NRTI and a protease inhibitor had the highest instantaneous risk of disease progression at the end of the 5-y ear follow-up period. Patients who started therapy with two NRTI and a non- NRTI had the lowest likelihood of progression to AIDS or death at 5 years o f follow-up. This is because, in the case of the subgroup whose initial tre atment included a protease inhibitor, failure rates due to non-adherence to therapy are high and response to salvage therapy is limited by past protea se inhibitor experience. Conclusions: Despite the superior virologic potency of the protease inhibit or-containing regimens, in this analysis other strategies performed equally well or even better. In the absence of solid empirical data and until the advent of antiretroviral regimens that are shown to be safe, simple to take , and maximally suppress viral load, caution may be required in selecting t he long-term therapy for patients with less advanced HIV disease. (C) 1999 Lippincott Williams & Wilkins.