Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection.

Background: The optimal antiretroviral treatment for patients who have huma n immunodeficiency virus (HIV) viremia despite treatment with nucleoside re verse-transcriptase inhibitors (nucleoside analogues) remains uncertain. We studied treatment with regimens that combined two nucleoside analogues, at least one of which was new, with the protease inhibitor nelfinavir, the no nnucleoside reverse-transcriptase inhibitor efavirenz, or both. Methods: The study included 195 patients who had been treated with nucleosi de analogues only, and had a plasma HIV type 1 (HIV-1) RNA level of at leas t 500 copies per milliliter. Patients were randomly assigned to receive, in addition to two nucleoside analogues, nelfinavir, efavirenz, or nelfinavir plus efavirenz. The primary end point was a plasma HIV-1 RNA level of less than 500 copies per milliliter at week 16. A secondary end point was the c omposite of the HIV-1 RNA levels measured at weeks 40 and 48. Results: At week 16 and at weeks 40 and 48, the proportions of patients in whom a plasma HIV-1 RNA level of less than 500 copies per milliliter was ac hieved were, respectively, 81 percent and 74 percent in the nelfinavir-plus -efavirenz group, 69 percent and 60 percent in the efavirenz group, and 64 percent and 35 percent in the nelfinavir group. Quadruple therapy resulted in a higher rate of viral suppression in both the short term (P=0.03) and t he long term (P=0.001) than did triple therapy with nelfinavir. Triple ther apy with efavirenz conferred a higher rate of long-term suppression than tr iple therapy with nelfinavir (P=0.004). Quadruple therapy also achieved a h igher rate of virologic suppression than triple therapy with efavirenz (P=0 .008). Conclusions: In HIV-infected patients previously treated with nucleoside an alogues, treatment with nelfinavir plus efavirenz and at least one new nucl eoside analogue achieves a higher rate of viral suppression than do regimen s with nucleoside analogues and nelfinavir or efavirenz alone. (N Engl J Me d 2001;345:398-407. Copyright (C) 2001 Massachusetts Medical Society.