A prospective comparison of the two main indications of efavirenz in 2001 highly active antiretroviral therapy (HAART) regimens: first-line versus salvage use.

OBJECTIVE To determine the efficacy of efavirenz introduction in first-line HAART compared with salvage multidrug regimens. PATIENTS AND METHODS Prospective 15 month comparison of 107 consecutive HIV-infected patients starting efavirenz, according to laboratory and clinical outcome of first-line versus rescue drug use, therapeutic history and association of selected antimicrobial agents: naive patients were compared with nucleoside reverse transcriptase inhibitor (NRTI)-experienced patients in the first group, and patients in the second group who had one or more NRTI changed when starting a rescue treatment containing one or more novel protease inhibitors (PIs) were compared with those who did not. RESULTS Efavirenz was administered with one or more novel NRTIs to 55 patients (27 antiretroviral-naive and 28 patients experienced with NRTIs only), compared with 52 patients who needed a multidrug salvage regimen after two or more failures of a 15-40 month PI-containing regimen. In an intention-to-treat analysis, con-sidering early interruption or an unsatisfactory virological course as a failure, only one patient on salvage therapy completed a favourable 15 month follow-up, compared with 31 patients experiencing first-line efavirenz-based HAART (P < 0.0001). The immunological response was less affected in both intensity and duration in patients undergoing rescue therapy. While no significant outcome difference was detected in the first group between naive and NRTI-experienced patients, among the salvage subjects the change of one or more NRTIs seemed to significantly improve virological and immunological outcome. Viral genotyping detected at least the K103N mutation in 41% of the 78 evaluable patients, despite lack of exposure to efavirenz and related compounds. Salvage patients had a significantly greater frequency of non-nucleoside RTI (NNRTI) resistance compared with the first-line group (P < 0.0001), in proportion to the extent of mutations affecting other drug classes (P < 0.0001). CONCLUSION An efavirenz-based initial triple drug HAART proved significantly more effective than efavirenz adjunct to a rescue treatment performed after repeated failures of PI-based regimens. The unsatisfactory response of the salvage group was probably due to diffuse cross-resistance descending from previous therapy, even when NNRTIs were never administered.