Prospective comparison of first-line nelfinavir therapy versus nelfinavir introduction in rescue antiretroviral regimens.
In order to establish the role of the protease inhibitor nelfinavir in current clinical practice, a prospective 18-month open-label comparison of efficacy and tolerability of nelfinavir was performed among HIV-infected patients who either incorporated nelfinavir in their first-line highly active antiretroviral therapy (HAART) regimen (group A, 57 patients), or who added nelfinavir to a rescue antiretroviral regimen (following at least two attempts with protease inhibitor-based HAART) (group B, 67 patients). All evaluable data were analyzed according to the prior and concurrent antiretroviral therapy, including genotypic resistance assays for patients undergoing salvage therapy. A significantly better virologic outcome (as expressed by a > 2 log(10) drop of plasma viremia versus baseline or attainment of undetectable levels), was shown among patients belonging to group A versus group B, where a number of genotypic mutations possibly elicited by previous anti-HIV treatment strongly impaired a potent and sustained nelfinavir activity. On the whole, the immunologic response (as expressed by the mean CD4(+) lymphocyte count versus baseline), substantially paralleled the virologic one in all analyzed subgroups, but a tendency toward a maintained immunologic competence was also observed in the majority of patients experiencing virologic failure. Nelfinavir introduction was sufficiently safe, because a limited percentage of patients suffered from mild-to-moderate, novel, or continuing adverse events, which proved significantly more frequent in the salvage group but did not affect adherence to HAART.
Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna, S. Orsola Hospital, Bologna, Italy. manfredi@med.unibo.it
Roberto
R
Manfredi
Leonardo
L
Calza
Francesco
F
Chiodo
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007239:Infections / Q000188:drug therapy*; D019888:Nelfinavir / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D016879:Salvage Therapy; D014157:Transcription Factors
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D014157:Transcription Factors; C118437:negative elongation factor; D019888:Nelfinavir