SAQUINAVIR DELAYS THE EMERGENCE OF ZIDOVUDINE RESISTANCE IN HIV-1 SEROPOSITIVE PATIENTS TREATED WITH COMBINATION THERAPY

During a randomized double-blind study to assess the antiviral activit y of saquinavir (SQV) alone or in combination with zidovudine (ZDV), t he emergence of phenotypic resistance was evaluated in 44 patients tre ated with SQV (13 subjects), ZDV (14 subjects), and SQV plus ZDV (17 s ubjects). A significant (P < 0.05) lower CD4(+) cell count and higher HIV RNA copy number at entry were found in six patients who developed resistant viral strain (3 to ZDV and 3 to SQV) during the first 4 mont hs of treatment. After 1 year, drug-resistant strains (12 to ZDV and 1 4 to SQV) were isolated in 26 out of 37 patients. A significant higher number of patients treated with ZDV alone (10/13) harbored ZDV-resist ant strains compared to patients treated by combination therapy (2/13) ; whereas more than 50% of patients had SQV-resistant strains aside fr om treatment. Early SQV-resistant strains were isolated in a limited n umber of patients treated with SQV alone (3/13). The rates of emergenc e of resistant strains during ZDV or SQV monotherapies are comparable. Combination therapy may delay the emergence of phenotypic resistance to either drugs in the short term and to ZDV, but not to SQV, at least after 1 year. (C) 1998 Wiley-Liss, Inc.