title: Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor-experienced persons.
abstract: The efficacy of sequential protease inhibitor therapy was studied in 16 human immunodeficiency virus (HIV) 1-infected persons in whom saquinavir with multiple nucleoside reverse transcriptase (RT) inhibitors (NRTI) had failed. Nelfinavir plus two NRTIs (new or continued) resulted in minimal (0.59 log RNA copies/mL) and transient (8 weeks) suppression of plasma HIV RNA levels. Rapid failure was surprisingly associated with baseline presence of protease gene mutation L90M (P=.04) in the absence of D30N and with RT mutations D67N (P<.01), K70R/S (P=.02), and K219Q/W/R/E (P<.01). Ten patients were subsequently switched to indinavir plus nevirapine and 2 NRTIs, resulting in a median 1.62 log reduction in plasma HIV RNA, with 3 patients maintaining 400 copies/mL for 24 weeks. These results suggest that nelfinavir may have limited utility after saquinavir failure, particularly without potent concomitant therapy. Combining an NRTI with a new protease inhibitor for rescue may improve response.
authors.affiliation: Center For AIDS Research at Stanford, Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA. drjl@mindspring.com
authors.forename: J
authors.initials: J
authors.lastname: Lawrence
authors.forename: J
authors.initials: J
authors.lastname: Schapiro
authors.forename: M
authors.initials: M
authors.lastname: Winters
authors.forename: J
authors.initials: J
authors.lastname: Montoya
authors.forename: A
authors.initials: A
authors.lastname: Zolopa
authors.forename: R
authors.initials: R
authors.lastname: Pesano
authors.forename: B
authors.initials: B
authors.lastname: Efron
authors.forename: D
authors.initials: D
authors.lastname: Winslow
authors.forename: T C
authors.initials: TC
authors.lastname: Merigan
mesh_terms: D000328:Adult; D004351:Drug Resistance; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000009:adverse effects / Q000627:therapeutic use; D019829:Nevirapine / Q000627:therapeutic use; D019338:Polypharmacy; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019888:Nelfinavir; D019258:Saquinavir