Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome.
Twenty human immunodeficiency virus-infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n=10) or nevirapine (n=10). Patients treated with the nevirapine-containing regimen experienced significantly greater virologic suppression at week 24 than those not treated with nevirapine (P=.04). Baseline phenotypic drug susceptibility was strongly correlated with outcome in both treatment arms. Subjects with baseline virus phenotypically sensitive to 2 or 3 drugs in the salvage regimen experienced significantly greater virus load suppression than those with baseline virus sensitive to 0 or 1 drug (median week-24 change=-2.24 log and -0.35 log, respectively; P=.01). In conclusion, non-nucleoside reverse transcriptase inhibitors may represent a potent drug in salvage therapy regimens after failure of an indinavir or ritonavir regimen. Phenotypic resistance testing may provide a useful tool for selecting more effective salvage regimens.
Deeks
S G
SG
University of California, San Francisco, AIDS Program. San Francisco General Hospital, San Francisco General Hospital, San Francisco, CA 94110, USA. sdeeks@sfaids.ucsf.edu
Hellmann
N S
NS
Grant
R M
RM
Parkin
N T
NT
Petropoulos
C J
CJ
Becker
M
M
Symonds
W
W
Chesney
M
M
Volberding
P A
PA
D000328:Adult; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D008297:Male; D019888:Nelfinavir / Q000627:therapeutic use; D019829:Nevirapine / Q000627:therapeutic use; D010641:Phenotype; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D016879:Salvage Therapy; D019258:Saquinavir / Q000627:therapeutic use; D000099227:Abacavir
D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir; D019829:Nevirapine; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D019258:Saquinavir; D000099227:Abacavir