Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients.
OBJECTIVE
To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors.


METHODS
Retrospective study in two German tertiary care treatment centres.


METHODS
A total of 198 HIV-infected patients treated with protease inhibitors in 1996.


METHODS
Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures.


RESULTS
A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001).


CONCLUSIONS
An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.
Fätkenheuer
G
G
Department of Internal Medicine I, University of Cologne, Germany.
Theisen
A
A
Rockstroh
J
J
Grabow
T
T
Wicke
C
C
Becker
K
K
Wieland
U
U
Pfister
H
H
Reiser
M
M
Hegener
P
P
Franzen
C
C
Schwenk
A
A
Salzberger
B
B
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D017211:Treatment Failure
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir; D019258:Saquinavir; D019438:Ritonavir