Impact of genotypic resistance testing on selection of salvage regimen in clinical practice.
OBJECTIVE
To determine whether genotypic resistance testing leads to selection of more potent drug regimens when compared to regimens based on treatment history only.


METHODS
Prospective, tertiary care centre-based study.


METHODS
One-hundred-and-forty-five HIV-infected adults on stable antiretroviral therapy (ART) for >6 months experiencing virological failure.


METHODS
The physicians' decision-making process when choosing a salvage regimen was prospectively documented: at time of virological failure, on 'failing ART', genotyping was performed and a hypothetical 'clinical expert ART' based upon patient's drug history was documented. Subsequently, data on resistance mutations, rating by a decision support software and drug history were used to define 'genotyping ART'. After discussion with the patient, final treatment, 'new personalized ART' was chosen and prescribed. To compare the relative potency of the four ART regimens in a standardized manner, a resistance score ranging from 1 (best) to 8 (worst) based on drug ranking by decision support software was attributed to each ART regimen. Virological and immunological outcomes were analysed based on the magnitude of the resistance score.


RESULTS
Median follow-up was 1.5 years. In all 145 patients, median resistance scores for the stepwise selected ART regimens were: 'failing ART': 4.5, 'clinical expert ART': 1.8, 'genotyping ART': 1.5 and 'new personalized ART': 2. The latter was 1.5 in patients who effectively switched to 'new personalized ART' (n=89). Lower resistance scores translated into significantly improved virological response after initiation of 'new personalized ART'. In multivariable analysis, lower resistance scores, lower baseline HIV RNA levels and use of novel antiretroviral drugs were associated with the probability of reducing plasma viraemia to <50 copies/ml.


CONCLUSIONS
This study suggests that treatment choices including genotype and decision support software were virologically superior to those based on drug history only.
Haupts
Stefan
S
Divisione of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Ledergerber
Bruno
B
Böni
Jörg
J
Schüpbach
Jörg
J
Kronenberg
Andreas
A
Opravil
Milos
M
Flepp
Markus
M
Speck
Roberto F
RF
Grube
Christina
C
Rentsch
Katharina
K
Weber
Rainer
R
Günthard
Huldrych F
HF
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D010818:Practice Patterns, Physicians'; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease