Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study.
BACKGROUND
Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients.


METHODS
Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction).


RESULTS
Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15).


CONCLUSIONS
In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.
Division of Infectious Diseases & Hospital Epidemiology, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, Switzerland.
Jan
J
Fehr
Tracy R
TR
Glass
Séverine
S
Louvel
François
F
Hamy
Hans H
HH
Hirsch
Viktor
V
von Wyl
Jürg
J
Böni
Sabine
S
Yerly
Philippe
P
Bürgisser
Matthias
M
Cavassini
Christoph A
CA
Fux
Bernard
B
Hirschel
Pietro
P
Vernazza
Gladys
G
Martinetti
Enos
E
Bernasconi
Huldrych F
HF
Günthard
Manuel
M
Battegay
Heiner C
HC
Bucher
Thomas
T
Klimkait
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral / Q000502:physiology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D013557:Switzerland; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D019380:Anti-HIV Agents
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