Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen.
OBJECTIVE
To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting.


METHODS
The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml.


METHODS
Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0).


RESULTS
At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2.


CONCLUSIONS
In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.
Cozzi-Lepri
Alessandro
A
Royal Free and University College Medical School, London, UK. a.cozzi-lepri@pcps.ucl.ac.uk
Phillips
Andrew N
AN
Ruiz
Lidia
L
Clotet
Bonaventura
B
Loveday
Clive
C
Kjaer
Jesper
J
Mens
Helene
H
Clumeck
Nathan
N
Viksna
Ludmila
L
Antunes
Francisco
F
Machala
Ladislav
L
Lundgren
Jens D
JD
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000032:analysis; D019380:Anti-HIV Agents / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000379:methods; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D018570:Risk Assessment / Q000379:methods; D017211:Treatment Failure; D019562:Viral Load
D000596:Amino Acids; D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors