Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen. / Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia; Clotet, Bonaventura; Loveday, Clive; Kjaer, Jesper; Mens, Helene; Clumeck, Nathan; Viksna, Ludmila; Antunes, Francisco; Machala, Ladislav; Lundgren, Jens D; Eurosida Study Group.
In: AIDS, Vol. 21, No. 6, 2007, p. 721-32.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen
AU - Cozzi-Lepri, Alessandro
AU - Phillips, Andrew N
AU - Ruiz, Lidia
AU - Clotet, Bonaventura
AU - Loveday, Clive
AU - Kjaer, Jesper
AU - Mens, Helene
AU - Clumeck, Nathan
AU - Viksna, Ludmila
AU - Antunes, Francisco
AU - Machala, Ladislav
AU - Lundgren, Jens D
AU - Eurosida Study Group
PY - 2007
Y1 - 2007
N2 - OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: 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.
AB - OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: 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.
KW - Adult
KW - Aged
KW - Amino Acids
KW - Anti-HIV Agents
KW - Anti-Retroviral Agents
KW - CD4 Lymphocyte Count
KW - Drug Resistance, Viral
KW - Drug Therapy, Combination
KW - Female
KW - Genotype
KW - HIV Infections
KW - HIV Protease Inhibitors
KW - HIV-1
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation
KW - Reverse Transcriptase Inhibitors
KW - Risk Assessment
KW - Treatment Failure
KW - Viral Load
U2 - 10.1097/QAD.0b013e3280141fdf
DO - 10.1097/QAD.0b013e3280141fdf
M3 - Journal article
C2 - 17413693
VL - 21
SP - 721
EP - 732
JO - AIDS
JF - AIDS
SN - 1350-2840
IS - 6
ER -
ID: 4033738