JAC Advance Access originally published online on March 31, 2009
Journal of Antimicrobial Chemotherapy 2009 63(6):1251-1255; doi:10.1093/jac/dkp114
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Original research |
Virological and immunological response in HIV-1-infected patients with multiple treatment failures receiving raltegravir and optimized background therapy, ANRS CO3 Aquitaine Cohort
1 Inserm, Unit 897 Epidemiology and Biostatistics, Bordeaux, France 2 University Victor Segalen Bordeaux 2, ISPED, Bordeaux School of Public Health, Bordeaux, France 3 Department of Clinical Pharmacokinetics and Clinical Pharmacy and EA 2968, University Victor Segalen, Bordeaux, France 4 Pharmacy Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France 5 Department of Virology and EA 2968, Bordeaux University Hospital, University Victor Segalen, Bordeaux, France 6 Department of Internal Medicine and Infectious Diseases, Bordeaux University Hospital, University Victor Segalen, Bordeaux, France
Received 11 February 2009; returned 17 February 2009; revised 4 March 2009; accepted 5 March 2009
* Corresponding author. ISPED (Case 11), 146 rue Leo Saignat, 33076 Bordeaux Cedex, France. E-mail: Linda.Wittkop{at}isped.u-bordeaux2.fr
Background: The efficacy of raltegravir plus optimized background therapy (OBT) has been demonstrated for antiretroviral (ARV)-experienced HIV-1-infected patients in randomized clinical trials. We studied viro-immunological response, pharmacokinetic parameters and genotypic test results in an observational cohort of multiple ARV class-experienced patients starting a raltegravir-based regimen.
Methods: Already enrolled ANRS CO3 Aquitaine Cohort patients with virological failure were included in this study after starting a raltegravir-based regimen (400 mg twice a day, week 0). Virological success was defined by the plasma HIV-1 RNA level [viral load (VL)] <2.7 log10 copies/mL at week 12 and <1.7 log10 copies/mL at week 24. One patient was excluded from further analysis (no follow-up after week 4).
Results: Fifty-one patients [male/female = 43/8, median age = 48 (interquartile range = 43, 55) years] were included. At week 0, median CD4 count was 244 (110; 310)/mm3 and median VL was 4.2 (3.6, 4.7) log10 copies/mL. At week 24, 39 (78%) patients experienced virological success: 4 (44%), 14 (82%) and 21 (87%) patients with a genotypic sensitivity score <1, 
1 and <2 and 2 (P = 0.02), respectively. Raltegravir-related mutations emerged in 9 of 11 failing patients (82%): Q148H/R (n = 5), N155S/H (n = 3) and S230N (n = 1). Median CD4 increases from week 0 to week 4 and week 24 were 28 (–4, 85) and 57 (0, 156) cells/mm3, respectively. A poor immune response was independently associated with a lower VL decline (week 0 to week 12) [odds ratio (OR): 3.5, 95% confidence interval (CI): 1.4, 8.4, for 1 log10 less] and CD4+% at baseline (OR: 2.6, 95% CI: 0.97, 8.3, for 10% lower).
Conclusions: Raltegravir plus OBT provided a good virological success rate in highly pre-treated patients under clinical routine conditions.
Keywords: antiretroviral treatment-experienced patients , viro-immunological response , integrase resistance mutations
The first two authors contributed equally to this study.
Present address: Department of Immunology and EA 2968, Bordeaux University Hospital, University Victor Segalen, Bordeaux, France.
See the Acknowledgements section.