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.
Already enrolled ANRS CO3 Aquitaine Cohort patients with virologic failure were included in this study after starting a raltegravir-based regimen (400 mg twice a day, week 0). Virologic success was defined by 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).
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 virologic success: 4 (44%), 14 (82%) and 21 (87%) of patients with a genotypic sensitivity score <1, [1–2[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 rise 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).
Raltegravir plus OBT provided a good virologic success rate in highly pre-treated patients under clinical routine conditions.
Keywords: Adult, Anti-HIV Agents, pharmacokinetics, therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Drug Resistance, Viral, Female, HIV Infections, drug therapy, immunology, virology, HIV-1, classification, genetics, isolation & purification, Humans, Male, Middle Aged, Pyrrolidinones, pharmacokinetics, therapeutic use, Treatment Outcome, Viral Load
Keywords: Raltegravir, antiretroviral treatment experienced patients, viro-immunological response, integrase resistance mutations