Efficacy, safety and pharmacokinetics of atazanavir (200 mg twice daily) plus raltegravir (400 mg twice daily) dual regimen in the clinical setting

Background Unboosted atazanavir with raltegravir has been investigated at 300 mg twice daily showing frequent hyperbilirubinemia and selection of resistance-associated mutations. Objectives Atazanavir 200 mg twice daily could increase tolerability and plasma exposure. Study design Patients on atazanavir/raltegravir (200/400 twice daily), with self-reported adherence >95% and no concomitant interacting drugs were retrospectively evaluated. Results 102 patients [72.5% male, age 46.4 years (42–54), BMI 24 kg/m2 (22–26)] were included. CD4+ T lymphocytes were 417 cell/μL (302–704) and 76 patients (74.5%) had HIV-RNA <50 copies/ml. After 123 weeks 18.6% patients showed virological failure and 3.9% discontinued for intolerance. Available genotypes showed selection of major integrase (7/10 patients) and protease resistance-associated mutations (5/13 patients). In patients switching with dyslipidemia (n = 67) total, LDL cholesterol and triglycerides significantly decreased. Patients switching with eCRCL<60 ml/min (n = 27) had no significant changes while patients with eCRCL >60 ml/min showed significant decrease (−9.8 ml/min, p = 0.003) at 96-weeks. Atazanavir and raltegravir trough concentrations were 321 ng/mL (147–720) and 412 ng/mL (225–695). Self-reported non-adherence (n = 4) was significantly associated with virological failure (p = 0.02); patients with virological success had borderline longer previous virological control (33 vs. 18 months, p = 0.07). Discussion Switch to atazanavir/raltegravir was safe and well tolerated allowing optimal drugs’ plasma exposure. However, a concerning rate (18.6%) failed with newly selected mutations and stopped ATV/RAL because of DDI and intolerance issues or were lost to follow-up. This regimen might be considered in selected patients, without history of protease inhibitors failure or HBV infection, showing optimal adherence and prolonged suppression.