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

- RAL plus unboosted ATV is an option for NRTI- and RTV-sparing dual regimen.
- Of 102 patients observed, 77.5% had virological response after more than 2 years follow-up.
- A concerning rate (18.6%) failed with newly selected mutations.
- Safety and tolerability profile was confirmed, only 4 discontinued for intolerance.
- RAL plus ATV might be considered in selected adherent patients.

BackgroundUnboosted atazanavir with raltegravir has been investigated at 300 mg twice daily showing frequent hyperbilirubinemia and selection of resistance-associated mutations.ObjectivesAtazanavir 200 mg twice daily could increase tolerability and plasma exposure.Study designPatients on atazanavir/raltegravir (200/400 twice daily), with self-reported adherence >95% and no concomitant interacting drugs were retrospectively evaluated.Results102 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).DiscussionSwitch 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.