Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk

OBJECTIVE To compare the efficacy, safety, and impact on lipid fractions of switching from a ritonavir-boosted protease inhibitor (PI/r) to a dolutegravir (DTG) regimen. METHODS HIV type 1-infected adults more than 50 years or with a Framingham score more than 10% were eligible if plasma HIV RNA less than 50 copies per ml for at least 24 weeks while on a PI/r regimen. Patients were randomized to switch to DTG or to remain on PI/r. Primary endpoints were: proportion maintaining HIV RNA less than 50 copies per ml and percentage change from baseline of total cholesterol at week 48. RESULTS In total, 415 patients (32 sites in six European countries) were randomized: 205 to DTG and 210 to continue PI/r. About 89% were men, 87% more than 50 years, 74% had a Framingham score more than 10%, with a median CD4 cell count of 617 cells per μl and suppressed viremia for a median of 5 years. At week 48, in the intent-to-treat analysis, treatment success rate was 93.1% in DTG group and 95.2% in PI/r group (difference -2.1%, 95% confidence interval -6.6 to 2.4, noninferiority demonstrated). There were four virological failures with DTG and one with PI/r with no emergent resistance mutations. There was no significant difference in severe adverse events or grade 3 or 4 adverse events or treatment modifying adverse events. Total cholesterol and other lipid fractions (except high-density lipoprotein cholesterol) improved significantly (P < 0.001) in the DTG group regardless of PI/r at baseline. CONCLUSION Switching to a DTG regimen in virologically suppressed HIV type 1 patients with high cardiovascular disease risk was noninferior, and significantly improved lipid profiles.