A phase IV, open-label three-arm study investigating the impact of a combination of tenofovir disoproxil fumarate/emtricitabine with raltegravir or dolutegravir or elvitegravir/cobicistat on renal function in HIV-1 antiretroviral naïve patients.

Objectives: Tenofovir DF (TDF) remains one of the preferred backbone agents for naïve HIV patients starting antiretroviral treatment (ART). The impact of TDF on renal function and metabolic parameters may vary by anchor agent. We investigated the impact of TDF in combination with 3 different integrase inhibitors on tubular and glomerular function, and metabolic parameters in ART-naïve patients.Methods: Sixty patients with normal renal function were randomised (20 per arm) to TDF/emtricitabine (FTC) plus either raltegravir (RAL) (400 mg b.d.), dolutegravir (DTG) or elvitegravir/cobicistat (EVG/c) for 48 weeks.Results: 57 patients completed the study. Significant increases in RBP/creatinine ratio at week 24 were seen in all arms [RAL +4.7 µg/mmol (CI 0.43 to 8.98, p = 0.032); DTG +4.96 µg/mmol (CI 0.77 to 9.15, p = 0.021); EVG/c +6.95 µg/mmol (CI 2.53 to 11.36, p = 0.002)], although this was not sustained to week 48 in the RAL arm. Similar changes across the arms were observed for urinary α1microglobulin (RAL +6.20 mg/L, p = 0.030; DTG +6.30 mg/L, p = 0.025; EVG/c +8.15 mg/L, p = 0.003). Urinary ß2microglobulin significantly increased at week 24 with DTG and EVG/c but remained unchanged in the RAL arm. Glomerular filtration measured with CKD-EPI creatinine-cystatin C increased significantly in the RAL arm at week 24 through 48 but declined modestly in other two arms. Total and LDL cholesterol decreased in the RAL arm, but increased in the EVG/c arm, with no significant changes in the DTG arm. Weight increased significantly from baseline with DTG but not RAL or EVG/c.Conclusion: INSTIs in combination with TDF/FTC impact differently on tubular microproteinuria, eGFR, metabolic markers and weight. Use of TDF/FTC with RAL had the least tubular effects and the most favorable metabolic profile.

Use of Coronary Artery Calcium Scoring to Improve Cardiovascular Risk Stratification and Guide Decisions to Start Statin Therapy in People Living With HIV.

BACKGROUND: Cardiovascular disease (CVD) risk assessment remains a critical step in guiding decisions to initiate primary prevention interventions in people living with HIV (PLWH). SETTING: We investigated whether coronary artery calcium (CAC) scoring allowed a more accurate selection of patients who may benefit from statin therapy, compared with current risk assessment tools alone. METHODS: Cross-sectional analysis of PLWH over 50 years old who underwent CAC scoring between 2009 and 2019. Framingham Risk score (FRS), QRISK2 and D:A:D scores were calculated for each participant at the time of CAC scoring and statin eligibility determined based on current European guidelines on the prevention of CVD in PLWH. RESULTS: A total of 739 patients were included (mean age 56 ± 5, 92.8% male, 84% white). Among 417 (56.4%) candidates for statin therapy based on FRS ≥10%, 174 (23.5%) had no detectable calcification (CAC = 0). Conversely, 145 (19.6%) patients with detectable calcification (CAC > 0) were identified as low-risk (FRS < 10%). When compared with FRS, CAC scoring reclassified CVD risk in 43.1% of patients, 145 (19.6%) to a higher risk group that could benefit from statin therapy and 174 (23.5%) statin candidates to a lower risk group. QRISK2 and D:A:D scores performed similarly to FRS, underestimating the presence of significant coronary calcification in 21.1% and 24.9% respectively and overestimating risk in 16.9% and 18.8% patients with CAC = 0. CONCLUSIONS: Establishing a decision-model based on the combination of conventional risk tools and CAC scoring improves risk assessment and the selection of PLWH who would benefit from statin therapy.