Background
Integrase strand transfer inhibitors (INSTIs) have good lipid profiles but some studies have reported increased risk of dyslipidaemia and hypertension, particularly when combined with tenofovir alafenamide (TAF). Studying seroconverters on early antiretroviral therapy (ART) minimizes the potential confounding impact of long-term HIV infection on cardiometabolic parameters.
Methods
Included individuals from CASCADE seroconverted 2007-2022, were ≥16 years, initiated ART ≤12 months from seroconversion (SC), had body mass index, CD4 count, and viral load measurements at baseline (ART initiation) and total cholesterol (TCHOL) or triglycerides (TG) or arterial blood pressure (BP) measurements at baseline and post-ART. Evolution of lipid levels was modelled through piecewise linear mixed models with 1 knot at 6 months (based on exploratory analyses) and risk of hyperlipidaemia (TCHOL>240 mg/dL or TG>200 mg/dL or antilipidemic treatment) and hypertension (systolic≥140, or diastolic≥90mmHg or initiation of antihypertensives) using time-to-event methods.
Results
Of 1,555 individuals included in the lipid analyses, 590 initiated INSTI without TAF, 285 INSTI+TAF, 382 protease inhibitor (PI), and 298 non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens. Most (86%) were men who have sex with men, 76% originating from Europe/N. America with median (IQR) age at SC 36 (28-44) years. Median (IQR) baseline TCHOL and TG were 161 (139, 186) and 109 (80, 156) mg/dL, respectively. In multivariable models, INSTI+TAF was associated with the fastest TCHOL increase after month 6 of treatment (p<0.001), and faster TG increase only during the first 6 months (p=0.038) compared to NNRTIs. INSTIs without TAF were only associated with a relatively slow increase in TCHOL after month 6 (p=0.027) compared to NNRTIs. In 1189 individuals with no baseline hyperlipidaemia, only PIs were significantly associated with increased hazard of developing hyperlipidaemia (aHR=1.75 vs. NNRTIs; 95% CI:1.26-2.43; p=0.001). Risk of developing hypertension in 1417 hypertension-free at baseline individuals was elevated in those on INSTI+TAF but not INSTI without TAF (aHR=1.51; 95%CI:1.07-2.13; p=0.019 and aHR=1.14; 95%CI:0.85-1.53; p=0.392, respectively).
Conclusions
Lipid levels and BP appear to rapidly increase even at this early stage of infection. Our findings stress the importance of informed ART regimen decisions, acknowledging the potential for different effects on cardiometabolic parameters.