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Patient Proportion With Above-Target LDL
Rises 70% With TDF-to-TAF Switch
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HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow
Mark Mascolini
After 221 people with HIV switched from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF), the proportion with above-target low-density lipoprotein (LDL) cholesterol rose 1.7-fold from 35% to 60% [1]. University of Milan researchers who conducted the study suggested switching from TDF to TAF might prompt closer cardiovascular risk monitoring and perhaps lifestyle or therapeutic intervention.
Multiple trials document rising lipids when people swap TDF for TAF. Partly because TDF lowers lipids, whether TAF's lipid-boosting impact means anything clinically remains uncertain. To address this question, the Milan team retrospectively analyzed lipid changes in TDF-to-TAF switchers in their clinic.
The study involved everyone trading TDF for TAF without changing the anchor drug in their regimen. Everyone had lipid measures available within the 6 months before and after switching, and no one was taking statins. For each person the researchers calculated a cardiovascular risk score and target LDL cholesterol based on 2016 ESC/EAS dyslipidemia guidelines [2]. The main endpoint was having LDL cholesterol above this target after switching to TAF. The researchers used multivariate logistic regression to identify independent risk factors for out-of-target LDL after the switch.
The 221 study participants included 47 women (21%) and had a median age of 45 and median CD4 count of 640. Almost everyone, 98%, had a viral load below 40 copies. The largest proportion of participants took a regimen including a cobicistat-boosted integrase inhibitor (45.7%) or a nonnucleoside (43.3%), while 6% took a cobicistat-boosted protease inhibitor and 5% an unboosted integrase inhibitor. Median initial LDL cholesterol stood at 105 mg/dL (interquartile range [IQR] 90 to 123). Among 200 people assessed for cardiovascular risk score, 10 (5%) had a high cardiovascular risk score (4.5% to 10%), and 12 (6%) had a very high risk score (at or above 10%).
Median time between study lipid measures was 34 weeks (IQR 19 to 42). Total cholesterol, "bad" LDL cholesterol, "good" HDL cholesterol, and triglycerides all rose significantly after TAF began. Total and LDL cholesterol both climbed about 20% (P < 0.0001 for both), while HDL cholesterol rose about 5% (P < 0.0001). Before the switch 70 of 200 people analyzed (35%) had out-of-target LDL. After the switch that proportion rose to 119 of 200 (60%), a significant jump (P < 0.0001).
In the overall study population and in people with baseline LDL cholesterol below their risk score target, logistic regression identified the same independent predictors of out-of-target LDL with TAF. For the overall group, adjusted odds ratios (aOR) (and 95% confidence intervals) follow:
-- Cobicistat versus cobi-free regimen: aOR 2.4 (1.0 to 5.1), P = 0.03
-- Moderate vs low cardiovascular risk score: aOR 4.7 (1.9 to 11.9), P = 0.0013
-- High or very high vs low cardiovascular risk score: aOR 6.2 (1.3 to 29.8), P = 0.0013
-- Each mg/dL higher LDL at baseline: aOR 1.1 (1.0 to 1.1), P < 0.0001
The researchers cautioned that their analysis is limited by its observational design, use of only 1 lipid measure before and after the TAF switch, and lack of a control group that continued TDF. With those caveats in mind, they concluded that the TDF-to-TAF trade "seems to be associated with worsening in lipid profile, leading to an increased proportion of patients with LDL above their cardiovascular-related target." They encouraged colleagues to monitor cardiovascular risk continuously in people with HIV and to consider lifestyle or therapeutic interventions when appropriate.
References
1. Gazzola L, Tagliaferri G, Mondatore D, et al. Increases in lipid profile after switch from TDF to TAF-based HAART regimens in a cohort of HIV-positive patients: is it clinically relevant? HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow. Abstract P187.
2. Catapano AL, Graham I, Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999-3058. https://academic.oup.com/eurheartj/article/37/39/2999/2414995
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