Michael Carter
Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) is associated with an increase in lipids, but this is reversed when switching back to TDF, German researchers report in the December 1 issue of AIDS. Lipids increased in more than two-thirds of those who made the switch, but cholesterol and triglyceride levels decreased again after returning to TDF, especially in individuals who had experienced the greatest lipid increases when switching to TAF.
Half of the study participants switched to TDF when inexpensive generic versions of the drug became available. Therefore, reverting from TAF to the older tenofovir formulation by people experiencing elevated lipids could have potential clinical benefits for those involved and also help alleviate the financial strain on cash-strapped healthcare providers.
"The results of our study confirm the reversible pharmacological effect on the lipid profile of switching from TDF to TAF and vice versa," the researchers commented. "The changes observed in cholesterol in our study are similar to those reported with less potent statin agents."
Cardiovascular disease is now a leading cause of serious illness and death among people living with HIV. This has been linked to elevated lipid levels. This means that preventing cardiovascular disease, including lowering lipid levels, is now a priority in HIV care.
TDF, the older formulation of tenofovir, has long been a mainstay of antiretroviral therapy. Unlike many other HIV drugs, it does not cause increases in lipids and may even have a beneficial effect on cholesterol and triglyceride profiles. However, TDF is not without side effects and has been associated with reductions in bone mineral density and kidney dysfunction. TAF, the newer formulation of tenofovir, is gentler on bones and kidneys, but previous research suggests that, compared with TDF, it causes increases in total cholesterol, LDL (“bad”) cholesterol, and triglycerides.
The researchers wanted to see if the lipid increases that accompanied a switch from TDF to TAF were reversible when therapy was switched back to TDF. Therefore, they designed a retrospective study involving 385 people receiving HIV care in Dusselfdorf who made this switch. Other components of their antiretroviral regimen and lipid-lowering therapies remained constant. This meant the researchers could be confident that any lipid changes were related to the use of the different tenofovir formulations.
Lipid levels were measured just before switching therapy from TDF to TAF. Researchers reported changes in cholesterol and triglycerides 12 and 24 weeks after this therapy change. Data on lipid changes were also presented among those who returned to TDF, again at 12- and 24-week follow-up intervals.
All participants had an undetectable viral load. The mean age at the start of the study was 49 years, 90% were male, the mean BMI was 23.9 kg/m2 (and therefore within the healthy range), and the mean CD4 cell count was 752.
The average duration of TDF therapy was six years. A minority (13%) were taking lipid-lowering therapy, 7% had total cholesterol above 240 mg/dL, and one-fifth had triglycerides above 200 mg/dL.
"Cholesterol and triglyceride levels decreased again after returning to TDF, especially in individuals who had experienced the greatest increases when switching to TAF."
The mean total cholesterol before switching to TAF was 186 mg/dL. Increases were recorded after the switch at the 12-week (206 mg/dL) and 24-week (204 mg/dL) follow-up points. The increase in total cholesterol after replacing TDF with TAF was particularly associated with older age and overweight.
Similarly, triglycerides increased from an average of 153 mg/dl before the change in treatment to 176 mg/dl in both follow-up intervals after the change.
La información detallada sobre los perfiles de lípidos estaba disponible para 70 participantes. Esto mostró aumentos significativos después de cambiar a TAF en el colesterol LDL (p <0.005) y el colesterol HDL (p <0.001). La relación colesterol total / HDL se mantuvo sin cambios.
Después de la introducción del TDF genérico en Alemania, la mitad de los participantes cambiaron nuevamente al TDF. Estas personas habían experimentado aumentos en los lípidos en línea con los observados en la población general del estudio después de cambiar a TAF. Sin embargo, 24 semanas después de volver a TDF, el colesterol total había vuelto a una media de 185 mg / dl (p <0,001) y los triglicéridos habían disminuido a una media de 157 mg / dl (p <0,05).
Two-thirds of the people had increases in total cholesterol of at least 10 mg/dL after switching from TDF to TAF, and 31% experienced an increase of more than 20 mg/dL. People with the largest increases in total cholesterol (30 mg/dL vs. less than 10 mg/dL) after the first switch showed the most pronounced decreases after switching back to TDF.
There was no evidence that the use of lipid-lowering drugs or other anti-HIV agents had an effect on these results.
"Switching from TDF/emtricitabine to TAF/emtricitabine leads to a marked and reversible increase in total cholesterol and other proatherogenic lipid fractions in a relevant proportion of patients," the authors conclude.
References
Milinkovic A et al. Reversible effect on lipids when switching from tenofovir disoproxil fumarate to tenofovir alafenamide and vice versa. AIDS 33: 2387-2391, 2019.
DOI: 10.1097/QAD.0000000000002350
From: http://www.aidsmap.com/news/dec-2019/lipid-increases-after-switching-tdf-taf-are-reversible-when-treatment-changed-back