Switching from TDF to TAF linked to higher BMI and cardio risk

A 110-person retrospective study found increasing body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk after a switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF), even though participants changed no other drugs in their regimen. [1]

Thomas Jefferson University researchers said clinical implications could include the need to treat more people with statins to keep ASCVD risk in line.

Switching from TDF to TAF spares antiretroviral-treated people unwanted impacts on kidney and bone. But ongoing research indicates that trading TDF for TAF hurts cholesterol numbers and boosts weight, while the impact on ASCVD risk remains uncertain. To explore these issues, Thomas Jefferson researchers conducted a retrospective study to assess changes in BMI and ASCVD risk score when changing from TDF to TAF while maintaining other antiretrovirals in the regimen.

The analysis included 40- to 75-year-old adults who took a TDF-containing regimen for at least one year, during which they never had a viral load above 200 copies/mL. Everyone replaced TDF with TAF without changing their other antiretrovirals and had one year of observation after the switch. In the year before and the year after the change, researchers calculated median BMI, weight, total cholesterol, ‘bad’ low-density lipoprotein (LDL) cholesterol, ‘good’ high-density lipoprotein (HDL) cholesterol, and triglycerides. Using 2018 American College of Cardiology/American Heart Association guidelines, they figured ASCVD risk scores at the switch and 6 to 12 months afterwards. To assess changes in BMI and ASCVD risk score, the investigators used repeated measures generalised estimating equations.

The 110 study participants averaged 50 years in age, 73% were men, 58% black, 34.5% white, 5.5% Hispanic, and 2% Asian. While 31% were normal weight, 4% were underweight, 28% overweight, and 37% obese. The group spent a median of eight years taking antiretrovirals. Almost half (49%) took an integrase inhibitor with TDF, while 29% took an NNRTI, 16% a PI, and the rest something else.

Median weight, BMI, total and LDL cholesterol, and ASCVD risk score all climbed significantly after TAF replaced TDF: weight 185.4 to 190.5 lb (p<0.01), BMI 28 to 28.2 kg/m² (p<0.01), total cholesterol 173.8 to 195.0 mg/dL (p<0.01), LDL cholesterol 98.6 to 112.1 mg/dL (p<0.01), and ASCVD risk score 6.9% to 8.1% (p<0.01). HDL cholesterol and triglycerides rose nonsignificantly and total-to-HDL cholesterol ratio did not change.

Regression analysis controlling for female sex linked switching from TDF to TAF to a 0.45-kg/m²jump in expected BMI. Regression analysis controlling for age, female sex, race, and time since HIV diagnosis tied swapping TDF for TAF to a 13% boost in expected ASCVD risk score.

The Thomas Jefferson researchers argued it was unlikely that rising BMI represented a “return to health” because participants had long-standing HIV infection well-controlled by antiretroviral therapy. Although observed BMI changes were small, the investigators added, they could have clinical relevance since even small BMI changes can affect lifetime risk for diabetes and ASCVD. The 13% jump in ASCVD risk score, they noted, lifted more than half of the study group to scores that would require statin therapy.

Now that the FDA has cleared TAF/FTC for preexposure prophylaxis, the findings could also have implications for steady PrEP users.