Adverse Metabolic Changes May Accompany Switch From TDF- to TAF-containing Antiretroviral Therapy

By Reuters Staff

March 17, 2021

NEW YORK (Reuters Health) - Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) in antiretroviral therapy (ART) regimens raises the risk of significant weight gain and worsening blood lipid levels in people living with HIV, the Swiss HIV Cohort Study team reports.

Tenofovir-based ART is now standard first-line therapy in all major HIV-treatment guidelines. Compared with TDF, TAF has a favorable renal and bone safety profile, but concerns about metabolic complications linger, Dr. Bernard Surial of the University Hospital of Bern and colleagues note in Annals of Internal Medicine.

To investigate further, they studied 4,375 adults living with HIV who received TDF-containing ART for at least six months. Their median age was 50 years, 26% were women and 52% had a normal BMI. Of the total, 3,484 (80%) switched to TAF and 891 (20%) continued on TDF.

After 18 months, switching to TAF was associated with an adjusted average weight gain of 1.7 kg compared with 0.7 kg with continued TDF use (P<0.001).

Among those with a normal BMI at the outset and available follow-up data at 18 months, 211 of 1,529 (14%) patients who switched to TAF became overweight or obese after 18 months, compared to 35 of 419 (8.4%) who continued TDF, a significant difference.

Switching to TAF also led to increases in adjusted mean total cholesterol (0.25 mmol/L), HDL cholesterol (0.05 mmol/L), LDL lipoprotein cholesterol (0.12 mmol/L) and triglyceride (0.18 mmol/L) levels after 18 months.

The researchers say their estimates were robust across subgroups of patients regardless of whether TAF was administered together with protease inhibitors, nonnucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors.

"Our study is among the largest to date investigating the effect of switching from TDF to TAF on weight and metabolic outcomes within a well-defined and nationally representative cohort," they write.

"Recommendations on the use of TAF should balance its advantages (renal and bone safety) with its potential harms, including metabolic complications. The decision to prefer TAF over TDF as a component of ART should be individualized and accompanied by the repeated assessment of cardiometabolic risk factors, including weight and lipids," they advise.

In addition, they call for further study exploring the mechanisms leading to metabolic changes in this population.

The study was funded by the Swiss National Science Foundation. Dr. Surial did not respond to a request for comment by press time.

SOURCE: https://bit.ly/3cB0CHM Annals of Internal Medicine, online March 15, 2021.

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