TDF weight-suppressing effect

[Jim Allen]

I had a quick read-through, interesting but nothing new as far as I am aware. It seems to confirm that TDF has a limited weight-suppressing or protective effect that other HIV meds do not have.

Aidsmap article in full:
https://www.aidsmap.com/news/apr-2024/switching-taf-tdf-leads-weight-loss

Switching from tenofovir alafenamide (TAF) to the older formulation of tenofovir disoproxil (TDF) resulted in modest weight loss in people with HIV in the Swiss HIV Cohort, researchers report in the journal Clinical Infectious Diseases.

Switching from TAF to TDF also brought benefits in the forms of reduced cholesterol and triglycerides.

In contrast, switching from TAF-containing treatment to a two-drug combination of dolutegravir/lamivudine or injectable cabotegravir/rilpivirine did not lead to any changes in weight.

Of those who switched, 196 (18%) swapped TAF for TDF, 565 (52%) switched to dolutegravir/lamivudine, 115 (10%) to injectable cabotegravir/rilpivirine and 94 (18%) to another antiretroviral combination.

As this was an observational study rather than a randomised trial, the researchers adjusted for confounding factors that might also affect weight (age, sex, Black race, CD4 count and weight at the beginning of follow-up, time on antiretroviral treatment, use of integrase inhibitors, level of physical activity, smoking and use of other medications known to affect weight).

Overall, after adjusting for confounding factors, switching from TAF was associated with a weight loss of 0.60kg after one year, compared to no change in weight in people taking TAF. However, when analysed by the agent to which people switched, it was apparent that participants only lost weight (a median of 1.89kg) if they switched to TDF. Weight remained stable in people who switched to other agents or drug combinations.

Weight loss after switching was greater in women and Black people, and in people who had gained at least 10% in body weight after starting TAF, irrespective of what they switched to.

In a review of weight changes in clinical trials of newer antiretrovirals, also published in Clinical Infectious Diseases, a group of HIV clinicians concludes that weight tends to increase towards the societal norm in people with HIV after starting antiretroviral treatment. Any difference between regimens is explained by the weight-suppressive effects of TDF or efavirenz rather than weight-additive effects of newer drugs.

They say that anyone considering a switch from TAF to TDF should be aware that the adverse effects of TDF on kidney function on bone mineral density occur more frequently when TDF is used alongside a boosting agent (ritonavir or cobicistat), as these raise tenofovir levels. However, the use of boosted drugs is declining – the most commonly used antiretroviral that requires boosting is darunavir.

In the light of the higher risk of cardiovascular disease in people with HIV and the societal health challenge of obesity, Dr Andrew Hill asks whether the weight-suppressive and lipid-lowering effects of TDF should be considered as an unanticipated benefit of the drug. With this in mind, “clinicians need to decide whether to use TDF, which has the unexpected benefit of causing reductions in weight and lipids, or using TAF, which has lesser effects on markers of bone and renal function.”

Related: 2020
https://www.poz.com/article/study-sheds-light-weight-gain-switching-new-tenofovir
“These data suggest that differences in weight gain between TAF and TDF are likely driven by removal of TDF-associated weight suppression,” the researchers concluded.