Study: Only one of two HIV drugs of the same type reduces cholesterol and causes weight loss – possible cause found in the small intestine

HIV treatment has changed dramatically in recent years, with modern treatments making it possible for HIV patients to live as long as the mainstream population. However, it has been observed that patients have a higher risk of developing associated diseases, such as coronary artery disease.

Kai Kauppinen studied two different prodrug forms of tenofovir. The older drug – tenofovir disoproxil fumarate (TDF) – has been associated with adverse effects on renal function and the bones. However, it has also been found to decrease cholesterol and body weight.

When TDF is changed to the newer and more expensive tenofovir alafenamide (TAF), cholesterol levels and body weight increase but the drug has less adverse renal and bone effects. The aim of Kauppinen's research group was to find out what causes these metabolic differences between the two prodrug forms of tenofovir. The results of a two-year study have now been published in Clinical Infectious Diseases.

A total of 12 patients who take TDF and 12 who take TAF were recruited for the study, and it was carried out in collaboration with several different specialities at the HUS Inflammation Center. Samples taken from the patients’ small intestine showed that participants in the TDF group had flatter villi than those in the TAF group, indicating possible mucosal damage caused by the drug. This may lead to decreased nutrient absorption and a subsequent decrease in cholesterol and body weight.

HIV medication may have affected duodenal mucosa

The study also examined the effect of the different prodrug forms of tenofovir on concentrations of vitamins and micronutrients in the blood and on the mitochondria in small intestine cells. Previous studies have shown that TDF can cause mitochondrial damage in renal cells, so the damage in the small intestine was also thought to be a result of mitochondrial damage.

The majority of measured vitamin concentrations were lower in the TDF group than in the TAF group, although no statistically significant difference was observed. Surprisingly, signs of mitochondrial damage were visible in both groups and in nearly all the patients. It is unclear whether this damage was caused by the tenofovir medication or by the actual HIV infection.

There has been no previous knowledge that HIV medications could affect the duodenal mucosa. The flatter villi now detected in the duodenal mucosa may explain the decrease in cholesterol values and weight loss in TDF patients.

“Current HIV medications are safe and well tolerated and they have very few adverse effects. With consideration to the patients’ increased risk of coronary artery disease, it is important to try to determine which HIV medications are most favourable for patients,” says Kauppinen.

“TDF is less expensive and the decrease in cholesterol and body weight associated with its use is good for the patient when the higher risk of developing, for example, coronary artery disease is taken into account. However, it is still important to ensure that TDF does not cause significant vitamin or micronutrient deficiencies in patients. More extensive studies with larger amounts of patient data are needed in order to clarify the matter,” says Kauppinen.

Kauppinen KJ, Aho I, Sjöblom N, Tynninen O, Suomalainen A, Schwab U, Zhao F, Arkkila P, Sutinen J. Effect of Two Forms of Tenofovir on Duodenal Enterocytes - a Hypothesis for Different Effect of TDF and TAF on Body Weight and Plasma Lipids. Clin Infect Dis. 2024 Jul 23.

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