Can Bone Loss be Reversed by Switching Drugs?

Switching from one tenofovir-based regimen to another may help increase bone strength among older people living with HIV whose viral loads are suppressed, according to a recent study in The Lancet HIV.

The team of European researchers started with 167 participants over the age of 60 who had an undetectable viral load and were taking an antiretroviral regimen with tenofovir disoproxil fumarate. TDF has long been known to have potential detrimental impacts on bone health, and those over 60 are at the greatest risk for falls and other injuries where weakened bones can become life-threatening. As more and more people with HIV are living beyond their 70s, the risks posed by TDF become of greater concern.

In the Gilead-funded study, investigators switched two-thirds of participants from TDF to a regimen containing tenofovir alafenamide, elvitegravir, cobicistat, and emtricitabine (brand name Genvoya).

After 48 weeks of treatment, the researchers found that bone mineral density at the spine and hip increased in the TAF group but declined among those who stayed on TDF.

“The increases in bone mineral density observed in these people with HIV after switching from TDF to TAF have potentially important clinical consequences in terms of morbidity and mortality,” the authors noted of the impact of the drugs (and bone density) on the health and longevity of those living with HIV. “The bone mineral density increases were greater than expected in the general population.”

In an accompanying editorial in the journal, Dr. Nicola Gianotti and Dr. Antonella Castagna (not involved in the study) argued that the findings are significant, particularly for older people living with HIV. “This study shows for the first time that bone loss is reversible in people living with HIV aged 60 years or older—i.e., people with physiologically reduced bone mineral density,” they wrote.

Indeed, while it’s been known that TDF can cause bone loss, this is the first time a study has shown that that loss can potentially be reversed while retaining undetectability and viral suppression.

But the study’s findings were not entirely positive for TAF, as the study found that those who switched to Genvoya from TDF also saw an increase in cholesterol, a major risk factor for heart disease.

TDF has been a foundational component of many antiretroviral regimens over the past two decades because it has been proven effective and is well tolerated, but it has been increasingly associated with bone density loss and liver damage. The newer TAF has proven to be safer in relation to bone and kidney health while being as effective as TDF.

Poz folks over 50 face higher risks of conditions associated with aging, including bone loss, but there has been little research done on the benefits of switching from TDF to TAF.

At the beginning of the study about 50 percent of the participants had normal bone density at both the spine and hip. By the end of the study, 56 percent of those on TAF had normal bone density, but the rate had fallen to 46 percent among those remaining on TDF. In addition, those switched to TAF were more likely to see improvements in their preexisting osteopenia (bone weakness).

Kidney function also improved with TAF, but growth in cholesterol and triglycerides, a negative impact, was noted as well. The study’s authors suggested that the rise in cholesterol and its impact on heart health “might be outweighed by the other major concerns noted with TDF, such as potential renal effects and decreased bone mineral density.”

Gianotti and Castagna also called for more research involving women and nonwhite participants, since the majority in this study were white males. Still, they lauded the results, concluding, “We now know that switching from TDF allows a partial recovery of bone mass...which will probably reduce the risk of fractures in this population and improve quality of life in older people living with HIV.”