CTN 299: BEING-W

About The Study

CTN 299 assessed the impact of switching combination antiretroviral therapy (cART) on the bone health of women living with HIV between the ages of 45 and 55 in Canada and Italy. Tenofovir (TDF) is a common component in cART regimens but has been associated with increases the rate of bone mineral density (BMD) loss and decline in kidney function. This study supported by a grant from Gilead Sciences, assessed whether switching from TDF to tenofovir alafenamide (TAF) could help prevent or reverse BMD loss in aging women.

Background

Osteoporosis, which increases the fragility of bone and the chance of fractures by lowering BMD, is common in aging women. Women experience a sharp decline in BMD during menopause. This is why this study was recruiting women in the peri-menopausal period.

Living with HIV increases both the risk and severity of osteoporosis and, since over half of people living with HIV are over the age of 50, it is also a major component of clinical care and research. HIV may increase BMD loss through its effect on the immune system and inflammation and as a result of ART.

TAF is a targeted prodrug form of TDF, meaning that it changes into its active form only after being metabolized in the body, moving directly into target cells. For this reason, TAF accumulates mostly within the cells of the body, not in the blood as TDF does. This is thought to be the reason why cART with TAF/FTC (TAF/emtricitabine) causes significantly less BMD loss than TDF/FTC but has the same antiviral effects (viral suppression rates, CD4 increases, resistance rates, etc.). Little information is available as to whether bone mineral density loss with TDF could be improved by switching to TAF.

Study Approach

Thirty-four women were enrolled in this study. They were between the very early stages of menopause and 10 years post-menopause, from age 45 to 55, on an ART regimen containing TDF/FTC, and had a suppressed viral load. The trial duration was two years per participant.

This study included two groups: the first group had nineteen participants who switched to TAF/FTC immediately and the second group had fifteen participants who remained on TDF/FTC and switched after 48 weeks.

Researchers compared the changes in bone structure and fracture risk as well as the safety and tolerability of the two treatments at 48 weeks and at the end of the study (96 weeks). Thirty participants stayed enrolled for the entire duration of the study.

This international study took place at six Canadian sites (Two in Toronto, one each in Hamilton, Montreal, Quebec City, and Vancouver) and two Italian sites (Milan and Modena) and was co-led by Dr. Giovanni Guaraldi (University of Modena and Reggio Emilia) and CTN National Co-Director, Dr. Sharon Walmsley (University Health Network). The study did not reach the target enrollment because of the restrictions imposed by the COVID pandemic.

Results

The BMD measured at the lumbar spine at 48 weeks showed an increase of 1.97% in the immediate switch group, although the delayed switch arm showed a decrease of 2.32%. After 96 weeks, the immediate switch group showed an increase of 2.33% in BMD compared with a 0.70% in the delayed arm, however this was not statistically significant. Measurements of BMD taken at the hip showed negligible changes in BMD in both groups. Serum creatinine levels were normal throughout the study and there were no changes in renal function, loss of viral control, or serious adverse events. This cohort had reasonably good bone health despite years of HIV and TDF therapy, with rates of osteoporosis and low bone density similar to the general population.

Conclusions

This study demonstrated a trend of increased BMD at the lumbar spine after a switch from TDF to TAF in menopausal and early post-menopausal women living with HIV. TAF was safe and well tolerated and is a good option for women of menopausal age living with HIV.