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Bone density improves in people who switch from tenofovir DF to tenofovir alafenamide
Liz Highleyman, 2017-03-27 07:40:00

After three years, tenofovir alafenamide (TAF) for first-line HIV treatment was better at suppressing viral load and safer for the bones and kidneys than the older tenofovir disoproxil fumarate (TDF), researchers reported at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI 2017) last month in Seattle. Another study showed that people with low bone density who switched from TDF to TAF saw improved bone health, including a reduction in osteoporosis

Gilead Sciences' TDF (Viread, also in the Truvada, AtriplaEviplera and Stribild co-formulations) has been one of the most widely used antiretroviral drugs. It is generally considered safe and well-tolerated, but it can cause kidney toxicity in susceptible individuals and bone loss soon after starting treatment.

TAF (part of the Descovy, Genvoya and Odefsey co-formulations) is a pro-drug that delivers its active agent more efficiently to HIV-infected cells. TAF produces adequate intracellular levels with much lower doses, which means lower concentrations in the blood plasma and less drug exposure for the kidneys, bones, and other organs and tissues.

At CROI 2015 researchers presented 48-week results from a pair of phase 3 studies comparing single-tablet regimens containing TAF and TDF used for initial antiretroviral therapy. At this year's meeting Jose Arribas of La Paz University Hospital in Madrid, Spain, gave an update with 144-week data.

Study 104 and Study 111 together included 1733 previously untreated people; most were men and the median age was 34 years. They had well-controlled HIV disease with a median CD4 T-cell count of approximately 400 cells/mm3 and normal kidney function with a median estimated glomerular filtration rate (eGFR) of approximately 115 ml/min.

Participants were randomly assigned to start a once-daily single-tablet regimen containing elvitegravir, cobicistat and emtricitabine with either 25mg TAF or 300mg TDF (Genvoya or Stribild).

At 48 weeks 92% of people in the TAF arm and 90% in the TDF arm achieved HIV RNA < 50 copies/ml, showing that TAF was non-inferior to TDF.

At 144 weeks the viral suppression rates were 84% and 80%, respectively, and at this point the TAF regimen was statistically superior to the TDF combo. Twelve participants (1.4%) in each arm experienced virological failure with drug resistance.

The 48-week data showed that overall drug safety profiles were similar in both arms, with few participants discontinuing treatment due to adverse events (8 on TAF and 13 on TDF). But while most discontinuations for this reason happened early in the TAF arm, they continued to occur over time in the TDF arm, so by week 144 there was a significant difference in favour of TAF.

Most notably, there were 12 kidney-related events leading to discontinuation – including four cases of renal tubulopathy – in the TDF arm but none in the TAF arm. Likewise, six people in the TDF arm but none in the TAF arm stopped early due to bone-related events. Changes in renal biomarkers were significantly smaller and there was significantly less hip and spine bone loss in the TAF arm. Fasting lipids increased more among people on TAF, however.

"These longer-term data support the use of elvitegravir/cobicistat/emtricitabine/TAF as a safe, well tolerated and durable regimen for initial and on-going HIV-1 treatment," the researchers concluded.