Featured news from NHIVNA
HIV-related news from NAM
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, Atripla, Eviplera 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
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,
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.