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Tenofovir alafenamide works well and improves kidney and bone markers in older people living with HIV
Liz Highleyman, 2016-11-10 07:20:00
A co-formulation of tenofovir
alafenamide (TAF) plus emtricitabine, used with a third antiretroviral drug,
maintained viral suppression as well as tenofovir disoproxil fumarate (TDF)
plus emtricitabine in older individuals, and was associated with improvements
in kidney function and bone density, which may be of greater concern for this
group, according to a presentation last week at IDWeek 2016 in New Orleans.
Gilead Sciences' tenofovir disoproxil
fumarate (brand name Viread) and a co-formulation of TDF
and emtricitabine (Truvada) are among
the most widely used antiretrovirals. These drugs are also part of the Atripla, Eviplera and Stribild single-tablet regimens. TDF is generally safe and well tolerated,
but it can cause modest bone loss and kidney problems in susceptible individuals.
of the Descovy, Genvoya and Odefsey
combination pills, but not sold separately) is a pro-drug
formulation that delivers the active drug to HIV-infected cells more
efficiently than TDF. TAF produces adequate intracellular drug levels with
smaller doses, which means lower concentrations in the blood and less drug
exposure for the kidneys, bones and other organs and tissues.
The study described at
IDWeek compared the TAF/emtricitabine and TDF/emtricitabine co-formulations when used in triple
antiretroviral therapy regimens with various third drugs.
This study included 663
people initially taking TDF/emtricitabine plus a third drug, but not using a
single-tablet regimen. At enrolment they had undetectable viral load (< 50 copies/ml) and near-normal kidney
function (estimated GFR > 50 ml/min).
Participants were randomly
assigned to either stay on TDF/emtricitabine or switch to TAF/emtricitabine as an NRTI backbone, while staying on the same third drug. Just under
half were using boosted protease inhibitors while the rest were on unboosted
third agents including NNRTIs and integrase inhibitors. The TAF dose was 10mg
if taken with boosted protease inhibitors or 25mg with unboosted third agents;
the TDF dose was always 300mg.
The overall results, presented at this years Conference on Retroviruses and Opportunistic
Infections (CROI 2016), showed that the regimens worked equally well, with 94%
in the TAF/emtricitabine group
and 93% in the TDF/emtricitabine
group having undetectable viral load at 48 weeks. Kidney function and bone
mineral density improved in people who switched to TAF/emtricitabine.
At IDWeek Eric Daar of UCLA Medical Center presented
findings from a subgroup analysis of older participants in the study – age 50
or over – a group that is at increased risk for kidney and bone problems as
they age, and therefore may benefit most from using TAF rather than TDF.
This analysis included 150 people randomised to TAF/emtricitabine and 144 assigned to
TDF/emtricitabine. Nearly 90%
were men, more than 80% were white and
the median age was approximately 55 years (range 50-79). The median baseline
CD4 count was approximately 660 cells/mm3 in the TAF/emtricitabine
arm and 590 cells/mm3 in the
TDF/emtricitabine arm. The median eGFR was about 91 ml/min, just over
40% had hypertension and 7% had diabetes – known risk factors for kidney
Mirroring the overall results, viral suppression rates at 48 weeks were
high in both groups: 96% in the TAF/emtricitabine
arm and 94% in the TDF/emtricitabine
arm. Only 1% experienced virological failure and 4% in both arms were missing
Both regimens were generally safe and
well tolerated, but kidney and bone outcomes favoured TAF/emtricitabine. In both arms, 10%
of participants experienced drug-related adverse events and 4% had serious
adverse events; 3% in the TAF/emtricitabine
arm and 1% in the TDF/emtricitabine
arm discontinued treatment due to adverse events, none of which were kidney- or
People who switched to the TAF/emtricitabine arm saw a
median eGFR increase of +8.8 ml/min compared to +2.5 ml/min in the TDF/emtricitabine arm, a significant
difference. Urine biomarkers improved in the TAF/emtricitabine arm while
worsening in the TDF/emtricitabine
arm: protein-to-creatinine ratio (-15% vs +10%),
albumin-to-creatinine ratio (-2% vs +16%), retinol blinding
protein-to-creatinine ratio (-17% vs +23%) and
beta-2-microglobulin-to-creatinine ratio (-42% vs +26%).
Spine bone mineral density rose by a
mean +1.9% in the TAF/emtricitabine arm, while falling by -0.2% in the TDF/emtricitabine arm. The corresponding changes in hip bone density were
+1.0% and -0.3%, respectively.
Blood lipid levels increased slightly in the TAF/emtricitabine group, but the
total cholesterol-to-HDL ratio stayed about the same. This occurs because
tenofovir reduces lipid levels and this effect is diminished with TAF compared
In people age 50 and older, "Efficacy and
safety [of TAF/emtricitabine],
including renal and bone safety profile, [were] consistent with overall study
population and those <50 years," the researchers summarised.
"is an important backbone for older patients living with HIV," they
concluded. "This is of particular importance as the population living with
HIV ages and experiences more renal and bone-related comorbidities."
Speaking from the audience, Joseph Eron of the
University of North Carolina noted that age 50 or 55 is really not that old,
and it would be useful to look at continuous trends extending to older ages when
kidney problems and bone loss become more common.