Switching from treatment regimens containing tenofovir/emtricitabine (Truvada, F/TDF) to regimens containing emtricitabine/tenofovir alafenamide (F/TAF) maintains undetectable viral loads and improves renal and bone safety, according to 48-week study results presented at CROI 2016 in Boston.
Although elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya) has already been approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV, tenofovir alafenamide (TAF) by itself -- or in this case, combined with emtricitabine (FTC, Emtriva) -- has not yet been approved and continues to be investigated.
The popular coformulation F/TDF is a part of many recommended first-line treatment regimens and is also approved for pre-exposure prophylaxis (PrEP), However, tenofovir disoproxil fumarate (TDF, Viread) has been associated with kidney and bone toxicities. TAF is a much-discussed improved version of tenofovir, which has shown better kidney and bone safety when used in Genvoya.
The study, which was presented by Joel Gallant, M.D., M.P.H., followed 663 HIV-positive individuals who were already on a regimen containing F/TDF, had achieved undetectable viral loads (< 50 copies/mL) and had an eGFR (estimated glomerular filtration rate -- a measure of kidney health) ≥ 50 mL/min.
At baseline, the median age was 49, 85% were male, and the median eGFR was 100 mL/min (over 90 is considered healthy and below 60 is abnormal). As for treatment, 46% were on regimens containing a boosted protease inhibitor, 28% on regimens containing an integrase inhibitor and 25% were on regimens with a non-nucleoside reverse transcriptase inhibitor (NNRTI).
After randomization, 333 were switched to regimens containing F/TAF and 330 stayed on regimens containing F/TDF.
Virologic Suppression Differences
After 48 weeks, 94.3% of those in the F/TAF group maintained an undetectable viral load compared with 93% in the F/TDF group.
Viral suppression numbers remained similar for both regimens when stratifying by age, race and sex, but with a discrepancy in females, which Gallant attributed to low sample size and administrative difference.
Resistance and drug-related adverse events were rare (well below 1% for each group), while drug discontinuation due to adverse events was low (2.1% for F/TAF versus 0.9% for F/TDF). No cases of proximal renal tubulopathy were observed in either group.
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Kidney Safety Differences
The median eGFR increased by 8.4 mL/min in the F/TAF group, compared with an increase of 2.8 mL/min in the F/TDF group (P < .0001).
Measures of proteinuria (indicators of kidney damage) improved in the F/TAF group but not the F/TDF group, with all differences being statistically significant (P < .001).
Bone Safety Differences
On average, bone mineral density (BMD) increased for the F/TAF group but decreased for the F/TDF group: in the hip +1.14% versus -0.15% (P < .001) and in the spine: +1.53% versus -0.21% (P < .001).
Additionally, more patients in the F/TAF group had greater than 3% increase in BMD at week 48: in the hip 17% versus 9% (P = .003) and in the spine 30% versus 14% (P < .001).
Participants in the F/TAF group had a higher median increase in lipids, with statistically significant differences for total cholesterol, LDL (low-density lipoprotein) cholesterol and triglycerides. However, Gallant noted that the differences were relatively small, with questionable clinical significance.
Gallant also noted that there was no statistical significance between the two groups for total cholesterol/HDL (high-density lipoprotein) ratio, nor was there a difference between groups for participants who started lipid-lowering medications during the study.
These 48-week snapshot results are consistent with results seen in studies of Genvoya. The study is expected to continue through 96 weeks.
F/TAF is currently being reviewed by the FDA in two different doses for combination with other antiretrovirals, as well as in an updated version of rilpivirine/tenofovir/emtricitabine (Complera).