Among HIV-infected, virologically suppressed black adults, emtricitabine/tenofovir alafenamide (FTC/TAF) showed improvements in renal and bone safety compared to emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), according to Dr Jason A Flamm, from Kaiser Permanente, Sacramento, and co-authors in an IDWeek 2017 presentation.
At Week 96, FTC/TAF “demonstrated high rates of virologic suppression, improved bone and renal safety, and small increases in lipids, with no treatment differences in total cholesterol:HDL ratio,” reported Flamm and colleagues. “Efficacy and safety of FTC/TAF in black patients were similar to those in nonblack patients.”
“Given the safety advantage of TAF vs TDF from a renal standpoint, FTC/TAF is an important backbone for black patients living with HIV,” the authors concluded.
The research team performed a 96-week subgroup analysis by race for pre-specified efficacy and post-hoc safety outcomes, using data from a randomized, double-blind, active-controlled study (n=663) in virologically suppressed adults with HIV infection who switched to FTC/TAF from FTC/TDF (n=333) vs. continuing FTC/TDF while taking the same third agent (n=330).
20% of patients identified themselves as black. Baseline viral load, CD4 cell counts, renal laboratory parameters, and bone mineral density (BMD) were similar between the 2 treatment arms for blacks and non-blacks.
At Week 96, virologic success among black patients was 87% for FTC/TAF vs. 88% for FTC/TDF and 89% vs. 90% for non-blacks.
Adverse events leading to study drug discontinuation occurred in 1 (2%) black patient in the FTC/TDF group and 4% of non-black patients (8 patients [3%] in the FTC/TAF group and 3 [1%] in the FTC/TDF group). Adverse events leading to discontinuation included (1 patient each): insomnia/mood alteration, dysphagia, atrial fibrillation, diarrhoea, peripheral oedema, overdose, lymphoma, increased serum creatinine, rectal tenesmus, feeling abnormal/headache, renal tubular disorder, and acquired lipodystrophy/affective disorder.
The renal tubular disorder case involved a non-black patient in the FTC/TDF group. Renal biomarkers at Week 96 demonstrated a difference in the median change in eGFR of 10.1 for FTC/TAF group-patients vs. 4.0mL/min in the TDF/TAF group (P=0.06) among black patients. That difference in median change in eGFR was similar to the 10.0 vs 3.9mL/min changes reported for non-blacks.
Among black patients, median percent-change in urine protein:Cr and urine β2M:Cr were significantly different between those in the FTC/TAF group and the FTC/TDF group (-21.5% vs. 6.3% and -16.6% vs. 26.8%, respectively; P=0.01 and P<0.001).
In general, FTC/TAF showed improvements in renal and bone safety vs. FTC/TDF along with sustained efficacy at Week 96. “These results support switching to FTC/TAF from FTC/TDF for the treatment of HIV-1 infection in Black adults,” concluded Flamm.
Background: Black adults are disproportionately affected by HIV.
Methods: We conducted a 96-week subgroup analysis by race (Black vs. non-Black) for efficacy (pre-specified) and safety (post-hoc) from a randomized, double blind, active-controlled study in virologically suppressed HIV-infected individuals who switched to emtricitabine/tenofovir alafenamide (FTC/TAF) from FTC/tenofovir disoproxil fumarate (FTC/TDF) vs continuing FTC/TDF while remaining on the same third agent.
Results: Of 663 treated patients, 136 (20.5%) self-identified as Black (FTC /TAF n=69, FTC /TDF n=67). Baseline viral load, CD4 counts, renal laboratory parameters, and bone mineral density (BMD) were similar between the two arms within Blacks and non-Blacks. For Blacks, virologic success by FDA snapshot algorithm at week 96: FTC /TAF 87.0% vs. FTC /TDF 88.1%; for non-Blacks 89.0% vs 89.7%. Few participants discontinued study drug due to adverse events in either subgroups (FTC/TAF vs FTC/TDF: Black 0 vs. 1.5%; non-Black, 3.0% vs. 1.1%). In assessment of renal and bone safety using estimated glomerular filtration rate (eGFR), renal biomarkers, and BMD, there were differences between two arms that generally favored FTC/TAF over FTC/TDF (Table). In the overall population, no cases of Fanconi syndrome or proximal renal tubulopathy occurred with FTC/TAF; one FTC/TDF participant discontinued study drug due to proximal tubulopathy.
Conclusion: In virologically suppressed Black adults, FTC/TAF demonstrated improvements in renal and bone safety over FTC/TDF with similar sustained efficacy at week 96. These results support switching to FTC/TAF from FTC/TDF for the treatment of HIV-1 infection in Black adults.
Jason A Flamm, Joseph Gathe, Clifford Kinder, Michael Para, Bruce Rashbaum, Sorana Segal-Maurer, David Shamblaw, Michael Wohlfeiler, Benjamin Young, Christine Zurawski, Martin S Rhee