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Better Virologic Control After Switch From Boosted ATV/TDF/FTC to E/C/F/TAF
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15th European AIDS Conference, October 21-24, 2015, Barcelona
EACS: Switching From Boosted Atazanavir Plus Emtricitabine /Tenofovir Disoproxil Fumarate to a Tenofovir Alafenamide-Based Single-Tablet Regimen: Week-48 Data in Virologically Suppressed Adults (10/28/15)
Mark Mascolini
Forty-eight weeks after randomization to continued boosted atazanavir plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or to a single-tablet tenofovir alafenamide (TAF)-containing regimen, a significantly higher proportion of people randomized to switch had a viral load below 50 copies [1]. People who swapped the atazanavir/TDF regimen for TAF plus elvitegravir/cobicistat and FTC (E/C/F/TAF) had significant improvements in bone mineral density and kidney markers and moderately but significantly worse lipid changes.
TAF is the tenofovir prodrug that controls HIV well in antiretroviral-naive people as part of E/C/F/TAF and has a better renal and bone marker profile than TDF-containing regimens [2]. An ongoing trial randomized adults with a viral load below 50 copies on a TDF regimen for at least 48 weeks and an estimated glomerular filtration rate (eGFR) at or above 50 mL/min to switch to E/C/F/TAF or continue the TDF combination. A prespecified analysis assessed 48-week outcomes in people taking ritonavir- or cobicistat-boosted atazanavir plus TDF/FTC who got randomized 2-to-1 to switch to E/C/F/TAF or continue the TDF regimen.
The study group included 385 people taking atazanavir/ritonavir and 216 taking atazanavir/cobicistat with TDF/FTC. Of these 601 people, 199 continued their TDF combination and 402 started open-label E/C/F/TAF. Median age of both groups was 41 years, and 14% were women. About two thirds were white and about 15% black. Median CD4 count stood at 659 in the E/C/F/TAF group and 633 in the continued-TDF group. Respective eGFRs were 92 and 93 mL/min. About 10% of participants had grade 1 proteinuria, with little difference between groups.
After 48 weeks, 97% randomized to E/C/F/TAF and 92% who continued TDF had a viral load below 50 copies for a significant treatment difference of 5.1% (95% confidence interval [CI] 0.9% to 9.2%, P = 0.006). There were 5 failures in the E/C/F/TAF group and 4 in the TDF group (1.2% versus 2%); there were no failures with resistance in either group and no discontinuations because of lack of efficacy.
While 1% in the E/C/F/TAF arm stopped treatment because of adverse events, 3% in the TDF arm stopped for that reason, including 1 case of Fanconi syndrome. Serum creatinine did not change through 48 weeks in the E/C/F/TAF arm while rising 0.03 mg/dL in the TDF arm (95% CI -0.05 to -0.01, P = 0.003). Levels of 4 urine protein markers, including 2 markers of tubular proteinuria, declined significantly with the switch to E/C/F/TAF (P < 0.001 for all) while climbing in the TDF arm.
Total cholesterol, low- and high-density lipoprotein (LDL and HDL) cholesterol, and triglycerides all rose slightly but significantly with the switch to E/C/F/TAF while staying nearly unchanged in the control arm. Total-to-HDL cholesterol ratio remained unchanged through 48 weeks in the E/C/F/TAF group while rising fractionally in the TDF group (3.6 to 3.7).
DXA-measured spine bone mineral density (BMD) rose an average 2.18% through 48 weeks in the E/C/F/TAF arm while waning 0.54% in the TDF arm, a significant difference (P < 0.001). Hip BMD climbed an average 1.74% with E/C/F/TAF and fell 0.54% with continued TDF (P < 0.001). Proportions of participants with osteopenia of the spine (-3.9%) or hip (-11.5%) fell in the group that switched to E/C/F/TAF while remaining unchanged in the control arm.
The researchers attributed the significant improvements in renal and bone safety after the switch to E/C/F/TAF to the approximately 90% lower in plasma tenofovir levels seen with TAF than TDF.
References
1. Rijnders B, Stephan C, Lazzarin A, et al. Switching from ritonavir or cobicistat boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate to a tenofovir alafenamide-based single tablet regimen: week 48 data in virologically suppressed adults. 15th European AIDS Conference, October 21-24, 2015, Barcelona. Abstract PS10/3.
2. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385:2606-2615. www.natap.org/2015/HIV/PIIS067361560616X.pdf
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