Switching from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen: data in virologically suppressed adults through 48 weeks of treatment
Background: Despite a favorable efficacy and safety profile, TDF-based regimens may be associated with renal toxicity and reduced bone mineral density (BMD). TAF is a novel tenofovir prodrug in which TFV plasma levels are 90% lower than seen with TDF, thereby reducing off-target side effects. Week 48 data in patients switching to a once-daily fixed dose combination regimen containing elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg, and TAF 10mg (E/C/F/TAF) are described.
Methods: Virologically suppressed adults (HIV-1 RNA < 50 copies/mL) with normal renal function taking one of 4 different TDF-based regimens for at least 48 weeks were randomized 2:1 to receive E/C/F/TAF or to retain their prior TDF-based regimen. Following randomization, all treatments were open-label.
Results: Of 1196 patients completing at least 48 weeks of treatment, 799 received E/C/F/TAF and 397 received their prior TDF regimen: E/C/F/TDF, 31.9%; EFV/FTC/TDF, 26.1%; ATV/RTV + FTC/TDF, 26.8%; ATV/COBI + FTC/TDF, 15.0%. Virologic success < 50 copies/mL occurred in 95.6% on E/C/F/TAF and 92.9% on FTC/TDF + 3rd Agent (weighted difference: 2.7%; 95% CI: -0.3% - +5.6%), with virologic failure in 1.1% and 1.3% of patients, respectively. General safety was similar between the arms. The mean percent change (SD) in hip BMD: +1.95% (3.0) for E/C/F/TAF and -0.14% (3.0) for FTC/TDF+3rd Agent (p< 0.001); the mean percent change (SD) in spine BMD: +1.86% (3.1) for E/C/F/TAF and -0.11% (3.7) for FTC/TDF+3rd Agent (p< 0.001). There were no cases of Fanconi Syndrome on E/C/F/TAF and one case on FTC/TDF+3rd Agent. For patients on either a COBI or RTV boosted regimen prior to randomization, the estimated GFR increased 1.8 mL/min for E/C/F/TAF and decreased 3.7 mL/min for FTC/TDF+3rd Agent (p< 0.001). As shown in the table, multiple measures of quantitative proteinuria, including tubular proteinuria, had statistically significant improvements for patients switching to E/C/F/TAF as compared with those retaining their prior TDF-based regimen.
| Median % Change from Baseline to Week 48 | E/C/F/TAF | FTC/TDF + 3rd Agent | Significance |
| Urine Protein: Creatinine (UPCR) | -18.5% | +9.4% | p<0.001 |
| Urine Albumin: Creatinine (UACR) | -18.4% | +5.3% | p<0.001 |
| Retinol Binding Protein: Creatinine (RBP:CR) | -32.9% | +15.7% | p<0.001 |
| Beta-2-Microglobulin: Creatinine (B2MG:CR) | -49.2% | +14.4% | p<0.001 |
Conclusions: These 48 week data demonstrate that patients who switch from a TDF-based regimen to E/C/F/TAF maintain high efficacy, have statistically significant increases in BMD and have statistically significant improvements in multiple tests of renal function, as compared with patients remaining on their prior TDF-based regimen.
T. Mills1, J. Andrade2, G. DiPerri3, J. Van Lunzen4, E. Koenig5, R. Elion6, M. Cavassini7, J. Valdez Madruga8, J. Brunetta9, D. Shamblaw10, E. DeJesus11, C. Cohen12, A. Plummer13, Y. Liu13, S. McCallister13
1Anthony Mills MD, Inc., Los Angeles, United States, 2Hospital Civil de Guadalajara, Guadalajara, Mexico, 3University Hospital Amedeo De Savoia, Turin, Italy, 4Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany, 5Instituto Dominicano de Estudios Virologicos IDEZ, Santo Domingo, Dominican Republic, 6Whitman-Walker Health, Washington, United States, 7Centre Hospitalier Universitaire Valdois, Lausanne, Switzerland, 8Centro de Referencia e Treinamento Em DST/AIDS, Sao Paolo, Brazil, 9Maple Leaf Research, Toronto, Canada, 10La Playa Medical Group, San Diego, United States, 11Orlando Immunology Center, Orlando, United States, 12Community Research Initiative of New England, Boston, United States, 13Gilead Sciences, Foster City, United States