Genvoya TAF Regimen Works Well with Improved Bone and Kidney Safety at 96 Weeks

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The Genvoya single-tablet regimen containing tenofovir alafenamide (TAF) suppressed HIV as well as a similar coformulation containing the older tenofovir disoproxil fumarate (TDF), but demonstrated better bone and kidney tolerability after 2 years of treatment, according to a report in the May 1 edition of the Journal of Acquired Immune Deficiency Syndromes.

Gilead Sciences' TAF is a new pro-drug that delivers the active agent (tenofovir diphosphate) to HIV-infected cells more efficiently than the current TDF formulation (Viread, also in Truvada, Atripla, Complera, and Stribild). TDF is considered generally safe and well-tolerated, but it can cause bone loss soon after starting therapy and can lead to kidney problems in susceptible people. TAF produces high intracellular drug levels with a smaller dose than TDF, which means lower concentrations in the blood and less drug exposure for the kidneys, bones, and other organs and tissues.

David Wohl from the University of North Carolina at Chapel Hill and colleagues conducted a pair of Phase 3 studies doing a head-to-headcomparison of first-line HIV treatment using a TAF-based versus a TDF-based single-tablet regimen (GS-US-292-0104/NCT01780506and GS-US-292-0111/NCT01797445).

Together, these international clinical trialsenrolled 1733 previously untreated participants. About 85% were men and the median age was 34 years. The median baseline CD4 T-cell count was approximately 400 cells/mm3 and nearly a quarter had high viral load (>100,000 copies/mL). At baseline they had near-normal kidney function with an estimated glomerular filtration rate -- an indicator of creatinine clearance -- of at least 50 mL/min (median 116 mL/min).

Participants were randomly assigned to receive a once-daily single-tablet regimen containing 150 mg elvitegravir, 150 mg of the booster cobicistat, and 200 mg emtricitabine, with either 10 mg TAF (Stribild coformulation) or 300 mg TDF (Genvoya coformulation).

Results

"These longer-term data support [elvitegravir/cobicistat/emtricitabine/TAF] as a safe, well-tolerated, and durable regimen for initial HIV-1 treatment," the study authors concluded.

"Together, these longer-term safety data support the hypothesis that circulating levels of tenofovir are responsible for the bone and renal toxicity of TDF and that the markedly reduced tenofovir level delivered by TAF minimizes such exposure and is protective against renal and bone effects," they added in their discussion.

5/3/16

Reference

D Wohl, S Oka, N Clumeck, et al. Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results. Journal of Acquired Immune Deficiency Syndromes72(1):58-64. May 1, 2016.