by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
December 15, 2020
Pilkington, V. et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated meta-analysis of 14,894 patients across 14 trials. AIDS 2020, 34:2259–2268
Tenofovir disoproxil fumarate (TDF) along with the newer formulation tenofovir alafenamide (TAF) are both highly effective treatments for HIV. There are concerns regarding the impact of TDF on bone mineral density and risk of nephrotoxicity. TAF produces higher intracellular concentrations but is thought safer due to lower plasma concentrations of tenofovir. In addition, when ritonavir or cobicistat are used as part of an ART regimen, they increase the concentration of TDF. This study is an update of a prior systematic review of 14 clinical trials looking at efficacy and safety of TDF vs TAF when used with and without boosted co-formulations. Differences in efficacy were based specifically on viral suppression. Safety endpoints included grades 3–4 adverse events and related drug discontinuation. Lastly, specific markers of bone and renal function were assessed. There was a statistically significant difference in efficacy seen in the boosted subgroup in favor of TAF but the difference was small (94% vs. 92% HIV RNA < 50 copies/mL) and there was no difference in the unboosted subgroup (89% vs 90% < 50 copies/mL). For renal outcome there was no difference in renal tubular events between patients taking TAF and TDF or the number of discontinuations due to renal adverse events. Overall, there were no significant differences between TAF and TDF for any of the key safety endpoints analyzed which included both bone markers and renal tubular events.
Author’s Commentary:
These studies included almost 15,000 patients with about 24,000 patient-years of follow up. Across all main safety endpoints, no significant differences between TAF and TDF were seen. Although there were some differences in patients on boosted regimens, these are now less commonly used with the majority of patients now taking INSTIs. Regarding the concern for renal tubular events, there were only 3 across these studies and the overall risk difference was 0%. Another point of this TDF vs TAF discussion should include lipid abnormalities and weight gain seen with TAF. For the majority of patients who need tenofovir as part of their ART regimen or for PrEP these data support TDF as a safe, effective, and more affordable option. Generic “Truvada” (tenofovir disoproxil fumarate/emtricitabine) became available in the U.S. in October although the current retail price is about $1500 which is not significantly lower than the branded formulation.
The author has no conflicts of interest to disclose.
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