Meta-analysis of TAF vs TDF in boosted vs unboosted regimens
Polly Clayden, HIV i-Base
Tenofovir disoproxil fumarate (TDF) boosted with ritonavir or cobicistat, led to higher risks of bone and renal adverse events, and lower rates of viral load suppression, compared with tenofovir alafenamide (TAF). But, unboosted, there were no differences between the two versions of tenofovir for efficacy and only slight differences in safety.
Results from a meta-analysis of TDF versus TAF, authored by Andrew Hill and colleagues, were presented at the Fourth Joint Conference of BHIVA/BASHH.
Boosting agents significantly increase plasma AUC concentrations of TDF (25–37%). Higher plasma tenofovir levels are associated with higher risks of renal and bone adverse events. The TAF dose is reduced from 25 to 10 mg daily when boosted but TDF remains at 300 mg daily. TDF is most commonly used worldwide in unboosted regimens, combined with 3TC and either efavirenz or dolutegravir.
Using a PUBMED/Embase search the authors found 11 randomised head-to-head trials of TDF vs TAF – including 8110 participants.
Nine trials compared TDF vs TAF in HIV positive people and two in people with hepatitis B. There were 4,574 participants who received boosting agents (with both TDF and TAF) representing 7,198 person years (p/y) follow up. The remaining 3,537 participants received unboosted regimens, giving 3,595 p/y follow up.
The authors noted that participants were largely young to middle aged, with no pre-existing osteoporosis or kidney damage.
The analysis revealed boosted TDF treated participants had marginally lower viral load suppression rates <50 copies/mL (p=0.05), more bone fractures (p=0.04), lower bone mineral density (p<0.001) and more discontinuation for bone (p=0.03) or renal (p=0.002) adverse events.
In contrast, there were no significant differences in viral load suppression rates or clinical safety endpoints (except bone mineral density) between unboosted TDF and TAF. (See Table 1).
Table 1: Meta-analysis of safety and efficacy TDF vs TAF
|Efficacy/safety||TDF vs TAF
|TDF vs TAF
|% with viral load <50 copies/mL||86 vs 90, (p=0.05)||Both 91%
|Grade 1–4 AEs||57 vs 55%, (p=NS)||72 vs 70%, (p=NS)|
|Grade 3–4 AEs||6 vs 5%, (p=NS)||4 vs 5%, (p=NS)|
|Bone fractures||1 vs 0, (p=0.04)||0 vs 1%, (p=NS)|
|D/C for bone AEs||1 vs 0, (p=0.03)||Both 0%, (p=NS)|
|D/C for renal AEs||1 vs 0, (p=0.002)||Both 0%, (p=NS)|
Key AE, adverse events; D/C, discontinue; NS, not significant
More details from this meta-analysis are included in the version recently published online in the Journal of Virus Eradication. 
The first generic TAF-containing fixed dose combination (FDC) was tentatively approved by the US FDA earlier in the year (dolutegravir/FTC/TAF).  The new FDC could offer several programmatic benefits to low- and middle-income countries where genetics are accessible including lower cost and smaller tablet size (easier to swallow, transport and store).
But evidence gaps, particularly for pregnancy and TB coinfection have meant that TAF is not yet included in WHO guidelines or Essential Medicines List.
In high-income countries (including in the UK), where generic versions of newer antiretrovirals are not available but generic TDF is or shortly will be, the significant difference in price will limit access to TAF to people with reduced renal and bone health.
In the UK, the list price for TAF/FTC is £4268 per year, which although discounted for bulk purchasing, is still considerably higher than Hill et al’s estimated £600 price for generic TDF/FTC. 
- Hill A et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety? 4th Joint BHIVA/BASHH Conference, 17 – 20 April 2018, Edinburgh. Poster abstract P27. HIV Medicine, 19 (Suppl. 2), s21–s152
- Hill A et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety. Journal of Virus Eradication 4: 73-80, 2018.
- Clayden P. FDA grants tentative approval to first DTG/FTC/TAF FDC. HTB. 21 February 2018.
- BNF. Emtricitabine with tenofovir alafenamide.