Latest research on Tenofovir

Tenofovir disoproxil fumarate (a prodrug of tenofovir), marketed by Gilead Sciences under the trade name Viread®, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. [Wikipedia] In vivo tenofovir disoproxil fumarate is converted to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.

Latest findings

These guidelines recommended a preferred first-line treatment with a combination of Tenofovir disoproxil fumarate (TDF), Lamivudine (3TC) or Emtricitabine (FTC) and Efavirenz (EFV), with second-line treatment using two nucleoside analogues and a boosted protease inhibitor (PI) [1]. [source, 2016]
TAF is a prodrug of Tenofovir, which is boosted significantly by either Ritonavir or cobicistat. [source, 2016]
In one pharmacokinetic study, the mean intracellular concentrations of Tenofovir diphosphate were 6.5 times higher using TAF compared to TDF, whereas the mean plasma Tenofovir exposure was 91% lower [32]. [source, 2016]
This dosing is supported by a recently published pharmacokinetic study showing that the plasma concentration of Tenofovir was bioequivalent between TAF 10 mg once daily given with cobicistat and TAF 25 mg given without cobicistat [33]. [source, 2016]
Results from randomized trials and cohort studies have shown an increased risk of renal adverse events when TDF is used in combination with a ritonavir-boosted PI and when Tenofovir plasma concentrations are high [40–43]. [source, 2016]
Patients receiving TAF were more likely to show increases in LDL cholesterol and total cholesterol plasma levels, as Tenofovir tends to lower lipid levels. [source, 2016]
There may be no clinically significant safety advantage of TAF 25 mg once daily over Tenofovir 300 mg, in the absence of cobicistat or Ritonavir. [source, 2016]
Table 6 shows the key planned and ongoing clinical trials needed to establish new treatments – EFV 400 mg, dolutegravir and Tenofovir alafenamide – in future large-scale HIV treatment programmes. [source, 2016]
In addition, many antiretrovirals (e.g. rilpivirine, Efavirenz, Tenofovir, elvitegravir and boosted protease inhibitors) are ingested with specific recommendations for food intake, which may be problematic on commercial flights when meal times are fixed. [source, 2016]
Although MECs for NRTIs are not established, the pharmacokinetic parameters of the active intracellular metabolites of Tenofovir and Emtricitabine have been established in one tail study, where both were found to have long terminal half-lives of 164 and 39 h, respectively [21]. [source, 2016]