A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide

Abstract

HIV is a serious chronic medical condition. Significant improvements in antiretroviral therapy have led to a transformation in its management. No curative treatment is available for HIV, and lifelong therapy is required with a combination of agents to control viral replication and prevent complications. Some of the older agents are notorious for many side effects, making patient compliance difficult, which is critical to preventing HIV resistance. Tenofovir is one of the newer, more tolerable, nucleotide reverse transcriptase inhibitors on the market; is a mainstay of many antiretroviral therapy combinations; and is now available in 2 different formulations, tenofovir disoproxil fumarate (TDF) and, the more recent, tenofovir alafenamide (TAF). These 2 formulations have very different pharmacokinetics, which seem to affect their efficacy and safety. This manuscript provides insight into the history of TDF and TAF development, their unique pharmacokinetics and pharmacology, clinically important adverse effects, monitoring, interactions, resistance, review of clinical studies, and guideline recommendations and clinical applications for tenofovir’s various indications.

Targeted Immuno-Antiretroviral HIV Therapeutic Approach to Provide Dual Protection and Boosts Cellular Immunity: A Proof-of-Concept Study

“…To counter that, our strategy is to introduce internal protection against new infection or during re-activation of latently infected cells. To achieve this, we loaded the targeted NPs with common NRTI (i.e., TAF or T) and integrase inhibitor (i.e., DTG or D) [28][29][30]. The xfR5-D + T NPs upon endosomal uptake causes sustained release of loaded ARVs in cell cytoplasm due to polymeric degradation.…”

“…In fact, combination of nucleoside reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs)-based cART to treat HIV infection has become most common practice for last decade [28]. Recently, tenofovir alfanamide (TAF) has become a common NRTI component of various approved rstline HIV-1 treatments [29]. Among INSTIs, dolutegravir (DTG) is a second-generation HIV integrase inhibitor is among the most common ARV in consideration as cART regimen [30].…”

Advances in Nucleoside and Nucleotide Analogues in Tackling Human Immunodeficiency Virus and Hepatitis Virus Infections

“…Tenofovir is yet another prominent drug and its main unit, namely, 9‐(2‐phosphonyl‐methoxypropyly)adenine (PMPA) is an acyclic diester of adenosine monophosphate. Tenofovir is a nucleotide analogue of adenosine monophosphate, with notably lower bioavailability and membrane permeability in its native form [50] . To enhance the membrane permeability and oral bioavailability, tenofovir is marketed as two prodrugs, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) [51] .…”

An Overview of Human Immunodeficiency Virus-1 Antiretroviral Drugs: General Principles and Current Status

“…These drugs are mainly administered as precursors, which then enter the host cell and are phosphorylated to the nucleotide form in order to display activity as a drug [ 13 14 ]. So far, eight types of NRTIs have been developed; recently, tenofovir alafenamide (TAF), with improved pharmacological activity of tenofovir, was developed and used ( Table 1 ) [ 15 ]. These drugs commonly lack a 3-OH (hydroxyl group) on the deoxyribose moiety of the nucleoside, and thus demonstrate an action mechanism during viral DNA synthesis, which terminates viral DNA synthesis, by incorporating themselves into the growing DNA chain and blocking the 3′-5′ phosphodiester bond with the next incoming nucleotide ( Fig.…”