alafenamid

Alafenamide, in the pharmaceutical context often referred to as tenofovir alafenamide (TAF), is a nucleotide reverse transcriptase inhibitor prodrug used in antiretroviral therapy. It is designed to deliver tenofovir more efficiently to target cells while reducing exposure in the bloodstream compared with older prodrugs such as tenofovir disoproxil fumarate (TDF).

Activation and mechanism of action: After oral administration, alafenamide is preferentially activated inside cells, principally by enzymes such as cathepsin A, to release the active compound tenofovir. Tenofovir is then phosphorylated intracellularly to its active diphosphate form, which inhibits HIV-1 reverse transcriptase and, in chronic hepatitis B infection, the analogous viral polymerase. This targeted activation allows lower systemic exposure to tenofovir.

Clinical use and formulations: Tenofovir alafenamide is marketed for hepatitis B as Vemlidy, a single-drug therapy. For HIV, it is used in several fixed-dose combinations, including Genvoya (TAF/FTC/elvitegravir/cobicistat), Odefsey (TAF/FTC/rilpivirine), and Descovy (TAF/FTC). These regimens are designed to retain antiviral efficacy while reducing the risk of renal and bone toxicity associated with TDF.

Pharmacokinetics and safety: Compared with TDF, TAF achieves similar or better intracellular antiviral activity with markedly lower plasma concentrations of tenofovir, translating into improved renal and bone safety profiles in many patients. Common adverse effects are generally mild and may include nausea, headache, and fatigue. As with all antiretrovirals, resistance can occur with prolonged unsuppressed replication, though TAF generally has a high barrier to resistance when used in appropriate regimens.

See also: tenofovir disoproxil fumarate, antiretroviral therapy, HIV treatment, hepatitis B treatment.