tenofovir

Tenofovir is a nucleotide reverse transcriptase inhibitor used to treat HIV-1 infection and chronic hepatitis B virus (HBV) infection. It is available as two prodrugs: tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). TDF has been widely used in HIV therapy and in pre-exposure prophylaxis (PrEP), while TAF is a newer formulation that delivers the active drug more efficiently to cells, resulting in lower circulating levels of tenofovir and potentially reduced kidney and bone toxicity.

Mechanism of action: Tenofovir is converted in cells to tenofovir diphosphate, an analog of deoxyadenosine triphosphate. It inhibits HIV reverse transcriptase and HBV polymerase, causing premature termination of viral DNA synthesis and suppression of viral replication.

Spectrum and uses: Tenofovir is active against HIV-1 and HBV. It has activity against certain HIV-2 infections and is used as part of combination antiretroviral therapy for HIV; for HBV, it suppresses viral replication in chronic infection. In PrEP, tenofovir-containing regimens are used to reduce the risk of HIV acquisition in high-risk individuals.

Pharmacokinetics and administration: Both prodrugs are administered orally. TAF provides higher intracellular levels of the active metabolite with lower systemic exposure to tenofovir than TDF, which can influence tolerability and safety profiles. Dosing is typically once daily when used for HIV or HBV, with regimens chosen based on infection, coformulations, and clinical guidelines.

Safety and monitoring: Common adverse effects include nausea, headache, and fatigue. Renal function and bone mineral density should be monitored due to potential nephrotoxicity and bone loss, particularly with TDF. Severe lactic acidosis and hepatotoxicity are rare but serious. Resistance can emerge with mutations in reverse transcriptase, such as M184V or K65R, especially with poor adherence.