Tenofovir (also tenofovirdisoproxil) is used therapeutically for HIV-1 and hepatitis B infections. Tenofovirdisoproxil is thereby activated in human cells to tenofovir. On the one hand, it inhibits reverse transcriptase in HIV viruses (or DNA polymerase in hepatitis B viruses), and on the other hand, it is incorporated into the viral DNA as a false building block, so that the virus can no longer replicate. It is generally well tolerated, but can lead to kidney failure if there is pre-existing kidney damage.
What is tenofovir?
Tenofovir is an antiviral drug (antiviral) and belongs to the group of nucleoside reverse transcriptase inhibitors (NRTIs) in HIV. The drug can also block DNA polymerase in hepatitis B viruses. It is a modified adenosine monophosphate analog and consists of a pentose, a nucleic base, and a phosphoric acid residue. Tenofovirdisoproxil is the prodrug in this case, which is activated by the body’s own enzymes to form tenofovir.
Pharmacologic action
The drug is taken in tablet form and should be taken with meals. The correct dosage should be discussed with the treating physician and strictly adhered to, otherwise resistance may develop. There is low plasma protein binding and the plasma half-life is 12 to 18 hours. Excretion is mainly via the kidney. The active ingredient tenofovirdisoproxil is absorbed unchanged into the human cell and is phosphorylated into nucleotide triphosphates and activated by special enzymes called kinases. Tenofovir has a dual mechanism of action. On the one hand, the activated derivatives inhibit the viral reverse transcriptase in the case of HIV and the DNA polymerase in the case of hepatitis B. On the other hand, they are also incorporated into the human cell. On the other hand, they are also incorporated into the viral DNA as a false building block. Consequently, DNA synthesis is now aborted due to the missing 3`hydroxyl group on the activated Tenofovir. As a result, the virus cannot reproduce any further. However, there are also DNA polymerases in the human body, especially in the mitochondria. These can also be inhibited by the drug, with corresponding side effects.
Medical application and use
Tenofovir is used in the treatment of HIV-1 and hepatitis B infection. Initially, the drug was approved for HIV therapy in Europe in 2002, and since 2008, it has been indicated for the treatment of chronic hepatitis B. In particular, tenofovir is used in patients with hepatitis B and active viral replication and elevated liver enzymes. In the treatment of HIV, tenofovir is always used in combination with other drugs. The therapy can be used in adults as well as in adolescents aged 12 to 18 years. In pregnant women with chronic hepatitis B infection, tenofovir can reduce transmission of the virus to the unborn child. Here, under study conditions, the drug was given in the last trimester of pregnancy and administration continued until 4 weeks after birth. A significant increase in malformations in the unborn child was not observed until then. It should be noted that treatment with tenofovir does not result in a cure of HIV-1 or hepatitis B, so that the patient can still transmit viruses to other people even during therapy. Appropriate protective measures are therefore essential to avoid infection.
Risks and side effects
In general, tenofovir is very well tolerated. Common side effects include nausea, diarrhea, fatigue, dizziness, and headache. However, caution is advised in patients with existing renal impairment. The drug has a nephrotoxic effect and in rare cases can lead to kidney failure. Tenofovir should also not be taken with other medications that may cause additional damage to the kidney. Tenofovir is contraindicated in patients requiring dialysis. Inhibition of human mitochondrial DNA polymerase may result in some rare but important long-term side effects. In particular, infants who have been exposed to nucleoside therapy in utero may be at increased risk for side effects. There may be, due to an excess of lactic acid in the blood, lactic acidosis. This manifests as deep and rapid breathing, drowsiness, and nausea, vomiting, and stomach pain. This should be attended to immediately by a physician, as this side effect can be fatal.Furthermore, inflammation of the pancreas (pancreatitis) may occur, which is particularly noticeable as pain in the upper abdomen. In rare cases, muscle and joint weakness, damage to the nerve pathways (polyneuropathy) and lipodystrophy (body fat redistribution disorder) may occur. If there is a known allergic reaction to tenofovir itself or to other components of the drug, it should not be taken. Pregnancy presents a special challenge and requires individualized medication management. Breastfeeding during therapy is not permitted because it is as yet unknown whether the drug passes into breast milk.
