Tenofovir

Table of contents

• What is tenofovir?
• How does tenofovir work?
• Which conditions is tenofovir used or studied for?
• How is tenofovir given?
• What do the clinical trials show?
• What side effects are known?

What is tenofovir?

Tenofovir is a nucleotide analog reverse transcriptase inhibitor, a class of antiviral medicines that block an enzyme the human immunodeficiency virus (HIV) and hepatitis B virus (HBV) need to multiply.^[3] The full name used in the registry is tenofovir disoproxil, and it is most often given as tenofovir disoproxil fumarate.^[3] Tenofovir disoproxil is an authorised medicine, and in the trial records it appears as part of a fixed combination product together with emtricitabine.^[1][2] The product name listed in the registry is Tenofovir disoproxil and emtricitabine.^[1]

How does tenofovir work?

Tenofovir disoproxil fumarate is described in the prescribing information as a nucleotide analog HIV-1 reverse transcriptase inhibitor and an HBV reverse transcriptase inhibitor.^[3] Reverse transcriptase is an enzyme that HIV and hepatitis B virus use to copy their genetic material inside human cells. By blocking this enzyme, tenofovir stops the virus from multiplying.^[3]

Which conditions is tenofovir used or studied for?

• HIV-1 infection — tenofovir disoproxil fumarate is authorised for treating HIV-1 infection in adults and paediatric patients 2 years of age and older, in combination with other antiretroviral agents.^[3]
• Chronic hepatitis B — tenofovir disoproxil fumarate is authorised for treating chronic hepatitis B in adults and paediatric patients 12 years of age and older.^[3]
• HIV-1 prevention — in a Phase 3 trial, tenofovir disoproxil and emtricitabine are given daily as the comparison arm for preventing HIV-1 infection.^[1]
• Pre-exposure prophylaxis (PrEP) users with sexually transmitted infections — a Phase 3 trial includes tenofovir-containing regimens in people using PrEP and people living with HIV.^[2]

How is tenofovir given?

Tenofovir disoproxil fumarate is a film-coated tablet taken by mouth.^[3] The registry lists the route of administration as oral use.^[1] In the trials, tenofovir disoproxil and emtricitabine are given as a fixed combination tablet, with doses of 445 mg or 200 mg tenofovir disoproxil in the records.^[1][2] The prescribing information gives a recommended adult dose of 300 mg once daily for HIV-1 or chronic hepatitis B.^[3]

What do the clinical trials show?

The registry data contain two Phase 3 trials in which tenofovir disoproxil and emtricitabine appear as an intervention. Both trials are currently authorised.

Which conditions are studied in these trials?

One trial, MK-8527-011, studies HIV-1 prevention.^[1] It compares a new monthly oral medicine, MK-8527, against daily tenofovir disoproxil and emtricitabine for preventing HIV-1 infection.^[1] The other trial, MiDoxyR-PEP, studies bacterial resistance and gut microbiota in people using pre-exposure prophylaxis (PrEP) and people living with HIV who have sexually transmitted infections.^[2]

What phases and status do the trials have?

Both trials are Phase 3 studies, meaning they test the interventions in large groups of people.^[1][2] Their status is listed as authorised, which means they have received regulatory approval to begin.^[1][2]

What are the trials measuring?

MK-8527-011 measures the number of participants with adjudicated HIV-1 infection, the number who experience at least one adverse event, and the number who discontinue study intervention due to an adverse event.^[1] MiDoxyR-PEP measures the prevalence of nasal colonisation by doxycycline-resistant Staphylococcus aureus strains.^[2]

Who can take part in these trials?

MK-8527-011 plans to enrol 4,700 participants.^[1] The trial record does not list detailed eligibility criteria beyond the condition studied. MiDoxyR-PEP plans to enrol 392 participants, specifically men who have sex with men (MSM) and transgender women.^[2]

What side effects are known?

The prescribing information carries a boxed warning about severe acute exacerbations of hepatitis in hepatitis B patients who stop taking tenofovir disoproxil fumarate.^[3] Hepatic function should be monitored closely in these patients after discontinuation.^[3] The risk management plan summary describes important risks of tenofovir disoproxil tablets and notes that the summary of product characteristics and package leaflet give essential safety information to healthcare professionals and patients.^[4]