Tenofovir is an antiviral medication used to treat two major infections: HIV and chronic hepatitis B. It works by blocking the enzyme that both viruses need to copy their genetic material, stopping viral replication in its tracks. Tenofovir is also a cornerstone of HIV prevention, where it reduces the risk of getting HIV from sex by about 99% when taken as prescribed.
How Tenofovir Works
Both HIV and hepatitis B rely on an enzyme called reverse transcriptase to build new copies of their DNA inside your cells. Tenofovir mimics one of the natural building blocks of DNA. When the virus tries to use it during replication, tenofovir gets incorporated into the growing DNA chain and acts like a dead end, terminating the chain so no more DNA can be built. This halts the virus’s ability to multiply.
Because tenofovir targets a mechanism shared by both HIV and hepatitis B, a single drug can be effective against two very different infections. For HIV, it’s always used alongside other antiretroviral medications. For hepatitis B, it can be used on its own.
Treating HIV
Tenofovir is one of the most widely prescribed components of HIV treatment worldwide. It’s FDA-approved for adults and children aged 2 and older who weigh at least 10 kg (about 22 pounds). It is never used alone for HIV. Instead, it’s combined with other antiretroviral drugs, often packaged into a single daily pill that contains two or three medications together.
The goal of HIV treatment is to suppress the virus to undetectable levels in the blood, which keeps the immune system healthy and prevents transmission to others. Tenofovir-based regimens are a first-line choice for achieving this. Most people start treatment with a combination pill that includes tenofovir plus one or two other antivirals, taken once daily.
Preventing HIV With PrEP
One of tenofovir’s most significant roles is in pre-exposure prophylaxis, or PrEP. This means taking the medication before potential exposure to HIV to prevent infection. According to the CDC, PrEP reduces the risk of getting HIV from sex by about 99% when taken as prescribed. For people who inject drugs, PrEP pills reduce the risk by at least 74%.
PrEP typically involves taking a daily pill that combines tenofovir with another antiviral. It’s intended for people who are HIV-negative but at higher risk of infection, such as those with an HIV-positive partner or those who don’t consistently use condoms.
Treating Chronic Hepatitis B
Tenofovir is one of the preferred first-line treatments for chronic hepatitis B in both adults and children. The American Association for the Study of Liver Diseases (AASLD) recommends it as an initial therapy for adults with active chronic hepatitis B, alongside two other options.
The drug is particularly effective at driving hepatitis B viral levels down to nearly undetectable. After two to three years of continuous treatment, about 76% of patients who initially test positive for a specific viral protein (HBeAg-positive) achieve deep viral suppression. That number climbs to 93% for HBeAg-negative patients. Tenofovir is also preferred because the hepatitis B virus rarely develops resistance to it, unlike some older antiviral options.
For people with hepatitis B who have advanced liver scarring (cirrhosis), tenofovir is especially important. Guidelines recommend antiviral therapy to reduce the risk of the liver deteriorating further, and tenofovir is a preferred choice because of its potency and minimal resistance risk. People with decompensated cirrhosis, where the liver is significantly impaired, typically need to stay on antiviral therapy indefinitely.
Two Formulations: TDF and TAF
Tenofovir comes in two different formulations that deliver the same active drug but behave differently in the body. The older version, tenofovir disoproxil fumarate (TDF), has been available since the early 2000s. The newer version, tenofovir alafenamide (TAF), was designed to be gentler on the kidneys and bones.
The key difference is how much tenofovir ends up in the bloodstream versus inside the cells where it’s actually needed. TAF delivers 6.5 times more of the active drug into cells while producing 91% lower levels in the blood. A 25 mg dose of TAF achieves the same effect as a 300 mg dose of TDF. Because high blood levels of tenofovir are what drive kidney and bone side effects, this pharmacological difference has real clinical consequences.
Kidney and Bone Safety
The most important safety concern with tenofovir, particularly the older TDF formulation, involves the kidneys and bones. TDF can cause kidney tubule damage and, in rare cases, a condition called Fanconi syndrome where the kidneys leak essential minerals into the urine. It can also reduce bone mineral density over time.
A pooled analysis of 26 clinical trials showed clear differences between the two formulations. Among more than 6,300 people taking TAF, there were zero cases of kidney tubule damage, compared with 10 cases among roughly 3,000 people on TDF. Only 0.05% of TAF users had to stop the medication due to kidney problems, versus 0.47% of TDF users. Kidney function markers also told a consistent story: people on TAF maintained more stable kidney filtration rates, had less protein leaking into their urine, and showed improvements in multiple biomarkers of kidney tubule health that worsened on TDF.
Overall kidney-related side effects through 96 weeks were reported in 5.4% of TAF users compared to 8.5% of TDF users in studies of people starting treatment for the first time. For people already on TDF who switched to TAF, kidney function markers actually improved after the switch.
Drug Interactions to Be Aware Of
Tenofovir interacts with several other medications, and the specific concerns differ between TDF and TAF. The most important rule is to avoid combining TDF with other drugs that can harm the kidneys. This includes certain hepatitis treatments, some seizure medications, and the antiviral cidofovir. When a potentially kidney-stressing combination is necessary, switching from TDF to TAF may be a safer alternative.
TAF, on the other hand, is sensitive to drugs that speed up its breakdown in the body. Medications like rifampin (used for tuberculosis), the seizure drugs carbamazepine and phenytoin, and the herbal supplement St. John’s wort can all reduce TAF levels enough to compromise its effectiveness. These interactions don’t affect TDF, so in situations involving tuberculosis treatment, for example, TDF may be the better choice.
Use in Children
Tenofovir (TDF) is approved for children aged 2 and older who weigh at least 10 kg, for both HIV and hepatitis B. It has not been approved for infants under 2. Dosing in children is weight-based, scaling up gradually. Children and adolescents who weigh 35 kg or more receive the standard adult dose. Several combination pills that include tenofovir are also approved for adolescents, though each has its own minimum weight and age requirements.
Resistance
Like all antivirals, tenofovir can lose effectiveness if the virus mutates. The primary resistance mutation for HIV is called K65R, a change in the reverse transcriptase enzyme that makes it harder for tenofovir to get incorporated into viral DNA. In one study of people whose treatment regimen was failing, 12% had this mutation detectable by standard testing, with additional cases found using more sensitive methods. Resistance is more likely to emerge when the virus isn’t fully suppressed, which is why consistent daily dosing and using tenofovir in combination with other drugs are both critical. For hepatitis B, tenofovir resistance is extremely rare, which is one of the reasons it remains a preferred long-term treatment.