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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor [EPC]
Tenofovir alafenamide is a potent nucleoside analog reverse transcriptase inhibitor (NRTI) used for the treatment of HIV-1 infection and chronic hepatitis B. It is a targeted prodrug designed to deliver the active metabolite more efficiently to infected cells.
Name
Tenofovir Alafenamide
Raw Name
TENOFOVIR ALAFENAMIDE FUMARATE
Category
Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor [EPC]
Salt Form
Fumarate
Drug Count
6
Variant Count
10
Last Verified
February 17, 2026
RxCUI
1747691, 1747697, 2590641, 2590643, 1858261, 1858267, 2049671, 2049677, 1741733, 1741739, 1999667, 1999673, 1721613, 1721619, 2584354, 2584356
UNII
G70B4ETF4S, FWF6Q91TZO, LW2E03M5PG, YO603Y8113, EL9943AG5J, 212WAX8KDD, 4L5MP1Y7W7, 4GDQ854U53
About Tenofovir Alafenamide
Tenofovir alafenamide is a potent nucleoside analog reverse transcriptase inhibitor (NRTI) used for the treatment of HIV-1 infection and chronic hepatitis B. It is a targeted prodrug designed to deliver the active metabolite more efficiently to infected cells.
Detailed information about Tenofovir Alafenamide
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Tenofovir Alafenamide.
Tenofovir alafenamide (TAF) is a sophisticated nucleoside analog reverse transcriptase inhibitor (NRTI) and a targeted prodrug of tenofovir. It is primarily indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease and, in combination with other antiretroviral agents, for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Tenofovir alafenamide belongs to a class of medications known as antivirals, specifically designed to inhibit the replication of viral genetic material.
Originally developed by Gilead Sciences, TAF was designed to improve upon the safety profile of its predecessor, tenofovir disoproxil fumarate (TDF). While TDF was highly effective, it was associated with systemic exposure to tenofovir that could lead to renal (kidney) toxicity and decreases in bone mineral density. Tenofovir alafenamide, by contrast, is more stable in the plasma and delivers the active drug directly into the target cells (hepatocytes for HBV and lymphoid cells for HIV). This targeted delivery allows for a much lower dose (typically 25 mg compared to TDF’s 300 mg) while achieving higher intracellular concentrations of the active metabolite and significantly lower systemic tenofovir levels. The FDA first approved TAF as part of the combination product Genvoya in November 2015, followed by the standalone brand Vemlidy for Hepatitis B in 2016.
To understand how Tenofovir Alafenamide works, one must look at the viral replication cycle. Both HIV and HBV rely on specific enzymes to copy their genetic code so they can spread to new cells. In HIV, this enzyme is called reverse transcriptase; in HBV, it is the HBV DNA polymerase. Tenofovir alafenamide is an inactive prodrug that enters the target cells via passive diffusion and specialized transporters like OATP1B1 and OATP1B3.
Once inside the cell, TAF is converted into tenofovir through a process called hydrolysis, primarily mediated by an enzyme called cathepsin A in lymphoid cells or carboxylesterase 1 (CES1) in the liver. This tenofovir is then further modified by the cell’s own enzymes (phosphorylated) into its active form: tenofovir diphosphate. This active molecule is a 'mimic' or analog of the natural building blocks of DNA. When the virus tries to build new DNA, it mistakenly incorporates tenofovir diphosphate into the growing DNA chain. Because tenofovir diphosphate lacks a specific chemical group (the 3'-OH group) necessary for the next building block to attach, the DNA chain is terminated. This effectively halts the virus's ability to replicate and infect more cells.
Following oral administration, Tenofovir alafenamide is rapidly absorbed. Peak plasma concentrations (Tmax) are typically reached within 1 hour of dosing. When taken with a high-fat meal, the systemic exposure (AUC) of TAF increases by approximately 65% to 75%, though for many formulations, it can be taken with or without food depending on the specific co-formulated product.
TAF has relatively low plasma protein binding (less than 80%), but its active metabolite, tenofovir diphosphate, is highly concentrated within the target cells. The distribution into the central nervous system (across the blood-brain barrier) is limited for the parent drug, but the intracellular concentrations in peripheral blood mononuclear cells (PBMCs) are significantly higher than those achieved with older tenofovir formulations.
Unlike many drugs that are processed by the liver's cytochrome P450 system, TAF is primarily metabolized by intracellular hydrolases. Cathepsin A is the major enzyme responsible for its conversion in PBMCs, while CES1 is the primary enzyme in hepatocytes. Only a small fraction of TAF is metabolized by CYP3A4.
TAF is primarily eliminated via the feces (approximately 31%) and urine (less than 1%). The median terminal half-life of TAF in the plasma is very short (about 0.5 hours), but the intracellular half-life of the active tenofovir diphosphate is long (approximately 150 to 180 hours), which allows for once-daily dosing.
Tenofovir alafenamide is FDA-approved for two primary clinical indications:
Tenofovir alafenamide is available in several oral tablet forms:
> Important: Only your healthcare provider can determine if Tenofovir Alafenamide is right for your specific condition. Do not start or stop this medication without professional medical advice.
The standard dosage of Tenofovir Alafenamide varies depending on the condition being treated and the specific formulation used.
Tenofovir Alafenamide is approved for pediatric use in specific populations:
One of the primary advantages of TAF is its safety profile in patients with mild to moderate renal impairment.
Clinical studies did not include sufficient numbers of patients aged 65 and over to determine if they respond differently than younger patients. However, no specific dose adjustment is generally required unless significant renal impairment is present.
If you miss a dose, take it as soon as you remember, provided it is within the same day. If it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not 'double up' or take two doses at once to make up for a missed one. Frequent missed doses can lead to the virus becoming resistant to the medication.
In the event of an overdose, contact your local poison control center or seek emergency medical attention immediately. Symptoms of a significant overdose are not well-documented but may include severe gastrointestinal distress or an exacerbation of common side effects. Management typically involves supportive care and monitoring of vital signs.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as stopping treatment can lead to a severe 'flare-up' of Hepatitis B.
Most patients tolerate Tenofovir Alafenamide well, but some may experience mild to moderate side effects during the first few weeks of treatment as the body adjusts.
> Warning: Stop taking Tenofovir Alafenamide and call your doctor immediately if you experience any of the following symptoms, as they may indicate life-threatening conditions.
Tenofovir Alafenamide carries a Black Box Warning regarding the risk of Post-Treatment Severe Acute Exacerbation of Hepatitis B.
Discontinuation of anti-HBV therapy, including TAF, has been associated with severe acute exacerbations of hepatitis B, characterized by dramatic rises in serum ALT levels and potentially fatal liver failure. Patients who discontinue TAF should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
Report any unusual symptoms or persistent side effects to your healthcare provider immediately to ensure safe and effective treatment.
Tenofovir Alafenamide is a potent antiviral medication that requires careful medical supervision. It is not a cure for HIV-1 or HBV infection, and patients can still transmit these viruses to others through blood or sexual contact, although effective viral suppression significantly reduces the risk. Patients must continue to practice safe sex and avoid sharing needles.
The FDA has issued a Black Box Warning for Tenofovir Alafenamide regarding the Exacerbation of Hepatitis B. All patients should be tested for the presence of chronic Hepatitis B virus (HBV) before initiating treatment for HIV-1. In patients with 'co-infection' (both HIV and HBV), stopping TAF can lead to a severe, life-threatening spike in HBV activity. If TAF is discontinued, liver function must be monitored closely for several months through regular blood tests.
Though rare, lactic acidosis (too much acid in the blood) and severe liver enlargement with fat (steatosis) have been reported with the use of nucleoside analogs. This condition is a medical emergency and is more common in women, obese patients, and those who have been on antiretroviral therapy for a long time.
Tenofovir alafenamide is primarily excreted by the kidneys. While it is designed to be less toxic to the kidneys than older forms of tenofovir, cases of renal impairment, including acute renal failure and Fanconi syndrome, have been reported. Your doctor will monitor your estimated glomerular filtration rate (eGFR) and urine protein levels before and during treatment.
Clinical trials have shown slight decreases in bone mineral density (BMD) in patients taking TAF. Patients with a history of bone fracture or those at risk for osteoporosis should be monitored closely. Calcium and Vitamin D supplementation may be recommended by your healthcare provider.
In HIV-infected patients, the initiation of combination antiretroviral therapy may trigger an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, or tuberculosis), which may require further evaluation and treatment.
Regular laboratory testing is essential for anyone taking Tenofovir Alafenamide. These tests typically include:
Tenofovir alafenamide is not known to significantly affect the ability to drive or operate heavy machinery. However, if you experience dizziness or fatigue as a side effect, you should avoid these activities until you know how the medication affects you.
There is no direct drug-alcohol interaction with TAF. However, chronic alcohol consumption can damage the liver and kidneys, which are the primary organs involved in the processing and excretion of this drug. Patients with Hepatitis B should generally avoid alcohol as it accelerates liver damage (cirrhosis).
Never stop taking Tenofovir Alafenamide without consulting your doctor. Abrupt discontinuation can lead to viral resistance (in HIV) or a severe hepatitis flare (in HBV). If the drug must be stopped, your doctor will provide a specific monitoring plan to ensure your safety.
> Important: Discuss all your medical conditions, especially any history of kidney or liver disease, with your healthcare provider before starting Tenofovir Alafenamide.
Tenofovir alafenamide should not be used with certain drugs because they can significantly decrease TAF levels in the blood, leading to a loss of therapeutic effect and the development of viral resistance.
Tenofovir alafenamide does not typically interfere with common laboratory tests, but it can cause changes in the results of liver function tests, serum amylase, and lipid profiles. Always inform the laboratory staff and your doctor that you are taking an NRTI.
Most interactions with TAF occur through the modulation of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). These are 'efflux' transporters that pump drugs out of the gut or into the bile. Drugs that 'induce' (speed up) these pumps will lower TAF levels, while drugs that 'inhibit' (slow down) these pumps will increase TAF levels.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter drugs and vitamins.
Tenofovir Alafenamide is strictly contraindicated in the following scenarios:
These are conditions where the drug should be used only if the benefits outweigh the risks, and under very close supervision:
Patients who have experienced a mild rash with tenofovir disoproxil fumarate (TDF) may be able to take TAF, but they should be monitored closely. However, if a patient had a severe, systemic allergic reaction to any form of tenofovir, they should not be challenged with TAF.
> Important: Your healthcare provider will evaluate your complete medical history, including all prior drug allergies and your current kidney/liver status, before prescribing Tenofovir Alafenamide.
Tenofovir alafenamide is generally considered a preferred or acceptable option during pregnancy for both HIV and HBV.
Clinical trials of TAF did not include enough subjects aged 65 and over to determine if they respond differently. In general, elderly patients have a higher frequency of decreased renal function and other co-morbidities. Monitoring of renal function is especially important in this age group, and the risk of polypharmacy (drug interactions) is significantly higher.
TAF is a preferred tenofovir formulation for patients with mild to moderate renal impairment.
No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh A). However, the drug is not recommended for those with moderate to severe hepatic impairment (Child-Pugh B or C), as the pharmacokinetics and safety in these patients have not been sufficiently characterized.
> Important: Special populations require individualized medical assessment and frequent monitoring to ensure the safety of both the patient and, in the case of pregnancy, the developing fetus.
Tenofovir alafenamide (TAF) is an intracellular prodrug of tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog. TAF enters target cells, such as peripheral blood mononuclear cells (PBMCs) and hepatocytes, where it is hydrolyzed to tenofovir by intracellular enzymes like cathepsin A and carboxylesterase 1. Tenofovir is subsequently phosphorylated by cellular kinases to the active metabolite, tenofovir diphosphate.
Tenofovir diphosphate inhibits HIV-1 reverse transcriptase and HBV DNA polymerase by competing with the natural substrate deoxyadenosine 5'-triphosphate. Once incorporated into the viral DNA chain, it causes DNA chain termination because it lacks the 3'-hydroxyl group required for further 5' to 3' phosphodiester bond formation. TAF is highly specific for viral polymerases and has a low affinity for human DNA polymerases α, β, and mitochondrial DNA polymerase γ.
The pharmacodynamic effect of TAF is measured by the reduction in viral RNA (for HIV) or viral DNA (for HBV) in the plasma. TAF exhibits a potent dose-response relationship. Because TAF achieves higher intracellular concentrations than TDF, it can be administered at a much lower dose (25 mg vs 300 mg) while maintaining superior or non-inferior antiviral efficacy. There is no evidence of QT interval prolongation at therapeutic doses.
| Parameter | Value |
|---|---|
| Bioavailability | Not precisely determined in humans (prodrug) |
| Protein Binding | ~80% (TAF); <0.7% (Tenofovir) |
| Half-life | 0.5 hours (Plasma TAF); 150-180 hours (Intracellular TFV-DP) |
| Tmax | 1 hour |
| Metabolism | Cathepsin A (PBMCs); CES1 (Hepatocytes); CYP3A4 (minor) |
| Excretion | Fecal 31.7%, Renal <1% |
Tenofovir alafenamide is classified as a Nucleoside Reverse Transcriptase Inhibitor (NRTI). Within the NRTI class, it is a nucleotide analog, meaning it already contains a phosphate group (as a phosphonate), bypassing the first step of intracellular phosphorylation required by other NRTIs like zidovudine or abacavir.
Medications containing this ingredient
Common questions about Tenofovir Alafenamide
Tenofovir alafenamide (TAF) is an antiviral medication primarily used to treat two chronic viral infections: Human Immunodeficiency Virus type 1 (HIV-1) and Chronic Hepatitis B Virus (HBV). For HIV, it is always used as part of a multi-drug combination regimen to prevent the virus from replicating and to protect the immune system. For Hepatitis B, it can be used as a standalone treatment (Vemlidy) to reduce the amount of virus in the body and improve liver health. It works by blocking the enzymes the viruses need to copy their DNA, effectively halting their spread. TAF is preferred over older versions of tenofovir because it is more efficient at reaching target cells, allowing for lower doses and fewer systemic side effects.
The most frequently reported side effect of Tenofovir Alafenamide is headache, which affects more than 10% of patients but is usually mild. Other common side effects include gastrointestinal issues such as nausea, abdominal pain, and diarrhea, as well as a general feeling of fatigue or tiredness. In patients being treated for Hepatitis B, back pain and a mild cough are also occasionally reported. Most of these symptoms are transient and tend to resolve as the body becomes accustomed to the medication. However, if these side effects persist or become severe, it is important to discuss them with your healthcare provider to ensure they are not signs of a more serious reaction.
While there is no known direct chemical interaction between alcohol and Tenofovir Alafenamide, it is generally advised to limit or avoid alcohol consumption, especially if you are being treated for Hepatitis B. Alcohol places significant stress on the liver and can accelerate the progression of liver disease, cirrhosis, and liver cancer, which the medication is intended to prevent. Furthermore, both alcohol and TAF are processed by the body's filtration systems, and excessive drinking could complicate the monitoring of your liver and kidney function. If you have HIV, alcohol can also interfere with your ability to stick to a strict daily dosing schedule, which is vital for preventing drug resistance. Always consult your doctor about what level of alcohol consumption, if any, is safe for your specific health situation.
Tenofovir Alafenamide is generally considered a safe and effective option for pregnant women who require treatment for HIV or Hepatitis B. Extensive data from the Antiretroviral Pregnancy Registry have not shown an increased risk of major birth defects compared to the general population. For women with HIV, taking TAF as part of a combination regimen is essential to reduce the risk of transmitting the virus to the baby. For women with Hepatitis B, TAF may be used to lower the viral load in the mother's blood, further protecting the infant during delivery. Because every pregnancy is unique, it is vital to work closely with an infectious disease specialist or an obstetrician experienced in managing viral infections during pregnancy.
Tenofovir Alafenamide begins working at the molecular level within hours of the first dose, as it rapidly enters cells and begins inhibiting viral replication. However, the 'clinical' effect—measured by a decrease in the amount of virus in your blood (viral load)—is usually observed over several weeks to months. In patients with HIV, the goal is to reach an 'undetectable' viral load, which typically takes 3 to 6 months of consistent daily use. For Hepatitis B, it may take several months to see a significant reduction in HBV DNA and an improvement in liver enzyme levels (ALT). Consistent, daily adherence is the most important factor in how quickly and effectively the medication works.
No, you should never stop taking Tenofovir Alafenamide suddenly without a direct instruction from your healthcare provider. For patients with Hepatitis B, stopping the medication can cause a 'severe acute exacerbation,' where the virus rebounds aggressively and causes rapid, life-threatening liver damage. For patients with HIV, stopping the drug allows the virus to begin replicating again, which can lead to the development of drug resistance, making the virus much harder to treat in the future. If you must stop the medication due to side effects or other reasons, your doctor will need to monitor your blood work very closely for several months to ensure your safety.
If you miss a dose of Tenofovir Alafenamide, take it as soon as you remember on the same day. If you do not remember until the following day, skip the missed dose entirely and take your next dose at the regularly scheduled time. Do not take two doses at once to 'catch up,' as this can increase the risk of side effects without providing extra benefit. To ensure the medication remains effective and to prevent the virus from developing resistance, try to take your dose at the same time every day. Using a pillbox, a smartphone alarm, or a treatment-tracking app can be very helpful in maintaining a consistent routine.
Recent clinical studies and real-world data have indicated that some patients experience weight gain after starting Tenofovir Alafenamide, particularly when it is used as part of an HIV treatment regimen that also includes an integrase inhibitor. The reasons for this weight gain are not fully understood but may be related to the drug's metabolic profile or a 'return to health' effect after the virus is controlled. The amount of weight gain varies significantly between individuals and may be influenced by diet, exercise, and genetics. If you are concerned about changes in your weight or body shape while taking TAF, discuss these changes with your doctor, who can help you manage your metabolic health through lifestyle adjustments or medication changes.
Tenofovir Alafenamide can be taken with many other medications, but it does have several important drug interactions. It should not be taken with strong P-gp inducers like the antibiotic rifampin or the herbal supplement St. John's Wort, as these will make TAF much less effective. It also interacts with certain anti-seizure medications and some other antivirals. Because TAF is often part of a combination pill for HIV, the other drugs in that pill may have their own set of interactions. Always provide your doctor and pharmacist with a complete list of all prescription drugs, over-the-counter medicines, vitamins, and herbal supplements you are taking to avoid potentially dangerous interactions.
As of 2024 and looking toward 2026, Tenofovir Alafenamide (Vemlidy) and its common combination forms (like Descovy and Biktarvy) are still under patent protection in many countries, including the United States. This means that low-cost generic versions may not be widely available in these markets yet. However, generic versions are produced and distributed in many low- and middle-income countries through licensing agreements to ensure global access to essential HIV and HBV treatments. Patients in the U.S. who have difficulty affording the medication may be eligible for patient assistance programs or co-pay cards provided by the manufacturer. Always check with your pharmacist or insurance provider for the most current information on drug costs and generic availability.