What is Tenofovir?
Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) antiretroviral medication used primarily for the treatment of HIV-1 infection and chronic hepatitis B virus (HBV) infection. 1
Formulations and Clinical Uses
Tenofovir is available in two main prodrug formulations, each with distinct pharmacological properties:
Tenofovir Disoproxil Fumarate (TDF)
- TDF is indicated in combination with other antiretroviral agents for treating HIV-1 infection in adults and pediatric patients 2 years of age and older. 1
- TDF is also approved for treating chronic hepatitis B in adults and pediatric patients 12 years of age and older. 1
- The standard dose is 300 mg once daily taken orally, without regard to food. 1
- TDF requires only 2 intracellular phosphorylation steps for activation (compared to 3 steps for nucleoside analogues), potentially producing more rapid conversion to its active metabolite. 2
Tenofovir Alafenamide (TAF)
- TAF allows better uptake by lymphoid tissue compared to TDF and is associated with fewer tenofovir-related adverse effects, particularly reduced nephrotoxicity and less bone mineral density loss. 3, 4
- TAF is available in combination regimens for HIV treatment and as monotherapy (Vemlidy®) for HBV treatment. 4
- TAF is not recommended in patients with creatinine clearance below 30 mL/min. 3
HIV Treatment Applications
As Part of Initial Antiretroviral Therapy (ART)
- Tenofovir-containing regimens (either TAF or TDF) combined with emtricitabine and an integrase strand transfer inhibitor (InSTI) are recommended as initial therapy for HIV-1 infection. 3
- Specific recommended combinations include dolutegravir plus TAF/emtricitabine or elvitegravir/cobicistat/TAF/emtricitabine. 3
- TAF-containing regimens and TDF-containing regimens have similar virological efficacy. 3
Efficacy Profile
- Tenofovir effectively reduces viral load in both treatment-naive and treatment-experienced patients with baseline NRTI resistance mutations. 5
- It produces sustained suppression of viral replication with a convenient once-daily dosing regimen. 5
- Tenofovir offers little or no risk for virus-drug resistance development. 4
HIV Prevention (Pre-Exposure Prophylaxis - PrEP)
TDF-Based PrEP
- Daily oral TDF/emtricitabine (Truvada®) is the recommended first-line PrEP regimen for men who have sex with men (MSM) at risk of HIV acquisition. 6
- A 1-week lead-in period is required before adequate tissue levels are achieved for rectal and penile exposures. 6
- Continue for 1 week after the last sexual exposure when discontinuing. 6
TAF-Based PrEP (Descovy®)
- Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) is specifically indicated for MSM and transgender women who have sex with men, particularly those with or at risk for kidney dysfunction, osteopenia, or osteoporosis. 7
- Critical limitation: Descovy is NOT currently recommended for cisgender women or prevention of HIV-1 infection from receptive vaginal sex. 7
- Descovy is also not recommended for on-demand or event-driven PrEP (the "2-1-1" dosing schedule). 7
Hepatitis B Treatment
- Tenofovir (both TDF and TAF formulations) effectively lowers HBV DNA levels and may improve liver condition in patients with chronic hepatitis B. 1
- TAF (Vemlidy®) has replaced TDF (Viread®) as the preferred formulation for HBV treatment due to improved safety profile. 4
- The optimal duration of treatment for chronic hepatitis B is unknown. 1
Important Safety Considerations and Monitoring
Renal Toxicity
- TDF should be avoided or dose-adjusted in patients with creatinine clearance below 60 mL/min. 3
- Do not prescribe TDF-based therapy if creatinine clearance is <60 mL/min. 6
- Monitoring for kidney disease with estimated glomerular filtration rate, urinalysis, and testing for glycosuria and albuminuria or proteinuria is recommended when therapy is initiated or changed and every 6 months once HIV RNA is stable. 3
- TAF demonstrates significantly lower risk of nephrotoxicity, with median eGFR decline of only -0.3 mL/min versus -5.0 mL/min with TDF at 96 weeks. 8
Bone Health
- TDF may cause osteopenia or osteoporosis. 3
- TAF is associated with less bone mineral density loss compared to TDF. 3, 4
- For patients with bone health concerns, TAF is preferred over TDF. 7, 6
Hepatitis B Flare Risk
- CRITICAL WARNING: Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who discontinue tenofovir therapy. 1
- Hepatic function must be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation. 1
- Do not let tenofovir run out; refill prescriptions before supply is depleted. 1
Drug Interactions
- Tenofovir should not be used in combination with other tenofovir-containing products (ATRIPLA®, COMPLERA®, DESCOVY®, GENVOYA®, ODEFSEY®, STRIBILD®, TRUVADA®, VEMLIDY®) or with adefovir (HEPSERA®). 1
- Neither TAF nor cobicistat-boosted elvitegravir is recommended with rifamycin drugs for tuberculosis treatment. 3
Lipid Effects
- TDF decreases plasma lipid levels more than TAF because TDF results in higher plasma tenofovir levels. 3
- The clinical significance of this lipid-lowering effect is unknown. 3
- TAF is associated with greater weight gain than TDF. 3
Pre-Treatment and Ongoing Monitoring Requirements
Before Initiating Therapy
- Obtain HIV testing with combination antigen-antibody assay (if acute HIV suspected, add HIV RNA testing). 6
- Measure serum creatinine and estimated creatinine clearance. 6
- Test for hepatitis B surface antigen (HBsAg) and hepatitis C antibody. 6
- Perform HLA-B*5701 testing if considering abacavir-containing regimens. 3
During Treatment
- HIV RNA testing within the first 6 weeks of starting therapy, then every 3 months until <50 copies/mL for 1 year, then every 6 months. 3
- For PrEP patients: HIV testing every 3 months and three-site STI screening (rectal, pharyngeal, urogenital) every 3 months. 6
- Renal function monitoring every 6-12 months, with more frequent monitoring (every 3-6 months) for high-risk patients. 6
Special Populations
Pregnancy
- There is a pregnancy registry for women taking antiretroviral medicines during pregnancy. 1
- Cobicistat should not be given in pregnancy due to inadequate plasma levels. 3
Breastfeeding
- Do not breastfeed while taking tenofovir, as it passes into breast milk and poses risk of HIV transmission to the baby. 1