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Tenofovir disoproxil
alt=Above: molecular structure of tenofovir disoproxil Below: 3D representation of a tenofovir disoproxil molecule
Clinical data
Pronunciation/ˌtəˈnoʊfəvɪər ˌdɪsəˈprɑːksəl/
Trade namesViread, others
Other namesBis(POC)PMPA
AHFS/Drugs.comMonograph
MedlinePlusa602018
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability25%
MetabolismEster hydrolysis
MetabolitesTenofovir
Identifiers
  • Bis{[(isopropoxycarbonyl)oxy]methyl} ({[(2R)-1-(6-amino-9H-purin-9-yl)-2-propanyl]oxy}methyl)phosphonate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.129.993 Edit this at Wikidata
Chemical and physical data
FormulaC19H30N5O10P
Molar mass519.448 g·mol−1
3D model (JSmol)
  • C[C@H](Cn1cnc2c1ncnc2N)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C
  • InChI=1S/C19H30N5O10P/c1-12(2)33-18(25)28-9-31-35(27,32-10-29-19(26)34-13(3)4)11-30-14(5)6-24-8-23-15-16(20)21-7-22-17(15)24/h7-8,12-14H,6,9-11H2,1-5H3,(H2,20,21,22)/t14-/m1/s1
  • Key:JFVZFKDSXNQEJW-CQSZACIVSA-N
Tenofovir
Clinical data
Other names9-(2-Phosphonyl-methoxypropyly)adenine (PMPA)
MedlinePlusa602018
ATC code
  • None
Pharmacokinetic data
Protein binding< 1%
MetabolismPhosphorylation
MetabolitesTenofovir diphosphate (active metabolite)
Elimination half-life17 hours
ExcretionKidney
Identifiers
  • ({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.129.993 Edit this at Wikidata
Chemical and physical data
FormulaC9H14N5O4P
Molar mass287.216 g·mol−1
3D model (JSmol)
  • O=P(O)(O)CO[C@H](C)Cn1c2ncnc(c2nc1)N
  • InChI=1S/C9H14N5O4P/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17)/t6-/m1/s1 checkY
  • Key:SGOIRFVFHAKUTI-ZCFIWIBFSA-N checkY
  (verify)

Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS.[3] It is generally recommended for use with other antiretrovirals.[3] It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure.[3] It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir,[3] and elvitegravir/cobicistat/emtricitabine/tenofovir.[4] It does not cure HIV/AIDS or hepatitis B.[3][5] It is available by mouth as a tablet or powder.[3]

Common side effects include nausea, rash, diarrhea, headache, pain, depression, and weakness.[3] Severe side effects include high blood lactate and an enlarged liver.[3] There are no absolute contraindications.[3] It is often recommended during pregnancy and appears to be safe.[3] It is a nucleotide reverse transcriptase inhibitor and works by decreasing the ability of the viruses to replicate.[3]

Tenofovir was patented in 1996 and approved for use in the United States in 2001.[6] It is on the World Health Organization's List of Essential Medicines.[7] It is available in the United States as a generic medication as of 2017.[8]

Medical uses

[edit]

Tenofovir disoproxil is used for HIV-1 infection and chronic hepatitis B treatment. For HIV-1 infection, tenofovir is indicated in combination with other antiretroviral agents for people 2 years of age and older. For chronic hepatitis B patients, tenofovir is indicated for patients 12 years of age and older.[9]

HIV risk reduction

[edit]

Tenofovir can be used for HIV prevention in people who are at high risk for infection through sexual transmission or injecting drug use. A Cochrane review examined the use of tenofovir for prevention of HIV before exposure and found that both tenofovir alone and the tenofovir/emtricitabine combination decreased the risk of contracting HIV for high risk patients.[10] The U.S. Centers for Disease Control and Prevention (CDC) also conducted a study in partnership with the Thailand Ministry of Public Health to ascertain the effectiveness of providing people who inject drugs illicitly with daily doses of tenofovir as a prevention measure. The results revealed a 48.9% reduced incidence of the virus among the group of subjects who received the drug in comparison to the control group who received a placebo.[11]

Adverse effects

[edit]

Tenofovir disoproxil is generally well tolerated with low discontinuation rates among the HIV and chronic hepatitis B population.[12] There are no contraindications for use of this drug.[9] The most commonly reported side effects due to use of tenofovir disoproxil were dizziness, nausea, and diarrhea.[12] Other adverse effects include depression, sleep disturbances, headache, itching, rash, and fever. The US boxed warning cautions potential onset of lactic acidosis or liver damage due to use of tenofovir disoproxil.[13]

Long term use of tenofovir disoproxil is associated with nephrotoxicity and bone loss. Presentation of nephrotoxicity can appear as Fanconi syndrome, acute kidney injury, or decline of glomerular filtration rate (GFR).[14] Discontinuation of tenofovir disoproxil can potentially lead to reversal of renal impairment. Nephrotoxicity may be due to proximal tubules accumulation of Tenofovir disoproxil leading to elevated serum concentrations.[12]

Interactions

[edit]

Tenofovir interacts with didanosine and HIV-1 protease inhibitors. Tenofovir increases didanosine concentrations and can result in adverse effects such as pancreatitis and neuropathy. Tenofovir also interacts with HIV-1 protease inhibitors such as atazanavir, by decreasing atazanavir concentrations while increasing tenofovir concentrations.[9] In addition, since tenofovir is excreted by the kidney, medications that impair renal function can also cause problems.[15]

Pharmacology

[edit]

Mechanism of action

[edit]

Tenofovir disoproxil is a nucleotide analog reverse-transcriptase inhibitor (NtRTI).[16] It selectively inhibits viral reverse transcriptase, a crucial enzyme in retroviruses such as human immunodeficiency virus (HIV), while showing limited inhibition of human enzymes, such as DNA polymerases α, β, and mitochondrial DNA polymerase γ.[9][16] In vivo tenofovir disoproxil fumarate is converted to tenofovir, an acyclic analog of deoxyadenosine 5'-monophosphate (dAMP). Tenofovir lacks a hydroxyl group in the position corresponding to the 3' carbon of the dAMP, preventing the formation of the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation.[16] Once incorporated into a growing DNA strand, tenofovir causes premature termination of DNA transcription, preventing viral replication.[16]

Pharmacokinetics

[edit]

Tenofovir disoproxil is a prodrug that is quickly absorbed from the gut and cleaved to release tenofovir.[9] Inside cells, tenofovir is phosphorylated to tenofovir diphosphate (which is analogous to a triphosphate, as tenofovir itself already has one phosphonate residue), the active compound that inhibits reverse transcriptase via chain termination.[15][16]

In fasting persons, bioavailability is 25%, and highest blood plasma concentrations are reached after one hour.[16] When taken with fatty food, highest plasma concentrations are reached after two hours, and the area under the curve is increased by 40%.[16] It is an inhibitor of cytochrome P450 1A2.[17]

Tenofovir is mainly excreted via the kidneys, both by glomerular filtration and by tubular secretion using the transport proteins OAT1, OAT3 and ABCC4.[15]

Detection in body fluids

[edit]

Tenofovir may be measured in plasma by liquid chromatography. Such testing is useful for monitoring therapy and to prevent drug accumulation and toxicity in people with kidney or liver problems.[18][19][20]

Chemistry

[edit]

Tenofovir is a derivative of adenine and this was the chemical starting point for its first published synthesis[21] which was included in patents to the compound.[22] During drug development, attention switched to the phosphonate ester derivative, tenofovir disoproxil, which was the subject of extensive process chemistry to provide a viable manufacturing route.

Adenine is first reacted with a chiral version of propylene carbonate with R absolute configuration, using sodium hydroxide as base. Under these conditions, the reaction is regioselective, with alkylation occurring exclusively in the imidazole ring and at the less-hindered carbon of the dioxolane. In the second step, the hydroxyl group is reacted with a phosphonic acid derivative, using tert-butyllithium as base to ensure selective O-alkylation, with the formation of an ether bond. Tenofovir is formed when the diethyl phosphonate group is converted to its acid using trimethylsilyl chloride in the presence of sodium bromide, a further refinement of the original manufacturing route.[23][24][25] The synthesis of the alternative ester in tenofovir disoproxil is completed by alkylation with the appropriate chloromethyl ether derivative and this may be purified as its fumarate salt.[23]

History

[edit]

Tenofovir was initially synthesized by Antonín Holý at the Institute of Organic Chemistry and Biochemistry of the Czechoslovak Academy of Sciences in Prague. The patent filed in 1986 makes no mention of the potential use of the compound for the treatment of HIV infection but claims activity against herpes simplex virus.[22]

In 1985, Erik De Clercq and Holý described the activity of PMPA against HIV in cell culture.[26] Shortly thereafter, a collaboration with the biotechnology company Gilead Sciences led to the investigation of PMPA's potential as a treatment for HIV infected patients. In 1997 researchers from Gilead and the University of California, San Francisco demonstrated that tenofovir exhibits anti-HIV effects in humans when dosed by subcutaneous injection.[27]

The initial form of tenofovir used in these studies had limited potential for widespread use because it poorly penetrated cells and was not absorbed when given by mouth. Gilead developed a pro-drug version of tenofovir, tenofovir disoproxil. This version of tenofovir is often referred to simply as "tenofovir". In this version of the drug, the two negative charges of the tenofovir phosphonic acid group are masked, thus enhancing oral absorption.

Tenofovir disoproxil was approved in the U.S. in 2001, for the treatment of HIV, and in 2008, for the treatment of chronic hepatitis B.[28][29]

Drug forms

[edit]

Tenofovir disoproxil can be taken by mouth and is sold under the brand name Viread, among others.[30] Tenofovir disoproxil is a pro-drug form of tenofovir phosphonate, which is liberated intracellularly and converted to tenofovir disphophate.[31] It is marketed by Gilead Sciences (as the fumarate, abbreviated TDF).[32]

Tenofovir disoproxil is also available in pills which combine a number of antiviral drugs into a single dose. Well-known combinations include Atripla (tenofovir disoproxil/emtricitabine/efavirenz), Complera (tenofovir disoproxil/emtricitabine/rilpivirine), Stribild (tenofovir disoproxil/emtricitabine/elvitegravir/cobicistat), and Truvada (tenofovir disoproxil/emtricitabine).[30]

Gilead has created a second pro-drug form of the active drug, tenofovir diphosphate, called tenofovir alafenamide. It differs from tenofovir disoproxil due to its activation in the lymphoid cells. This allows the active metabolites to accumulate in those cells, leading to lower systemic exposure and potential toxicities.[12]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Tenofovir disoproxil

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from Grokipedia
Tenofovir disoproxil fumarate (TDF), marketed under the brand name Viread, is a analogue used as an antiretroviral to treat HIV-1 infection and chronic (HBV) infection. As a of tenofovir, it is orally administered and converted intracellularly to its active diphosphate form, which competitively inhibits HIV-1 and HBV , thereby suppressing . TDF is typically used in combination with other antiretroviral agents for HIV management and as monotherapy or in combination for HBV, with a standard adult dosage of 300 mg once daily. First approved by the U.S. (FDA) on October 26, 2001, for the treatment of HIV-1 in adults in , TDF represented a significant advancement in antiretroviral options due to its once-daily dosing and potent activity against both and HBV. In 2008, the FDA expanded its approval to include chronic HBV treatment in adults, with further extensions to pediatric patients aged 12 years and older in 2012 and down to 2 years in later updates. It is also indicated for (PrEP) in combination formulations like emtricitabine/TDF (Truvada), approved in 2012. Available as 300 mg film-coated tablets, TDF is generally well-tolerated but requires monitoring for renal function and density due to potential long-term effects such as proximal renal tubulopathy and decreased . While effective in achieving viral suppression and improving clinical outcomes in both and HBV patients, TDF's use has been somewhat supplanted in recent years by (TAF), a modified with a lower risk of renal and bone toxicity, though TDF remains a cornerstone therapy, particularly in resource-limited settings and for PEP (). Its inclusion on the World Health Organization's List of Essential Medicines underscores its global importance in managing these viral infections.

Medical uses

Treatment of HIV infection

Tenofovir disoproxil fumarate (TDF) is approved by the U.S. Food and Drug Administration for the treatment of HIV-1 infection in adults and pediatric patients as part of highly active antiretroviral therapy (HAART) regimens, in combination with other antiretroviral agents from different classes. It belongs to the nucleotide reverse transcriptase inhibitor (NRTI) class and is commonly used as a backbone in fixed-dose combinations, such as with emtricitabine (as Truvada) or lamivudine, alongside integrase strand transfer inhibitors like dolutegravir or protease inhibitors. This combination approach enhances viral suppression while minimizing the risk of resistance development. The recommended adult dose is 300 mg once daily, taken orally without regard to food, with adjustments required for patients with impaired renal function ( clearance <50 mL/min). In pediatric patients aged 2 years and older weighing at least 17 kg, dosing is 8 mg/kg of tenofovir disoproxil fumarate once daily (maximum 300 mg), which approximates 208 mg/m² based on body surface area. Renal function monitoring is essential during treatment, particularly in patients with risk factors. Pivotal clinical trials demonstrated high efficacy of TDF-containing regimens in treatment-naïve patients. In Study 903, a randomized trial comparing TDF plus lamivudine and efavirenz versus stavudine plus lamivudine and efavirenz, 80% of patients in the TDF arm achieved HIV-1 RNA levels below 400 copies/mL at 48 weeks, with 76% below 50 copies/mL. Similarly, Study 934 showed that emtricitabine plus TDF and efavirenz resulted in 84% of patients reaching HIV-1 RNA below 400 copies/mL and 80% below 50 copies/mL at 48 weeks, supporting the approval of Truvada. TDF's once-daily dosing and high genetic barrier to resistance have facilitated its long-term use in resource-limited settings, where it forms the NRTI backbone of first-line regimens recommended by the World Health Organization, contributing to sustained viral suppression in over 80% of adherent patients in global programs.

Pre-exposure prophylaxis for HIV

Tenofovir disoproxil fumarate, combined with emtricitabine (marketed as Truvada), received U.S. Food and Drug Administration (FDA) approval in 2012 for daily oral use as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in uninfected adults at high risk. This indication was expanded in 2018 to include HIV-negative adolescents weighing at least 35 kg who are at risk through sexual activity or injection drug use. In 2015, the World Health Organization (WHO) issued a strong recommendation for offering oral PrEP containing tenofovir disoproxil fumarate as an additional prevention choice for people at substantial risk of HIV acquisition, prioritizing key populations such as men who have sex with men, transgender women, sex workers, people who inject drugs, and serodiscordant couples. Clinical trials have established the efficacy of tenofovir disoproxil-emtricitabine PrEP in preventing HIV acquisition among high-risk uninfected individuals. The iPrEx trial, involving men who have sex with men and transgender women, demonstrated a 44% overall reduction in HIV incidence with daily dosing, rising to 92% efficacy among participants with plasma drug levels indicating more than 90% adherence. These findings were corroborated by the Partners PrEP study in heterosexual serodiscordant couples, which reported a 75% reduction in HIV-1 acquisition, and the TDF2 trial among young heterosexual adults in Botswana, showing a 62% reduction. High adherence remains critical for achieving maximal protection, as suboptimal use correlates with diminished efficacy across these studies. The standard dosing for tenofovir disoproxil-emtricitabine PrEP is one oral tablet daily, containing 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine, alongside regular HIV testing every three months to detect any seroconversion early. For men who have sex with men, evidence from the IPERGAY trial supports an on-demand "2-1-1" regimen—two tablets taken 2 to 24 hours before sex, followed by one tablet 24 hours later and another 48 hours after the first dose—resulting in an 86% reduction in HIV acquisition. Successful PrEP implementation emphasizes adherence counseling, behavioral support, and linkage to comprehensive HIV prevention services, including condom provision and sexually transmitted infection screening. As of 2024, approximately 8 million people globally had initiated PrEP, predominantly tenofovir-based formulations, though scale-up continues to address gaps in access for high-risk populations and meet the 2025 target of 21.2 million users.

Treatment of chronic hepatitis B

Tenofovir disoproxil fumarate (TDF) received FDA approval in 2008 for the treatment of chronic hepatitis B (CHB) in adults with compensated liver disease and evidence of viral replication, including those with HIV/HBV co-infection, with expansion in 2016 to pediatric patients aged 2 years and older weighing at least 10 kg. The standard dosing regimen is 300 mg orally once daily for adults, administered with or without food; for pediatrics, it is weight-based (e.g., 8 mg/kg once daily for 10–<25 kg, up to 300 mg maximum), alongside routine monitoring of serum HBV DNA levels every 3 to 6 months and liver function tests to evaluate virological response, alanine aminotransferase normalization, and potential flares. Renal function and bone density monitoring are recommended, particularly in children. Clinical efficacy was established in two phase III randomized controlled trials comparing TDF to adefovir dipivoxil. At 48 weeks, 68% of HBeAg-negative patients and 76% of HBeAg-positive patients on TDF achieved undetectable HBV DNA levels (<400 copies/mL), significantly outperforming adefovir. Histological improvement, defined as at least a 2-point reduction in the Knodell necroinflammation score without worsening fibrosis, occurred in 72% to 74% of TDF-treated patients across both cohorts. HBeAg seroconversion rates reached approximately 21% in HBeAg-positive patients at this time point. Long-term extension studies of these trials have shown sustained viral suppression with TDF monotherapy, with over 90% of patients maintaining undetectable HBV DNA after up to 8 years of treatment. Resistance development remains rare, at less than 1%, attributable to TDF's high genetic barrier that minimizes selection of resistant HBV variants. Abrupt discontinuation of TDF in CHB patients poses substantial risks, including virological relapse in up to 80% and severe alanine aminotransferase flares in 20% to 30%, which can progress to hepatic decompensation in those with advanced fibrosis. Guidelines therefore recommend indefinite therapy for most patients, with careful post-discontinuation monitoring of HBV DNA and liver enzymes every 1 to 3 months, and immediate reinitiation of antiviral therapy upon relapse. The 2025 AASLD guidelines endorse TDF as a first-line nucleos(t)ide analogue for CHB due to its potent efficacy and low resistance profile. In HIV/HBV co-infected individuals, TDF is integrated into combination antiretroviral regimens to address both infections simultaneously.

Safety profile

Adverse effects

Tenofovir disoproxil fumarate (TDF) is associated with several common adverse effects, primarily gastrointestinal and systemic symptoms occurring in more than 10% of users, including nausea, diarrhea, headache, and asthenia (fatigue or weakness); these are typically mild and resolve spontaneously without intervention. Renal toxicity represents a significant concern with TDF, manifesting as proximal tubulopathy, including characterized by hypophosphatemia, glycosuria, and proteinuria, with reduced glomerular filtration rate (GFR) observed in 2-5% of long-term users. Risk factors for this toxicity include advanced age over 50 years and low body weight, which may increase drug exposure and tubular accumulation. Bone effects from TDF include a mean annual loss of bone mineral density (BMD) of 1-2% at the hip and spine, particularly during the first year of therapy, with an associated increase in fracture risk of 2-6% over comparators; these risks appear elevated in pre-exposure prophylaxis (PrEP) users based on meta-analyses evaluating long-term exposure. Lactic acidosis and hepatic steatosis are rare but severe adverse effects linked to the nucleoside reverse transcriptase inhibitor (NRTI) class, including TDF, with potential for fatal outcomes due to mitochondrial dysfunction; symptoms include abdominal pain, nausea, and rapid breathing, necessitating immediate discontinuation. Management of TDF-related adverse effects involves dose adjustment (e.g., every 48 hours) or discontinuation when creatinine clearance falls below 50 mL/min, alongside avoidance of concurrent nephrotoxic agents that may exacerbate renal issues.

Drug interactions

Tenofovir disoproxil fumarate (TDF) exhibits clinically significant drug interactions primarily through additive nephrotoxicity and alterations in renal transporter activity, such as inhibition of organic anion transporters (OAT1 and OAT3), which can elevate plasma concentrations of TDF or coadministered agents. These interactions necessitate careful monitoring of renal function, including creatinine clearance (CrCl), particularly in patients with preexisting renal impairment. Coadministration with nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) at high doses, aminoglycosides (e.g., gentamicin), and cyclosporine, increases the risk of renal impairment due to additive effects on kidney function. Concurrent use should be avoided when possible, or CrCl should be closely monitored to detect early signs of toxicity, as these agents may exacerbate TDF-related proximal tubulopathy. This heightened renal risk is distinct from TDF's intrinsic adverse effects but can compound them, leading to recommendations for dose adjustments or discontinuation if CrCl declines below 50 mL/min. Among antiretrovirals, boosted protease inhibitors (PIs) like atazanavir/ritonavir increase TDF exposure by 20-40% through ritonavir-mediated inhibition of renal OAT1 and OAT3 transporters, potentially elevating the risk of TDF-associated toxicities. For example, coadministration with atazanavir/ritonavir results in a 25% increase in TDF area under the curve (AUC), while lopinavir/ritonavir yields a 32% rise. No dose adjustment for TDF is required, but enhanced monitoring for renal function and tenofovir-related adverse events is advised; dose separation is not routinely recommended for these combinations but may be considered in high-risk cases. TDF significantly interacts with didanosine, increasing didanosine AUC by 40-60% regardless of fasting or fed state, which heightens the risk of didanosine-related toxicities including pancreatitis and peripheral neuropathy. To mitigate this, the didanosine dose should be reduced to 250 mg for patients over 60 kg or 200 mg for those under 60 kg when coadministered with TDF, with close clinical monitoring for adverse effects. Staggered administration (e.g., didanosine on an empty stomach two hours before or after TDF) can further minimize the interaction. For hepatitis B virus (HBV) therapies, TDF shows no major pharmacokinetic interactions with entecavir, allowing safe coadministration without dose adjustments. However, combination with adefovir dipivoxil carries an additive risk of renal toxicity due to shared nephrotoxic potential, and such use should be avoided or monitored intensively for declines in renal function. With appropriate adjusted dosing and monitoring, these interactions rarely lead to treatment discontinuation, occurring in less than 1% of cases attributable to interaction-related adverse events in clinical studies.

Contraindications and monitoring

Tenofovir disoproxil is contraindicated in patients with known hypersensitivity to tenofovir disoproxil fumarate or any of its components. It is also contraindicated in individuals with severe renal impairment (creatinine clearance [CrCl] <10 mL/min) not receiving hemodialysis, as safety and efficacy have not been established in this population. Relative contraindications include pre-existing renal disease, where dosing adjustments based on CrCl are required (e.g., 300 mg every 48 hours for CrCl 30–49 mL/min and every 72 hours for CrCl 10–29 mL/min), and osteoporosis or history of pathologic fractures, due to risks of bone mineral density loss. Use during pregnancy is not associated with increased risk of adverse pregnancy-related outcomes based on published studies in HBV-infected subjects; a pregnancy exposure registry monitors outcomes in women exposed to tenofovir disoproxil fumarate during pregnancy. Monitoring protocols emphasize renal function assessment, including baseline serum creatinine, estimated glomerular filtration rate (eGFR), urine glucose, and urine protein, followed by evaluations every 3–6 months or more frequently in at-risk patients (e.g., those with comorbidities or concurrent nephrotoxins). For long-term users, particularly those on pre-exposure prophylaxis (PrEP), annual bone mineral density screening is advised if risk factors for osteoporosis are present. In PrEP contexts, guidelines recommend HIV testing and sexually transmitted infection (STI) screening every 3 months, with renal function assessed at baseline, at 3 months, and every 6 months thereafter (more frequently if risk factors are present) to detect early changes and ensure ongoing safety. For chronic hepatitis B treatment, close monitoring for HBV reactivation is essential upon discontinuation, as severe acute exacerbations with alanine aminotransferase (ALT) flares occur in approximately 20–30% of cases, potentially leading to hepatic decompensation. In special populations, elderly patients require dose adjustments based on age-related declines in renal function, with cautious initiation and more frequent monitoring. Pediatric use is approved for HIV and HBV in children aged 2 years and older weighing at least 10 kg, but data remain limited outside HIV treatment contexts, necessitating individualized assessment.

Pharmacology

Mechanism of action

Tenofovir disoproxil is a prodrug that undergoes hydrolysis in plasma by esterases to yield tenofovir, which is then transported into cells and sequentially phosphorylated by cellular enzymes—adenylate kinase to tenofovir monophosphate, and nucleoside diphosphate kinase to the active metabolite tenofovir diphosphate (TFV-DP). This activation process occurs efficiently in both lymphoid and hepatic cells, enabling TFV-DP to exert antiviral effects. TFV-DP competitively inhibits HIV-1 reverse transcriptase (RT) and hepatitis B virus (HBV) polymerase by binding to the enzyme's nucleotide-binding site, mimicking the natural substrate deoxyadenosine triphosphate (dATP). Upon incorporation into the growing viral DNA chain by these enzymes, TFV-DP causes chain termination because it lacks a 3'-hydroxyl group required for further nucleotide addition. This mechanism disrupts viral DNA synthesis essential for replication. The dual activity of tenofovir against HIV-1 and HBV stems from the structural and functional similarities between HIV-1 RT and HBV polymerase, both of which are reverse transcriptases that rely on analogous polymerization steps. Tenofovir exhibits a high genetic barrier to resistance, as significant phenotypic resistance in HIV-1 typically requires multiple mutations in RT, such as K65R (which reduces binding affinity) often combined with K70E or thymidine analog mutations (TAMs). At therapeutic concentrations, TFV-DP shows no significant inhibition of host DNA polymerases (α, β, δ) or mitochondrial polymerase γ, ensuring selectivity for viral enzymes.

Pharmacokinetics

Tenofovir disoproxil fumarate (TDF) is a prodrug with an oral bioavailability of approximately 25% as tenofovir following rapid hydrolysis by plasma and tissue esterases after oral administration. Maximum plasma concentrations of tenofovir are achieved within 1 hour in fasted conditions, and administration with food increases the area under the curve (AUC) by about 40% and peak concentration (Cmax) by 14%, though this does not alter dosing recommendations. Following absorption, tenofovir exhibits a of approximately 1.2 L/kg and low of less than 0.7%. It penetrates the (CSF) to a limited extent, with CSF:plasma ratios ranging from 0.01 to 0.07, reflecting modest exposure. TDF undergoes no hepatic (CYP) metabolism; instead, it is converted to tenofovir by esterases, and tenofovir is then phosphorylated intracellularly first to tenofovir monophosphate by adenylate kinase 2 and subsequently to the active diphosphate form. Elimination of tenofovir occurs primarily via the kidneys, with 70-80% of the dose recovered unchanged in urine through a combination of glomerular filtration and active tubular secretion mediated by organic anion transporters OAT1 and OAT3. The elimination is approximately 17 hours, leading to steady-state concentrations achieved within 5-7 days of daily dosing. In special populations, tenofovir clearance is reduced in renal impairment, necessitating dose adjustments when clearance falls below 50 mL/min. Recent studies in obese individuals indicate lower tenofovir plasma concentrations compared to non-obese counterparts, yet no dose adjustment is required, unlike for certain other antiretrovirals.

Detection in biological fluids

Detection of tenofovir disoproxil and its , tenofovir (TFV), in biological fluids is essential for assessing therapeutic adherence, particularly in HIV (PrEP) and treatment regimens, as well as for monitoring potential toxicity. High-performance liquid chromatography-tandem (HPLC-MS/MS) is a widely used analytical method for quantifying TFV in plasma, offering high sensitivity with a lower limit of quantification (LLOQ) of 10 ng/mL and linearity up to 10,000 ng/mL. This technique involves protein precipitation of plasma samples followed by , enabling precise measurement in small volumes (e.g., 50 μL). For , similar LC-MS/MS methods achieve detection limits as low as 0.5 μg/mL, supporting adherence evaluation through renal excretion analysis. Indirect detection via dipstick testing for phosphaturia, a marker of tenofovir-induced renal tubular dysfunction, provides a non-invasive screen for chronic exposure, though it lacks specificity for the drug itself. In plasma, TFV concentrations correlate strongly with recent dosing adherence in PrEP and therapy. Therapeutic post-dose levels typically range from 40 to 400 ng/mL, with trough concentrations above 40 ng/mL indicating consistent daily dosing and protection against acquisition. For instance, plasma TFV levels of at least 35.5 ng/mL correspond to adherence with seven doses per week, while concentrations below 10 ng/mL signal non-adherence requiring intervention. Complementary intracellular measurement of tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) via LC-MS/MS provides a longer-term adherence metric, where levels exceeding 700 fmol per 3 mm punch reflect recent dosing (e.g., four or more doses weekly) and correlate with virologic suppression. Urine serves as a practical matrix for TFV detection due to its primary renal route, with the remaining detectable for up to 48 hours post-dose using point-of-care lateral flow immunoassays. These assays, which employ antibody-based detection with a cutoff around 1,500 ng/mL, offer rapid (under 5 minutes) qualitative results for short-term adherence, outperforming self-reports in PrEP settings. Such tests are particularly valuable for real-time counseling, as undetectable TFV after 48 hours indicates missed doses and prompts adherence support. Hair analysis quantifies cumulative TFV exposure over months, providing an objective adherence integrated into growing shafts. TFV levels in , measured by LC-MS/MS with an LLOQ of 0.002 ng/mg, typically range from 0.01 to 0.1 ng/mg in adherent individuals, with concentrations above 0.021 ng/mg distinguishing daily (seven doses/week) from intermittent dosing. This method correlates linearly with dosing frequency (76% increase per twofold dose rise) and is useful for retrospective assessment in clinical trials. Lateral flow assays for urine TFV detection, validated with 96% sensitivity and 100% specificity compared to LC-MS/MS, and anticipated to under $2 per test at scale, have been advanced in 2024–2025 studies to enhance accessibility in low-resource settings by reducing reliance on laboratory infrastructure, enabling immediate adherence feedback and improving PrEP continuation rates. They address gaps in traditional methods by offering scalability for global prevention programs. In forensic contexts, TFV remains stable in postmortem plasma and for up to 72 hours at ambient temperatures, allowing reliable detection via LC-MS/MS despite potential postmortem redistribution. This stability supports toxicological analysis in cases involving overdose or compliance issues, with validated methods confirming drug presence without significant degradation in early postmortem intervals.

Chemistry

Chemical structure and properties

Tenofovir disoproxil has the molecular formula C19_{19}H30_{30}N5_5O10_{10}P and a molecular weight of 519.45 g/mol. It is most commonly formulated as the fumarate salt, with the molecular formula C23_{23}H34_{34}N5_5O14_{14}P and a molecular weight of 635.52 g/mol. The chemical structure of tenofovir disoproxil consists of an adenine nucleoside analog featuring an acyclic propyl chain in place of the ribose sugar, with a phosphonate group at the 5'-position esterified as diisopropyl esters (disoproxil moiety). This prodrug design enhances oral bioavailability by masking the polar phosphonate, which is subsequently hydrolyzed in vivo to the active tenofovir. The molecule contains a single chiral center at the carbon bearing the phosphonate-linked methylene and methyl groups, with the pharmaceutical form utilizing the (R)-enantiomer; it is optically active but prepared enantiomerically pure, avoiding stereoisomer mixtures. Crystal structure analyses, including a 2017 study on its stability-enhanced solid form, emphasize the conformation of the ester bonds and hydrogen bonding networks that influence solid-state properties. Physicochemical properties include high aqueous for the fumarate salt, approximately 13.4 mg/mL at 25°C, classifying it as freely soluble. The pKa value is 3.75, primarily associated with the protonated or residual acidic functionality, while the esterified does not exhibit the dual pKa (around 3.8 and 7.1) seen in the parent tenofovir due to masking. In terms of stability, tenofovir disoproxil undergoes rapid in aqueous environments, cleaving the isopropyl bonds to yield tenofovir, with a of about 16.6 hours at intestinal (6.8); however, it remains stable in solid form at under dry conditions, with low hygroscopicity in its free base variant.

Synthesis and formulation

The synthesis of tenofovir disoproxil fumarate involves a multi-step process starting from and phosphonic acid precursors. Adenine is first alkylated with (R)-4-methyl-1,3-dioxolan-2-one to form (R)-9-(2-hydroxypropyl), which is then coupled with diisopropyl p-toluenesulfonyloxymethyl in the presence of a base like magnesium tert-butoxide to yield the diisopropyl ester of tenofovir. Subsequent of the phosphonate esters using trimethylsilyl bromide produces tenofovir, the free phosphonic acid. Finally, alkylative esterification of tenofovir with chloromethyl isopropyl , followed by formation of the fumarate salt, affords tenofovir disoproxil fumarate. Tenofovir disoproxil is designed as a of tenofovir to enhance and oral . The parent tenofovir, being a dianion at physiological , exhibits poor permeability and low oral absorption (<5%); the disoproxil moiety, consisting of two isopropyloxycarbonyloxymethyl groups on the , increases , enabling better cellular uptake and subsequent intracellular conversion to the active form, with oral improved to approximately 25%. Manufacturing of tenofovir disoproxil fumarate adheres to (GMP) standards, originally developed by . Process optimizations, such as telescoped procedures and improved conditions, have enhanced yields and reduced waste in the three-step route from the tenofovir ester. Patent expiration in 2017 in the and 2018-2019 in other major markets enabled generic production using similar synthetic pathways, with Indian manufacturers like and Matrix Laboratories scaling up active pharmaceutical (API) synthesis to meet global demand for affordable antiretrovirals. Formulation of tenofovir disoproxil into tablets addresses challenges like its bitter taste and . Film coating with polymers such as masks bitterness, improving patient compliance, while excipients including monohydrate, , and croscarmellose sodium ensure tablet integrity and disintegration. Stability is maintained through controlled and moisture levels during compression, preventing degradation of the ester linkages. Recent efforts in tenofovir disoproxil synthesis focus on , with a 2023 analysis identifying use as a major environmental hotspot and proposing innovations like improved recovery and alternative synthesis routes, potentially reducing organic consumption by up to 80% in optimized processes.

History

Development and discovery

Tenofovir, the active moiety of tenofovir disoproxil, originated from research on acyclic phosphonates conducted in the early at the Institute of Organic Chemistry and Biochemistry (IOCB) of the Czechoslovak Academy of Sciences in . Czech chemist Antonín Holý and his team synthesized tenofovir (9-(R)-(2-phosphonomethoxypropyl), or PMPA) as an analog of earlier compounds like HPMPA, initially exploring broad-spectrum antiviral potential without specific focus on , which had only recently been identified. Holý filed the original for tenofovir in 1984, but it did not reference treatment applications. In the early 1990s, licensed the IOCB's technology, enabling further development in the United States. Gilead researchers, building on Holý's foundational work, identified tenofovir's potent activity against -1 reverse , with an of approximately 0.04 μM for the active diphosphate form in enzymatic assays. Preclinical studies in cell cultures confirmed its efficacy against HIV replication, but the parent compound exhibited poor oral of less than 4% due to limited intestinal absorption and low membrane permeability. To address bioavailability challenges, developed tenofovir disoproxil as a , incorporating isopropyl carboxymethyl groups to enhance plasma stability, cellular uptake, and conversion to the active form intracellularly. This modification achieved oral of about 25% in animal models, demonstrating antiviral activity in woodchuck models and HIV-infected humanized mice after oral dosing. The approach was covered in U.S. 5,922,695, filed in 1997, which detailed methods for preparing tenofovir disoproxil and its derivatives for therapeutic use. Early preclinical testing revealed renal toxicity concerns, including malabsorption and tubular damage in at high doses, prompting dose optimization to balance and before advancing to clinical stages. Retrospectives in 2025 have increasingly highlighted Holý's pivotal role, expanding historical narratives beyond U.S.-centric accounts to credit the Czech origins of the class that revolutionized and treatments. These acknowledgments, including tributes in , underscore the collaborative path from Prague's laboratories to global .

Regulatory approvals and key milestones

Tenofovir disoproxil fumarate (TDF) received its initial approval from the U.S. (FDA) on October 26, 2001, under the brand name Viread, for use in combination with other antiretroviral agents to treat HIV-1 infection in treatment-experienced adults. The (EMA) granted marketing authorization for Viread on February 5, 2002, for the same indication in adults. In 2008, the FDA expanded Viread's approval to include the treatment of chronic hepatitis B in adults, based on pivotal phase 3 trials 102 and 103, which demonstrated TDF's superiority to adefovir dipivoxil in reducing HBV DNA levels and normalizing alanine aminotransferase. A significant milestone occurred in 2012 when the FDA approved Truvada (emtricitabine/TDF) on July 16 for pre-exposure prophylaxis (PrEP) to reduce the risk of HIV acquisition in adults at high risk, marking the first such approval for HIV prevention. This followed interim guidance from the Centers for Disease Control and Prevention (CDC) on August 10, 2012, recommending PrEP for certain high-risk populations. In 2009, the World Health Organization (WHO) prequalified the first generic versions of TDF, facilitating access in low- and middle-income countries. TDF was incorporated into fixed-dose combinations, with Atripla (efavirenz/emtricitabine/TDF) approved by the FDA on July 12, 2006, as the first complete single-tablet regimen for treatment. Complera (rilpivirine/emtricitabine/TDF) received FDA approval on August 10, 2011, offering an alternative for treatment-naïve adults. Patent challenges by generic manufacturers culminated in the entry of generic Truvada in the U.S. market in September 2020, following settlements that resolved exclusivity disputes. Post-marketing surveillance led to updates in product labeling, including a black box warning added upon initial FDA approval in 2001 for the risk of and severe with . In 2005, the label was revised to include recommendations for renal function monitoring due to observed declines in clearance associated with TDF use. As of 2025, the EMA conducted a review confirming the ongoing authorization of TDF-containing products like Truvada, despite the preference for (TAF) in many guidelines due to its improved renal and bone safety profile, while extending indications for pediatric use in specific formulations.

Society and culture

Available formulations

Tenofovir disoproxil fumarate (TDF) is primarily available as an oral monotherapy under the brand name Viread in film-coated tablet form at a standard adult dose of 300 mg, equivalent to 245 mg of tenofovir disoproxil. For pediatric use, lower-strength tablets are provided, including 150 mg TDF (equivalent to 123 mg tenofovir disoproxil), 200 mg TDF (equivalent to 163 mg tenofovir disoproxil), and 250 mg TDF (equivalent to 204 mg tenofovir disoproxil), suitable for patients based on body weight. Fixed-dose combination products incorporating TDF are commonly used for treatment to simplify regimens. Truvada combines 300 mg TDF with 200 mg emtricitabine in a single film-coated tablet. Atripla includes 300 mg TDF, 200 mg emtricitabine, and 600 mg in a film-coated tablet. Stribild contains 300 mg TDF, 200 mg emtricitabine, 150 mg elvitegravir, and 150 mg cobicistat in a single tablet formulation. These combinations are designed for once-daily oral administration in adults. For pediatric patients unable to swallow tablets, Viread is available as an oral powder for constitution into a suspension, providing 40 mg of tenofovir disoproxil fumarate (equivalent to 33 mg of tenofovir disoproxil) per gram of powder in multi-use bottles. No intravenous, topical, or other non-oral formulations of tenofovir disoproxil have been approved. All TDF formulations, including monotherapy and combinations, should be stored at controlled (20°C to 25°C or 68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F to 86°F), and protected from moisture by keeping containers tightly closed. Generic versions of tenofovir disoproxil and its fixed-dose combinations have become widely available following expirations, capturing the majority of the and driving down costs through among multiple manufacturers. While long-acting formulations of tenofovir prodrugs are in clinical trials as of , oral TDF remains the standard presentation. Some early TDF-based combinations have been phased out or superseded by versions using (TAF) due to improved renal and bone safety profiles. Tenofovir disoproxil, often used in combination formulations like Truvada for treatment and (PrEP), faced protections that varied by region, influencing global access to generics. In the United States, the key for the disoproxil fumarate combination (Truvada) expired in September 2020, enabling generic entry and competition. In the , the primary for tenofovir disoproxil (EP0915894B1) expired in July 2018, though some secondary patents extended protections in select countries until later dates. These expirations facilitated broader generic production, particularly in developing markets. Gilead Sciences, the original developer, granted voluntary licenses to multiple generic manufacturers, including 10 Indian companies, allowing production and distribution of tenofovir disoproxil fumarate for low- and middle-income countries since the mid-2000s, which supported affordable supply without compulsory licensing in . Although issued its first compulsory license for a different patented drug () in under the Patents Act, tenofovir disoproxil benefited from these voluntary agreements, enabling local manufacturing at reduced costs. Pricing disparities highlight access challenges: prior to generic availability in the US, a monthly supply of branded Truvada cost approximately $2,000 without insurance. In low-income countries, generic versions of tenofovir disoproxil-containing regimens, supported by programs like the US President's Emergency Plan for AIDS Relief (PEPFAR), are available for less than $1 per day, with first-line HIV treatments incorporating the drug priced below $45 per person per year through negotiated agreements with the Global Fund. These reductions stem from generic competition and bulk procurement, making the drug more accessible in resource-limited settings. Access initiatives have expanded availability, with the including tenofovir disoproxil on its Model List of since the 16th edition in 2009, prioritizing it for and management in systems. has committed to providing over 20 million courses of its therapeutics, including tenofovir-based options, to low- and middle-income countries annually as of 2023, though specific PrEP donations in focus on newer agents like rather than tenofovir alone. Legally, tenofovir disoproxil is classified as a drug in , requiring a prescription from a registered medical practitioner for dispensing. Discussions on over-the-counter access for PrEP formulations, including tenofovir disoproxil combinations, continue, with experts advocating for non-prescription availability to boost uptake among high-risk groups, though regulatory hurdles persist in most regions. Equity issues persist, with PrEP coverage using tenofovir-based regimens remaining below 10% in high-burden areas globally, according to the 2024 UNAIDS data book, due to socioeconomic barriers and limited distribution in key populations. In the US, generic competition for tenofovir disoproxil PrEP in 2025 has driven costs down by over 80% from branded prices, with monthly generics available for as low as $16-60, enhancing affordability but not fully addressing disparities in uptake.

References

  1. https://clinicalinfo.hiv-stage.od.nih.gov/en/drugs/tenofovir-disoproxil-fumarate/patient
  2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209550lbl.pdf
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC7163232/
  4. https://pubmed.ncbi.nlm.nih.gov/13130407/
  5. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-356_Viread.cfm
  6. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/fda-approved-hiv-medicines
  7. https://www.gilead.com/news/news-details/2008/us-food-and-drug-administration-approves-vireadr-for-chronic-hepatitis-b-in-adults
  8. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/tenofovir-df
  9. https://jamanetwork.com/journals/jama/fullarticle/199084
  10. https://www.nejm.org/doi/full/10.1056/NEJMoa051871
  11. https://pmc.ncbi.nlm.nih.gov/articles/PMC6519052/
  12. https://www.gilead.com/news/news-details/2012/us-food-and-drug-administration-approves-gileads-truvada-for-reducing-the-risk-of-acquiring-hiv
  13. https://www.nichd.nih.gov/newsroom/news/051618-PrEP
  14. https://www.who.int/publications/i/item/9789241509565
  15. https://www.nejm.org/doi/full/10.1056/NEJMoa1011205
  16. https://www.nejm.org/doi/full/10.1056/NEJMoa1108524
  17. https://www.nejm.org/doi/full/10.1056/NEJMoa1110711
  18. https://www.cdc.gov/hivnexus/hcp/prep/index.html
  19. https://www.nejm.org/doi/full/10.1056/NEJMoa1506273
  20. https://jhpiego.org/our-stories/p/prep-in-2025/
  21. https://www.cdc.gov/mmwr/volumes/73/wr/mm7347a3.htm
  22. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/021356s025ltr.pdf
  23. https://www.hepb.org/treatment-and-management/treatment/approved-drugs-for-children/
  24. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021356s027lbl.pdf
  25. https://www.nejm.org/doi/full/10.1056/NEJMoa0802878
  26. https://pubmed.ncbi.nlm.nih.gov/27658343/
  27. https://pmc.ncbi.nlm.nih.gov/articles/PMC8473499/
  28. https://www.aasld.org/aasld-announces-new-practice-guideline-treatment-chronic-hepatitis-b
  29. https://www.gilead.com/-/media/files/pdfs/medicines/liver-disease/viread/viread_pi.pdf
  30. https://pmc.ncbi.nlm.nih.gov/articles/PMC6111387/
  31. https://www.tandfonline.com/doi/full/10.2147/HIV.S308339
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC4844450/
  33. https://www.researchgate.net/publication/339395862_The_effect_of_tenofovir_disoproxil_fumarate_on_bone_mineral_density_a_systematic_review_and_meta-analysis
  34. https://www.hiv-druginteractions.org/interactions/2114/all
  35. https://go.drugbank.com/drugs/DB00300
  36. https://pmc.ncbi.nlm.nih.gov/articles/PMC9435983/
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC3153278/
  38. https://pubmed.ncbi.nlm.nih.gov/16291710/
  39. https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/0091270005281351
  40. https://www.hep-druginteractions.org/interactions/2802/all
  41. https://www.ovid.com/journals/hctri/pdf/10.1310/hct1506-231~discontinuation-of-tenofovir-disoproxil-fumarate-for
  42. https://www.sciencedirect.com/science/article/abs/pii/S1055329006602537
  43. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021356s058,022577s014lbl.pdf
  44. https://www.mdpi.com/2227-9059/11/3/752
  45. https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21356slr001_Viread_lbl.pdf
  46. https://journals.asm.org/doi/10.1128/aac.00138-06
  47. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106324
  48. https://hivdb.stanford.edu/dr-summary/resistance-notes/NRTI
  49. https://pubmed.ncbi.nlm.nih.gov/17442410/
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC3299895/
  51. https://pmc.ncbi.nlm.nih.gov/articles/PMC6563221/
  52. https://ascpt.onlinelibrary.wiley.com/doi/10.1002/psp4.12481
  53. https://pubmed.ncbi.nlm.nih.gov/35972856/
  54. https://pubmed.ncbi.nlm.nih.gov/29635209/
  55. https://www.sciencedirect.com/science/article/abs/pii/S0731708515002782
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC3800277/
  57. https://academic.oup.com/ofid/article/9/8/ofac405/6659247
  58. https://pmc.ncbi.nlm.nih.gov/articles/PMC5681370/
  59. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004732
  60. https://www.sciencedirect.com/science/article/pii/S2352301821001255/fulltext
  61. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083736
  62. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/dta.3033
  63. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(18)30024-5/fulltext
  64. https://hairlab.ucsf.edu/urine-biomarker-adherence
  65. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf337/8169862
  66. https://pubmed.ncbi.nlm.nih.gov/38900910/
  67. https://www.mdpi.com/1424-8247/18/6/899
  68. https://pubchem.ncbi.nlm.nih.gov/compound/Tenofovir-Disoproxil
  69. https://go.drugbank.com/salts/DBSALT000172
  70. https://www.mdpi.com/1420-3049/22/7/1182
  71. https://www.tga.gov.au/sites/default/files/auspar-tenofovir-disoproxil-fumarate-161110-pi.pdf
  72. https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021752s005lbl.pdf
  73. https://www.sciencedirect.com/science/article/pii/S0022354916418927
  74. https://pubs.acs.org/doi/10.1021/op1001337
  75. https://pmc.ncbi.nlm.nih.gov/articles/PMC2777719/
  76. https://pubs.acs.org/doi/10.1021/acsptsci.5c00237
  77. https://www.gilead.com/news/news-details/2006/gilead-announces-licensing-agreements-with-eight-india-based-companies-for-manufacturing-and-distribution-of-generic-versions-of-viread-in-the-developing-world
  78. https://www.pharmaexcipients.com/news/taste-masking-using-eudragit-l-100/
  79. https://www.wisdomlib.org/uploads/journals/wjpr/volume-10%2C-december-issue-14_18206.pdf
  80. https://www.uochb.cz/en/tenofovir
  81. https://www.uochb.cz/en/news/342/antonin-holy-85-story-of-tenofovir
  82. https://pmc.ncbi.nlm.nih.gov/articles/PMC8705530/
  83. https://www.sciencedirect.com/topics/neuroscience/tenofovir-disoproxil
  84. https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.12955
  85. https://www.vemlidyhcp.com/mechanism-of-action/
  86. https://patents.google.com/patent/US5922695A/en
  87. https://healthinstamps.com/antonin-holy-a-czech-scientist-who-created-tenofovir/
  88. https://pmc.ncbi.nlm.nih.gov/articles/PMC11860479/
  89. https://www.ema.europa.eu/en/medicines/human/EPAR/viread
  90. https://pubmed.ncbi.nlm.nih.gov/19792994/
  91. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a2.htm
  92. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021937TOC2.cfm
  93. https://www.gilead.com/news/news-details/2012/gileads-complera-non-inferior-to-atripla-among-treatment-nave-hiv-patients
  94. https://www.fiercepharma.com/special-report/top-10-drugs-losing-u-s-exclusivity-2020
  95. https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21356lbl.pdf
  96. https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021356s011lbl.pdf
  97. https://www.ema.europa.eu/en/documents/agenda/agenda-prac-meeting-1-4-september-2025_en.pdf
  98. https://efim.org/node/147163
  99. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021356s058%2C022577s014lbl.pdf
  100. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021752s064lbl.pdf
  101. https://www.accessdata.fda.gov/drugsatfda_docs/pepfar/203053PI.pdf
  102. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203100s030lbl.pdf
  103. https://www.drugpatentwatch.com/p/generic-api/TENOFOVIR%2BDISOPROXIL%2BFUMARATE
  104. https://pmc.ncbi.nlm.nih.gov/articles/PMC12315950/
  105. https://www.drugs.com/history/atripla.html
  106. https://www.healio.com/news/infectious-disease/20230817/qa-time-is-right-to-consider-overthecounter-hiv-prep-experts-say
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