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Emtricitabine/tenofovir

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This article is about the combination medication emtricitabine/tenofovir disoproxil. For the combination medication emtricitabine/tenofovir alafenamide, see Tenofovir alafenamide § combinations.

Emtricitabine/tenofovir, sold under the brand name Truvada among others, is a fixed-dose combination antiretroviral medication used to treat and prevent HIV/AIDS.[5][6] It contains the antiretroviral medications emtricitabine and tenofovir disoproxil.[7] For treatment, it must be used in combination with other antiretroviral medications.[7][8] For prevention before exposure, in those who are at high risk, it is recommended along with safer sex practices.[7] It does not cure HIV/AIDS.[5] Emtricitabine/tenofovir is taken by mouth.[7]

Emtricitabine/tenofovir
Combination of
EmtricitabineNucleoside reverse transcriptase inhibitor
Tenofovir disoproxilNucleotide analogue reverse transcriptase inhibitor
Clinical data
Trade namesTruvada, others
Other namesEmtricitabine/tenofovir disoproxil fumarate
AHFS/Drugs.comMonograph
MedlinePlusa612036
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
KEGG
NIAID ChemDB
  (verify)

Common side effects include headache, tiredness, trouble sleeping, abdominal pain, weight loss, and rash.[5] Serious side effects may include high blood lactate levels and enlargement of the liver.[7] Use of this medication during pregnancy does not appear to harm the fetus, but this has not been well studied.[1]

Emtricitabine/tenofovir was approved for medical use in the United States in 2004.[5] It is on the World Health Organization's List of Essential Medicines.[9] In the United States, emtricitabine/tenofovir was under patent by Gilead until 2020, but is now available as a generic worldwide.[10] In 2020, it was the 278th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[11][12]

Medical uses

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Emtricitabine/tenofovir is used both to treat and to prevent HIV/AIDS.[5] The U.S. National Institutes of Health (NIH) recommends antiretroviral therapy (ART) for all people with HIV/AIDS.[13]

HIV prevention

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The Centers for Disease Control and Prevention (CDC) recommends the use of emtricitabine/tenofovir for pre-exposure prophylaxis (PrEP) for uninfected, HIV-1 negative individuals that may be at risk for HIV-1 infection.[14][7] A Cochrane systematic review found a 51% relative risk reduction of contracting HIV with both tenofovir alone and the tenofovir/emtricitabine combination.[15] A JAMA systematic review found a similar relative risk reduction of 54% on average and greater reduction with greater adherence.[16] It was approved for PrEP against HIV infection in the United States in 2012.[17]

The CDC recommends PrEP be considered for the following high-risk groups:[18]

  • Individuals in an ongoing sexual relationship with an HIV-positive partner
  • Gay or bisexual men who either have had anal sex without a condom or been diagnosed with an STD in the past six months
  • Heterosexual men or women who do not regularly use condoms during sex with partners of unknown HIV status who are substantial risk
  • Injection of drugs in the last six months with sharing of equipment
  • Serodiscordant heterosexual and homosexual partners, where one partner is HIV-positive and the other HIV-negative

The consideration of utilizing emtricitabine/tenofovir as a reduction strategy involves discussion with a health professional who can help the patient navigate the benefits and risks. Patients are advised to discuss any history of bone issues, kidney issues, or hepatitis B infection with their healthcare provider.[19] Effectiveness of PrEP for prevention of infection is reliant on an individual's ability to take the medication consistently.[20]

Emtricitabine/tenofovir is also used for HIV post-exposure prophylaxis. People who start taking emtricitabine/tenofovir see HIV reduction benefits up to 72 hours after starting, but the medicine must be taken for thirty days after a high-risk sexual event to ensure HIV transmission levels are optimally reduced.[21][22]

Emtricitabine/tenofovir as PrEP should not be used for individuals who are positive for HIV-1.[7]

HIV treatment

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Emtricitabine/tenofovir has been approved in the United States as part of antiretroviral combination therapy for the treatment of HIV-1.[7] The combination therapy is suggested as one of the options for adults who have not received any prior treatment for HIV infection.[23]

Hepatitis B

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Both emtricitabine and tenofovir are indicated for the treatment of hepatitis B, with the added benefit that they can _target HIV for those with co-infection.[24] Emtricitabine/tenofovir may also be considered for some antiviral resistant hepatitis B infections.[25]

Pregnancy and breastfeeding

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In the United States, it is recommended that all pregnant HIV-infected women start antiretroviral therapy (ART) as early in pregnancy as possible to reduce the risk of transmission. ART generally does not increase risk of birth defects with exception of dolutegravir, which is not recommended during first trimester of pregnancy only due to potential risk of neural tube defects.[26]

Emtricitabine/tenofovir is secreted in breast milk.[27] In developed countries, HIV-infected mothers are generally recommended to not breastfeed due to slight risk of mother-to-children HIV transmission.[28][29] In developing countries, where avoiding breastfeeding may not be an option, the World Health Organization recommends a triple drug regimen of tenofovir, efavirenz, and either lamivudine or emtricitabine.[29]

Side effects

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Emtricitabine/tenofovir is generally well tolerated. Some of its side effects include:[7]

  • Rare: lactic acidosis, liver dysfunction, worsening of hepatitis B infection
  • Common: headache, abdominal pain, decreased weight, nausea, diarrhea, and decreased bone density

Fat redistribution and accumulation (lipodystrophy) has been observed in people receiving antiretroviral therapy, including fat reductions in the face, limbs, and buttocks and increases in visceral fat of the abdomen and accumulations in the upper back.[7] When used as pre-exposure prophylaxis (PrEP) this effect may not be present.[30] Weight changes have however been linked to the medication.[31]

Drug interactions

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Drug-drug interactions[7]
Drug-drug Interaction Coadministration
Tenofovir Didanosine
  • May increase didanosine concentration and risk of didanosine toxicity (e.g. pancreatitis, neuropathy).
  • Discontinue didanosine if patient develops didanosine-associated adverse events.
  • For patients who weigh more than 60 kg, didanosine dose should be reduced to 250 mg; there is no available data to recommend didanosine dose adjustments in patients who weigh less than 60 kg.
Atazanavir
  • May decrease atazanavir and increase tenofovir concentrations.
  • Atazanavir should only be taken together with emtricitabine/tenofovir with ritonavir.
  • Monitor for tenofovir toxicity.
Lopinavir/ritonavir, atazanavir coadministered with ritonavir & darunavir coadministered with ritonavir
  • May increase tenofovir concentrations.
Ledipasvir/sofosbuvir
  • May increase tenofovir concentrations.
  • Consider alternative Hepatitis C antiviral or antiretroviral therapy.
  • Monitor for tenofovir toxicity.
Emtricitabine/tenofovir P-glycoprotein and breast cancer resistance protein (BCRP) transporters inhibitors
  • May increase absorption of emtricitabine/tenofovir.
Drugs may decrease renal function (e.g. acyclovir, adefovir, dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, etc.)
  • May increase emtricitabine and/or tenofovir concentrations.
High-dose or multiple NSAIDs
Orlistat
  • May inhibit the absorption of emtricitabine/tenofovir and result in loss of viral control.[32]
  • Monitor HIV viral load frequently while the patient is taking orlistat.
  • Discontinue orlistat if HIV viral load increases.

Other drugs with adverse reactions include dabigatran etexilate, lamivudine, and vincristine. Dabigatran etexilate used with p-glycoprotein inducers requires monitoring of decreased levels and effects of dabigatran. Lamivudine may increase the adverse or toxic effect of emtricitabine. Vincristine used with P-glycoprotein/ABCB1 inducers can decrease the serum concentration of vincristine.[33]

Society and culture

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The patent for the drug combination is owned by Gilead Sciences in some regions. The European patent EP0915894B1[34] expired in July 2018, Gilead Sciences wished the patent to be extended, however "four rival labs—Teva, Accord Healthcare, Lupin and Mylan—had sought to have that overturned in the courts in Britain", the High Court of England and Wales invalidated Gilead's patent,[35] however the company appealed [36] and the UK referred the case to the European Court of Justice who refused to extend the patent.[37] An Irish court rejected an injunction request to prevent the launch of generic Emtricitabine/tenofovir prior to the resolution of the case.[38][39] Despite the expiration of the Gilead Sciences patent, as of 2021, there are still widespread challenges to the availability and uptake of generic PrEP throughout Europe.[40]

In 2019, Gilead Sciences challenged the validity of patents granted to the United States after 2015 for using the drug combination for HIV PrEP and post-exposure prophylaxis (PEP).[41][42][43] In July 2024, The Biden administration appealed the jury finding that ruled in favor of Gilead Sciences verdict that the U.S. government's patents are invalid.[44]

In the United States, most healthcare plans are required to cover PrEP without any copay or other cost sharing. This is due to a United States Preventive Services Task Force recommendation that gave PrEP a grade A rating. Under the Affordable Care Act, this recommendation requires all non-grandfathered private health plans to cover PrEP without cost sharing.[45][46]

In the United Kingdom, PrEP is widely available to all at-risk groups following the Department for Health and Social Care's decision to make it available across England in 2020. Wales, Scotland, and Northern Ireland made it available in 2017 and 2018.[47][48]

References

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  1. ^ a b "Emtricitabine / tenofovir Pregnancy and Breastfeeding Warnings". Drugs.com. 1 August 2018. Archived from the original on 10 October 2019. Retrieved 10 October 2019.
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  4. ^ "Truvada EPAR". European Medicines Agency. 21 February 2005. Retrieved 13 June 2024.
  5. ^ a b c d e "Truvada". Drugs.com. Archived from the original on 20 December 2016. Retrieved 12 December 2016.
  6. ^ "UK label Truvada film-coated tablets". Electronic Medicines Compendium. August 2016. Archived from the original on 20 December 2016.
  7. ^ a b c d e f g h i j k "Truvada- emtricitabine and tenofovir disoproxil fumarate tablet, film coated label". DailyMed. 18 May 2018. Archived from the original on 31 October 2019. Retrieved 31 October 2019.
  8. ^ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 160. hdl:10665/44053. ISBN 9789241547659.
  9. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. ^ "AOC asks pharma CEO why $2,000 HIV drug costs just $8 in Australia". The Independent. 17 May 2019. Retrieved 15 November 2019.
  11. ^ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  12. ^ "Emtricitabine; Tenofovir Disoproxil - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  13. ^ "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV" (PDF). AIDSinfo Clinical Guidelines. July 2019. Archived from the original (PDF) on 4 December 2016. Retrieved 30 October 2019.
  14. ^ "PrEP". Centers for Disease Control and Prevention (CDC). 17 October 2019. Archived from the original on 31 October 2019. Retrieved 31 October 2019.   This article incorporates text from this source, which is in the public domain.
  15. ^ Okwundu CI, Uthman OA, Okoromah CA (2012). "Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals". Cochrane Database Syst Rev. 7 (7): CD007189. doi:10.1002/14651858.CD007189.pub3. PMC 11324012. PMID 22786505. S2CID 35672491.
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  21. ^ Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS (September 2005). "Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis" (PDF). MMWR Recomm Rep. 54 (RR-9): 1–17. PMID 16195697.
  22. ^ Kuhar DT, Henderson DK, Struble KA, Heneine W, Thomas V, Cheever LW, et al. (September 2013). "Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis" (PDF). Infection Control and Hospital Epidemiology. 34 (9): 875–92. doi:10.1086/672271. PMID 23917901. S2CID 17032413. 20711.  This article incorporates text from this source, which is in the public domain.
  23. ^ "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV" (PDF). Archived from the original (PDF) on 4 December 2016. Retrieved 30 October 2019.
  24. ^ "Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance" (PDF). Archived from the original (PDF) on 25 January 2020. Retrieved 20 November 2019.
  25. ^ "Emtricitabine and Tenofovir Disoproxil Fumarate (Professional Patient Advice)". Drugs.com. Retrieved 31 October 2019.
  26. ^ "Brief What's New in the Guidelines Perinatal". AIDSinfo. Archived from the original on 23 October 2019. Retrieved 23 October 2019.
  27. ^ "Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States" (PDF). National Institutes of Health (NIH). Archived (PDF) from the original on 12 April 2014. Retrieved 21 October 2014.
  28. ^ "Emtricitabine / tenofovir Use During Pregnancy". Drugs.com. Retrieved 23 October 2019.
  29. ^ a b "Tenofovir". Drugs and Lactation Database (LactMed). National Library of Medicine (US). 2006. PMID 30000609. Retrieved 23 October 2019.
  30. ^ "PrEP does not raise lipids or alter body fat, safety study finds". Retrieved 16 February 2018.
  31. ^ Glidden DV, Mulligan K, McMahan V, Anderson PL, Guanira J, Chariyalertsak S, et al. (July 2018). "Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine". Clin. Infect. Dis. 67 (3): 411–419. doi:10.1093/cid/ciy083. PMC 6051460. PMID 29415175.
  32. ^ "DailyMed - XENICAL- orlistat capsule". dailymed.nlm.nih.gov. Retrieved 30 October 2019.
  33. ^ Ramanathan S, Shen G, Cheng A, Kearney BP (July 2007). "Pharmacokinetics of emtricitabine, tenofovir, and GS-9137 following coadministration of emtricitabine/tenofovir disoproxil fumarate and ritonavir-boosted GS-9137". J. Acquir. Immune Defic. Syndr. 45 (3): 274–9. doi:10.1097/QAI.0b013e318050d88c. PMID 17414929. S2CID 31756102.
  34. ^ "EP0915894B1 - NUCLEOTIDE ANALOGS". Espacenet. Retrieved 13 December 2017.
  35. ^ "U.K. Court invalidates Gilead's Truvada patent extension, allowing PrEP generics". 19 September 2018.
  36. ^ "Truvada ruling could allow cheap HIV prevention in the UK -". 19 September 2018.
  37. ^ "EU door opens for generic version of AIDS medicine Truvada".
  38. ^ "Gilead loss of generic HIV drug battle a boost for gay community". The Irish Times. Retrieved 18 May 2018.
  39. ^ "Gilead in row with generics manufacturers over HIV drug in Ireland". The Irish Times. Retrieved 30 October 2017.
  40. ^ "European PrEP programs face two big issues: How to get more people coming forward, and how to serve them if they do". 27 January 2021.
  41. ^ Rowland C (24 April 2019). "Gilead defied a government HIV patent. The Justice Department has opened a review". The Washington Post. Archived from the original on 1 November 2019. Retrieved 31 October 2019.
  42. ^ Rowland C (21 August 2019). "Gilead files challenge to government patents for HIV prevention pill". The Washington Post. Archived from the original on 1 November 2019. Retrieved 29 October 2019.
  43. ^ "Petitions to US Patent and Trademark Office on HIV PrEP Patents". Gilead Sciences (Press release). 21 August 2019. Archived from the original on 30 October 2019. Retrieved 29 October 2019.
  44. ^ Silverman E (8 July 2024). "Biden administration appeals jury finding in battle over patents for HIV prevention pills". STAT News. Retrieved 8 July 2024.
  45. ^ Keith K (2021). "New Guidance On PrEP: Support Services Must Be Covered Without Cost-Sharing | Health Affairs Forefront". Health Affairs Forefront. doi:10.1377/forefront.20210728.333084. Retrieved 4 August 2022.
  46. ^ "FAQS ABOUT AFFORDABLE CARE ACT IMPLEMENTATION PART 47" (PDF). Centers for Medicare & Medicaid Services. 19 July 2021. Retrieved 4 August 2022.
  47. ^ "HIV drug PrEP to be available across England".
  48. ^ "Free PrEP on the NHS".
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