Emtricitabine/tenofovir

Emtricitabine/tenofovir, sold under the brand name Truvada among others, is a medication used to treat and prevent HIV/AIDS.[2][3] It is a fixed-dose combination of two antiretroviral medications: tenofovir disoproxil and emtricitabine.[2] For treatment, it is used either alone or together with other antiretroviral medications.[4][5] For prevention before exposure, in those who are at high risk, it is recommended with safe sex practices.[4] It does not cure HIV/AIDS.[2] Emtricitabine/tenofovir is taken by mouth.[6]

Emtricitabine/tenofovir
Combination of
Tenofovir disoproxilNucleotide analogue reverse transcriptase inhibitor
EmtricitabineNucleoside reverse transcriptase inhibitor
Clinical data
Trade namesTruvada, Tenvir-EM, other
Other namesEmtricitabine/tenofovir disoproxil fumerate
AHFS/Drugs.comProfessional Drug Facts
MedlinePlusa612036
License data
Pregnancy
category
    Routes of
    administration    		by mouth
    ATC code
    Legal status
    Legal status
    Identifiers
    PubChem CID
    NIAID ChemDB
      (verify)

    Common side effects include headache, tiredness, trouble sleeping, abdominal pain, weight loss, and rash.[2] Serious side effects may include high blood lactate levels and enlargement of the liver.[4] Use of this medication during pregnancy does not appear to harm the baby, but has not been well studied.[1]

    Emtricitabine/tenofovir was approved for medical use in the United States in 2004.[2] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[7] In the United States, emtricitabine/tenofovir is under patent until 2020, but is available as a generic in the rest of the world.[8] The 2015 wholesale cost in the developing world is about US$6.06 to US$7.44 per month.[6] In the United States, as of 2019, the wholesale cost is about US$1,710.00 per month.[9] In Australia, this amount costs about US$8.[8]

    Medical uses

    Emtricitabine/tenofovir is used to both treat and to prevent HIV/AIDS.[2] It is a tablet taken by mouth.[6] The U.S. National Institutes of Health (NIH) recommends antiretroviral therapy (ART) for all people with HIV/AIDS.[10]

    HIV prevention

    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.[11][12][13] A Cochrane review found that both tenofovir alone, as well as the tenofovir/emtricitabine combination, decreased the risk of contracting HIV by 51%.[14] It was approved for PrEP against HIV infection in the United States in 2012.[15]

    The CDC recommends PrEP be considered for the following high-risk groups:[16]

    • 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 6 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
    • Sero-discordant 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, of hepatitis B infection with their health care provider.[17]

    People who start taking emtricitabine/tenofovir see HIV reduction benefit 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.[18][19] Effectiveness of PrEP for prevention of infection is reliant on an individual's ability to take the medication consistently.[20]

    Truvada as PrEP should not be used for individuals that are positive for HIV-1. [21]

    HIV treatment

    Emtricitabine/tenofovir has been approved in the United States as part of antiretroviral combination therapy for the treatment of HIV-1.[4] The combination therapy is suggested as one of the options for adults who have not received any prior treatment for HIV infection.[22]

    Hepatitis B

    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.[23] Emtricitabine/tenofovir may also be considered for some antiviral resistant hepatitis B infections.[24]

    Pregnancy and breastfeeding

    In the United States, it is recommend that all pregnant HIV-infected women start antiretroviral therapy (ART) as early in pregnancy as possible to reduce 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.[25]

    Emtricitabine/tenofovir is secreted in breast milk.[26] In developed countries, HIV-infected mothers are generally recommended to not breastfeed due to slight risk of mother-to-children HIV transmission.[27][28] 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.[28]

    Side effects

    Emtricitabine/tenofovir is generally well-tolerated. Some of its side effects include:[13]

    • 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.[13] When used as pre-exposure prophylaxis (PrEP) this effect may not be present.[29] Weight changes have however been linked to the medication.[30]

    Drug interactions
    Drug-drug interactions[13]
    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 60kg, didanosine dose should be reduced to 250mg; there is no available data to recommend didanosine dose adjustments in patients who weigh less than 60kg.
    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. adefovir, acyclovir, adefovir, dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, etc)
    • May increase emtricitabine and/or tenofovir concentrations.
    High-dose or multiple NSAIDs
    Orlistat
    • May inhibit absorption of emtricitabine/tenofovir and result in loss of viral control[31].
    • Monitor HIV viral load frequently while 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 require 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.[32]

    Society and culture

    Cost
    See also: Pre-exposure prophylaxis § Availability and pricing

    As of 2014, the median cost per tablet, in Namibia and South Africa, was US$0.20.[6] In Canada, emtricitabine/tenofovir cost between $800 - $1,100 per month in 2016.[33] Generic emtricitabine/tenofovir was approved by Health Canada in August 2017, with a wholesale cost of $400 per month.[34] The cost for emtricitabine/tenofovir PrEP in Ontario, Canada dropped significantly after approval in September 2017.[35]

    In the United States, as of 2016, the wholesale cost is about US$1,415.00 per month.[36] This increased in 2019 to about US$1,710.00 per month.[9] The price of emtricitabine/tenofovir in the United States has been criticized by activists, who argued in a 2018 The New York Times opinion piece that the high cost keeps the drug out of reach for millions, thus harming efforts to reduce new HIV infections.[37] The Gilead CEO defended the high price at a U.S. House of Representatives committee hearing.[38] Generic emtricitabine/tenofovir was approved in the United States in 2018,[39] and it is scheduled to be released by Teva in September 2020.[40]

    Emtricitabine/tenofovir can be dispensed by trained pharmacists in California, without a prescription, for a maximum of 60 days.[41][42][43]

    Patent status

    The patent for the drug combination is owned by Gilead Sciences in some regions. The European patent EP0915894B1[44] was due to expire in July 2017, however a case is due before the European Court of Justice seeking to extend the patent.[45] An Irish court rejected an injunction request to prevent the launch of generic Emtricitabine/tenofovir prior to the resolution of the case.[46]

    In 2019, Gilead Sciences challenged patents held by the United States for the drug combination.[47][48][49]

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