What to Know About Atripla (Efavirenz, Emtricitabine, Tenofovir DF)

First 3-in-1 Antiretroviral Tablet Used Treat HIV

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Atripla is a single-pill, fixed-dose combination drug used to treat HIV in adults and older children. Approved for use by the U.S. Food and Drug Administration (FDA) in 2004, Atripla was the first all-in-one antiretroviral drug that required only one pill daily to achieve complete viral suppression.

Atripla contains three different antiretroviral drugs:

  • Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI) also sold as a single-drug tablet called Sustiva
  • Emtricitabine, a nucleoside reverse transcriptase inhibitor (NRTI) also known as FTC, available in a single-drug capsule called Emtriva
  • Tenofovir disoproxil fumarate (TDF), another NRTI also sold as a single-pill tablet called Viread
Atripla pills spilling out of a pill bottle
NIAID / Flickr / CC BY 2.0

Until 2015, Atripla was given preferred, first-line status in the treatment of HIV in the United States. With the introduction of integrase inhibitors, a newer class of drugs that offered greater durability and fewer side effects, Atripla is now classified as an alternative drug for first-line antiretroviral therapy.

Atripla does not cure HIV but rather suppresses the virus to undetectable levels, thereby preventing disease progression. The drugs in Atripla do so by blocking the enzyme reverse transcriptase that HIV needs to replicate.

There are no generic versions of Atripla, although patent exclusivity for the drug is set to expire in 2024.


Atripla is used to treat HIV infection in adults and children 12 and over. Because Atripla's dose is fixed and cannot be modified, it is not used in smaller children due to the risk of toxicity.

Atripla is less commonly used in first-line therapy, unless you are unable to take the preferred first-line options. It more commonly used in subsequent therapies if there has been a treatment failure.

When introduced in 2004, Atripla was considered a game-changer given that antiretroviral therapies of the time often required multiple drugs with different dosing schedules. The convenience of a once-daily, single-pill formulation has been shown to improve adherence and increase rates of viral suppression compared to multi-pill regimens.

A 2016 study from the South Carolina Medicaid program reported that once-daily, single-pill antiretroviral therapies not only improved viral suppression rates by 24% but also led to a 29% reduction in hospitalizations.

There are no off-label uses for Atripla.

Before Taking

Whether you are newly infected with HIV or changing treatment, your healthcare provider will order tests to "profile" your virus. These tests help your healthcare provider determine which drugs will work best for you based on the types and number of drug-resistant mutations your virus has.

Even if you have been newly infected, it is possible to pick up a drug-resistant virus through sex, shared needles, or other modes of transmission (referred to as transmitted resistance). Drug resistance can also develop naturally over time when exposed to HIV drugs.

There are two blood tests commonly used to profile your virus:

  • Genetic resistance testing, also known as genotyping, is the preferred option that detects the number and types of mutations that confer resistance.
  • Phenotypic testing, typically used with genotyping in people with treatment failure, directly exposes the virus to all available antiretroviral drugs to see which ones work best.

Precautions and Contraindications

Atripla is contraindicated for use in people with a prior hypersensitive reaction to efavirenz, emtricitabine, or tenofovir.

There are other conditions in which Atripla is avoided or used with caution:

  • Kidney disease: Atripla is excreted in part through the kidneys and needs to be used with caution in people with kidney disease. It should never be used in those with a creatinine clearance of less than 50 milliliters per minute (mL/min), an indication of impaired kidney function.
  • Liver disease: Atripla is not recommended for people with moderate to severe liver impairment, as measured by a Child-Pugh score of 2 and 3, respectively. This typically includes people with cirrhosis and many with chronic hepatitis C infection.
  • Psychiatric conditions: The drug efavirenz used in Atripla can exert a potent effect on the central nervous system (CNS) and should be avoided in people with psychiatric conditions as it may provoke manic, paranoid, or depressive behaviors.
  • Osteoporosis: Tenofovir can cause bone mineral loss. Although this is not a problem for most people, those with significant osteoporosis or a history of pathologic fractures should undergo bone mineral density (BMD) tests to see if the drug is appropriate for them.
  • Pregnancy: Animal studies on Atripla have shown significant evidence of fetal harm. The efavirenz component of Atripla is associated with an increased risk of birth defects and is typically avoided during the first trimester of pregnancy. If you are pregnant or planning to be, speak with your healthcare provider to better understand the benefits and risks of Atripla before starting treatment. If you become pregnant while on Atripla, you will typically be switched to another therapy with a lesser risk of birth defects.

Because Atripla can cause liver and kidney problems even in people with no prior history of liver or kidney disease, routine monitoring of liver enzymes and kidney function is considered essential.

Other Combination Antiretroviral Drugs

In addition to Atripla, there are 12 other combination drugs that can be taken on their own with a once-daily dose:

In January 2021, the FDA approved the first once-monthly antiretroviral combination therapy, called Cabenuva, which is comprised of two separate injections of the drugs cabotegravir and rilpivirine. This medication can now be given every two months.


Atripla is a co-formulated tablet comprised of 600 milligrams (mg) of efavirenz, 200 mg emtricitabine, and 300 mg tenofovir disoproxil fumarate. The pink, oblong tablet is film-coated and embossed on one side with the number "123."

For adults and children 12 years or older who weigh at least 88 pounds (40 kilograms), the recommended dose of Atripla is one tablet taken daily on an empty stomach.

If a person weighs less than 88 pounds, another combination therapy would need to be considered.


In people treated for tuberculosis (an opportunistic infection commonly seen in people with HIV), the Atripla dose would need to be supplemented if the drug rifampin is used. In such instances, an additional 200 mg of efavirenz in the form of Sustiva would be taken until the completion of tuberculosis therapy.

Rifampin is sold under the brand names Rifadin, Rimactane, and others.

How to Take and Store

Because efavirenz can exert significant CNS effects (see "Side Effects" below), Atripla is best taken at bedtime so that you can sleep through most of them.

Food or No Food?

Some people find that taking food with Atripla reduces the CNS side effects, but this is generally not recommended. If you take Atripla with food, avoid high-fat meals as fat increases the absorption of both efavirenz and tenofovir DF and may increase rather than decrease side effects.

Atripla is best stored at room temperature in its original light-resistant container, ideally between 68 to 77 degrees F (20 to 25 degrees C). Avoid prolonged exposure to heat, such as storing the pills in your glove compartment or on a windowsill. Keep track of the expiration date, and dispose of any expired drugs.

Atripla should not be swallowed whole. Avoid chewing, splitting, or crushing the tablet as that can affect drug absorption.

If you miss a dose, take it as soon as you remember. If it is near the time of your next dose, skip the original dose and continue as normal. Never double up doses as this can increase the risk of side effects and toxicity.

Side Effects

Each of the drugs contained in Atripla can cause side effects. With efavirenz, the most prominent side effects are those affecting the central nervous system. NRTI drugs like tenofovir and emtricitabine are known to cause mitochondrial toxicity, in which injury to the energy units in cells (called mitochondria) can cause a range of long-term side effects and complications.


The side effects of Atripla tend to mild and transient, gradually subsiding over the course of days or weeks as the body adapts to treatment.

With that said, some people can experience profound CNS effects due to efavirenz, which make take weeks to overcome. In some cases, the effects can be so persistent or severe as to require a change in treatment.

According to premarket clinical studies, around 4% of people stopped Atripla due to intolerable side effects within a year.

The most common side effects of Atripla include:

  • Nausea (9%)
  • Diarrhea (9%)
  • Fatigue (9%)
  • Depression (9%)
  • Sinusitis (8%)
  • Dizziness (8%)
  • Upper respiratory infection (8%)
  • Rash (7%)
  • Headache (6%)
  • Runny nose and congestion (5%)
  • Insomnia (5%)
  • Anxiety (5%)
  • Abnormal or vivid dreams (2%)
  • Vomiting (2%)

Always let your healthcare provider know about any side effects you experience while taking Atripla, particularly if they persist or worsen.


In rare instances, Atripla can cause severe and even life-threatening side effects. Some of this can occur during the early stages of treatment, but most tend to develop with ongoing use due to increased mitochondrial damage.

Serious complications associated with Atripla include:

  • Hepatitis B exacerbation: Symptoms include fatigue, nausea, vomiting, abdominal swelling, dark urine, and jaundice (yellowing of the eyes and/or skin).
  • Hepatomegaly with steatosis: Liver toxicity due to NRTIs can manifest with an enlarged liver (hepatomegaly) alongside fatty changes in the liver (steatosis).
  • Hypersensitive reactions: Rash outbreaks are not uncommon when first starting efavirenz but are usually mild and self-limiting. In rare instances, a rash can be severe and require the immediate termination of treatment.
  • Kidney failure: Tenofovir DF is associated with an increased risk of kidney impairment, some cases of which have led to acute renal failure. Once treatment is stopped, kidney function is usually restored.
  • Lactic acidosis: NRTIs like tenofovir and emtricitabine can cause the potentially life-threatening build-up of lactic acid in the bloodstream.
  • Psychiatric events: Premarket studies reported serious psychiatric side effects, while uncommon, included suicidal thoughts (0.7%), paranoia (0.4%), and manic behaviors (0.2%).

Warnings and Interactions

Atripla carries a black box warning advising consumers of the risk of a potentially severe flare-up of hepatitis symptoms in people coinfected with hepatitis B if treatment is stopped. This is related to the drug tenofovir. If Atripla is stopped, liver function should be monitored and anti-hepatitis B treatment should be started if a flare-up occurs. (Hepatitis B testing is recommended prior to starting therapy to check for infection.)

The black box warning also advises about the risk of lactic acidosis and hepatomegaly with steatosis, both of which may be serious and (with lactic acidosis especially) potentially deadly.

Drug Interactions

There are a number of drug interactions associated with Atripla. Among them, the antifungal drug Vfend (voriconazole) is contraindicated for use, as Atripla can reduce the effectiveness of antifungal therapy.

Some of the other more significant interactions include:

  • Calcium channel blockers: Orap (pimozide), Propulsid (cisapride), Vascor (bepridil), and others
  • Ergot derivatives: DHE 45 (dihydroergotamine) , Ergostat (ergotamine), Ergotrate (methylergonovine), and others
  • Hepatitis B medication: Hepsera (adefovir)
  • Methadone
  • St. John's wort
  • Tuberculosis drugs: Mycobutin (rifabutin), Rifadin (rifampin), and others
10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.