Reviewed by: HU Medical Review Board | Last reviewed: March 2023

Atripla is a combination medication that contains efavirenz, emtricitabine, and tenofovir disoproxil fumarate. It can be used alone or with other antiretroviral agents as a part of antiretroviral therapy (ART) for HIV-1 in individuals who are at least 12 years of age and weigh at least 88 pounds (40 kg).

Although it is not a cure for HIV, when taken as directed, it allows for the virus to be suppressed. This prevents further transmission of HIV and allows an individual’s immune system to improve through increasing CD4 cell counts and decreasing the amount of active virus in the blood (viral load).

What are the ingredients in Atripla?

The main ingredients in Atripla are efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), while emtricitabine, and tenofovir disoproxil fumarate are nucleoside reverse transcriptase inhibitors (NRTIs).

How does Atripla work?

Atripla is a combination of two NRTI medications and one NNRTI medication. Both types of drugs stop the reverse transcription step of the HIV life cycle. Normally, HIV uses its reverse transcriptase enzyme to build a strand of DNA from its original RNA form. In order to do this, it uses genetic building blocks called nucleosides that come from the host cell. These nucleosides are strung together one at a time, like beads on a string, to create the final DNA product.

How do NRTIs work?

NRTIs act as nucleoside mimics that stop the DNA-building process. NRTIs look like normal nucleosides, except they’re missing a special chemical group on one side. Without this group, the reverse transcriptase enzyme is unable to attach more nucleosides to the chain after them.

How do NNRTIs work?

NNRTIs bind to the reverse transcriptase enzyme itself to stop the DNA-building process. When an NNRTI binds to reverse transcriptase, the enzyme is unable to attach more nucleosides to the chain. Both of these mechanisms block the full string of DNA from being formed, preventing HIV RNA from making it all the way through the reverse transcription process and into host DNA for further replication.

Possible side effects

Taking Atripla at bedtime may help with some side effects. The most common side effects of Atripla include:

  • Nausea
  • Diarrhea
  • Dizziness
  • Depression
  • Insomnia
  • Abnormal dreams
  • Fatigue
  • Headache
  • Rash
  • Nervous system symptoms

These are not all the possible side effects of Atripla. Talk to your doctor about what to expect when taking Atripla. You also should call your doctor if you have any changes that concern you when taking Atripla.

Things to note

Atripla has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because of the possibility of serious side effects as described below.

As with any medication, there are several very rare but serious risks that need to be considered before taking Atripla. Your healthcare provider can help determine what issues you may be at risk for and help determine what treatment options are the safest for you. It’s also important to remember that the risk of one or more of these issues occurring is low, and the benefits of treating the virus often greatly outweigh the risks.

Several of these rare but serious side effects of Atripla include liver issues and an increase of lactic acid in the blood (lactic acidosis). Signs of liver issues include, but are not limited to:

  • Dark-colored urine
  • Loss of appetite
  • Nausea
  • Yellowing of the whites of the eyes or skin
  • Light-colored bowel movements
  • Pain or tenderness on the right side of your stomach

Signs of lactic acidosis include, but are not limited to:

  • Trouble breathing
  • Feeling cold, especially in the limbs
  • Dizziness or lightheadedness
  • Feeling tired or weak
  • Muscle pain
  • Nausea and vomiting
  • Irregular or fast heartbeat

If you have hepatitis B virus and start taking Atripla, your hepatitis B may get worse. Atripla may also cause new or worsening kidney issues. This includes an increased risk of kidney failure. Your healthcare provider will need to monitor your kidney function before you start and while taking Atripla. Bone issues may also happen while taking Atripla, including, but not limited to, bone pain, thinning, or softening. These problems may lead to bone fractures.

One of Atripla's active ingredients, tenofovir disoproxil fumarate, can cause a bone condition called osteomalacia, along with a problem in the kidneys called proximal renal tubulopathy. Symptoms of these health issues include bone pain, pain in the limbs, fractures, joint pain, weakness, and muscle pain. If you are at risk for kidney problems, and you experience ongoing or worsening symptoms related to your bones or muscles, it's important to get checked for low levels of phosphorus in your body and the presence of osteomalacia.

Rarely, serious psychiatric issues such as depression, angry behavior, or strange thoughts may occur in some individuals. Contact your healthcare provider as soon as possible if you experience any of these or any suicidal thoughts or ideations. These are not all the possible side effects of Atripla. Patients should talk to their doctor about what to expect with treatment with Atripla.

Before starting Atripla, tell your doctor if you:

  • Have or previously had hepatitis B virus
  • Have or previously had hepatitis C virus
  • Have a history of liver, heart, or kidney problems
  • Have a history of bone problems
  • Have a history of mental illness
  • Have a history of seizures
  • Are using drugs or alcohol or have a history of drug or alcohol abuse
  • Are pregnant or planning to become pregnant
  • Are breastfeeding or planning to breastfeed
  • Are taking any over-the-counter vitamins, supplements, medicines, or herbal remedies
  • Are on any other medications or are about to start any other medications, including hormonal birth control, seizure medications, or medications for hepatitis viruses

There are several medications that cannot be taken with Atripla, including medications called voriconazole, elbasvir, or grazoprevir. It is important to tell your doctor about any and all medications you are taking to ensure you are taking Atripla safely.

Atripla may cause a condition called IRIS (immune reconstitution inflammatory syndrome). IRIS occurs when an individual’s immune system gets stronger after being weak and responds aggressively to previously hidden infections. This heightened response may make the person fighting the infection feel worse. Alert your healthcare provider immediately if you begin to have new symptoms after taking Atripla. Atripla may also cause changes in body fat, especially around the breast, trunk, upper back, and neck regions. Rash, nerve issues, and seizures are other possible side effects of Atripla.

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