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IRIS in HIV: 7 Facts To Know

Medically reviewed by Marie Dorsey, PharmD, AAHIVP
Posted on August 28, 2023

If you’re starting treatment for the human immunodeficiency virus (HIV), you should know about the immune reconstitution inflammatory syndrome (IRIS). IRIS is a potential complication that can develop in people shortly after starting an HIV treatment and can cause unpleasant symptoms including pain, fever, breathing difficulties, vision problems, and others.

Even though IRIS can make you feel temporarily unwell, developing it usually means your immune system is getting stronger. Following are seven facts you should know about IRIS if you or a loved one are starting a new HIV treatment.

1. IRIS Is a Potential Complication of HIV Treatment

IRIS is an inflammatory response to starting or changing HIV treatment with antiretroviral therapy (ART) — also known as highly active antiretroviral therapy (HAART) or combination antiretroviral therapy. The treatment is generally taken as one pill that contains multiple drugs. Up to 1 in 3 people who begin ART develop IRIS. When IRIS occurs, it usually develops within the first four to eight weeks of starting antiretroviral treatment.

IRIS can occur when the HIV treatment effectively reduces a person’s HIV viral load and their immune system is getting stronger. When your immune system gets stronger, it can start to fight an infection that it couldn’t fight previously. Sometimes, this can make you feel sicker, even though your HIV treatment is working.

IRIS can also occur in people who don’t have HIV, such as people who’ve undergone organ transplants, given birth, or have chronic inflammatory conditions.

2. IRIS May Make You Feel Sick, Even Though Your HIV Infection Is Improving

The goals of ART are to reduce the amount of virus in your body and restore your immune system. As the medication starts to work, your immune system should get stronger.

Your immune function is often measured by your CD4-positive T-cell (CD4) count. People without HIV typically have a CD4 count between 500 and 1,500 cells per cubic millimeter.

If you have HIV and don’t get treatment, your CD4 count will decrease. A lower CD4 count means a weaker immune system. A CD4 count below 200 cells per cubic millimeter puts you at risk of developing infections that don’t usually occur in healthy people, known as opportunistic infections. If your CD4 count is too low, you may not know you have an infection because your immune system isn’t strong enough to recognize and react to it. As such, you won’t have any symptoms of the infection. Left untreated, an infection may become worse and cause permanent damage to your body.

After you begin HIV treatment, your CD4 count should begin to increase gradually. As your immune system gets stronger, it will start to recognize that you have an infection. Once your immune system knows about the infection, you may begin to develop symptoms of that infection.

3. There Are Two Types of IRIS — Paradoxical and Unmasking

In paradoxical IRIS, you may experience returning or worsening symptoms of an infection you’ve already been diagnosed and treated for. Your symptoms will likely be similar to those you experienced in the past. This type of IRIS is known as “paradoxical” because it doesn’t make sense to be sick with a disease you’ve already been treated for. However, if you were treated for an infection while your immune system was very weak, you may not have been cured. When your immune system gets stronger, it will start to fight the infection again.

In unmasking IRIS, you can get new symptoms for an infection you weren’t diagnosed with. As your immune system gets stronger, it “unmasks” the symptoms of an infection you didn’t know you had.

4. IRIS Symptoms Depend on Which Germs Are in Your Body

Most people who develop IRIS have mild to moderate symptoms such as pain and fever. Your specific symptoms will depend on the type of germ causing the infection.

People with HIV may be more likely to be infected by some germs (such as a virus, bacteria, fungi, or parasites). HIV can damage your immune response to infections. The infections that occur more often or cause more severe illness in people with weakened immune systems are known as opportunistic infections.

You may have breathing difficulties, a cough, or shortness of breath if you have an infection in your airways or lungs. Opportunistic infections that can cause breathing problems include:

  • Bacteria, such as tuberculosis or mycobacterium avium complex
  • Viruses, such as herpes simplex virus
  • Fungi, such as candidiasis (yeast), coccidioidomycosis (valley fever), cryptococcus, histoplasmosis, or pneumocystis pneumonia

An infection in your central nervous system (brain or spinal cord) can cause serious symptoms, such as confusion, problems speaking, loss of muscle control, and paralysis. In people with HIV/AIDS, this type of infection can be caused by a virus called the John Cunningham virus, which causes a disease called progressive multifocal leukoencephalopathy (PML). More commonly diagnosed is toxoplasmosis, caused by the Toxoplasma gondii parasite, which can infect the brain and several other organs. The cryptococcus fungus can also cause central nervous system infections.

You might experience vision problems if you have cytomegalovirus (CMV) retinitis, a viral infection of the eye. People with CMV retinitis have difficulty with vision that worsens over time. CMV retinitis is a medical emergency — if not treated promptly, it can cause blindness.

You can develop painless, pink- or purple-colored spots — raised or flat — on your legs, feet, or face if you’re infected by a virus called human herpesvirus 8 (HHV-8). These lesions may also develop on internal organs and can result in significant illness. HH8 can also cause a type of cancer called Kaposi’s sarcoma in people with very weak immune systems.

You may experience other symptoms caused by other types of infectious diseases. Talk to your doctor right away if you notice any abnormal symptoms after starting HIV medications, as you may need treatment for specific IRIS-related infections.

If your infection isn’t treated, you may have serious complications, such as respiratory (breathing) failure, cancer, or blindness. People with infections that affect their brain and spinal cord may have an increased risk of death.

5. IRIS Is More Likely in People With a Low CD4 Count When They Start ART

People with low CD4 counts — usually less than 100 cells per cubic millimeter — are more likely to develop IRIS when starting ART than people with CD4 counts over 200 cells per cubic millimeter.

Other risk factors for developing IRIS include:

  • Starting ART at a younger age
  • Being male
  • Having a strong response to ART such that your CD4 count quickly increases and your viral load quickly decreases
  • Having an opportunistic infection before starting ART
  • Starting ART treatment within 30 days of completing treatment for an opportunistic infection
  • Having certain genetic factors

Talk to your health care provider about your risk factors for developing IRIS before you start your treatment. If you have an opportunistic infection, your doctor may prescribe additional treatment or testing before you start ART.

6. You’ll Likely Keep Taking ART if You Develop IRIS

If you develop IRIS and begin feeling sick after starting ART, your doctor likely won’t have you stop the treatment. Continuing with it will help your immune system to get stronger so it can help fight the infection causing your unpleasant symptoms.

However, your doctor may temporarily stop your HIV treatment if you have life-threatening symptoms. Never stop your medication without asking your doctor first.

7. There’s No Specific Treatment for IRIS

There isn’t one specific treatment for IRIS. Your treatment will focus on getting rid of the infection and relieving your symptoms. Opportunistic infections are treated with antibiotics, antivirals, or antifungals, depending on the type of germ.

Mild symptoms, like pain and fever, can be managed with over-the-counter pain relievers like acetaminophen (Tylenol) or ibuprofen (Motrin or Advil).

If you have significant inflammation that causes severe lung disease or problems with your central nervous system, you may need anti-inflammatory medications called corticosteroids.

If you begin to feel unwell in the first few months after starting ART for HIV, talk to your doctor right away.

Talk With Others Who Understand

On myHIVteam, the social network for people with HIV and their loved ones, more than 37,000 members come together to ask questions, give advice, and share their stories with others who understand life with HIV.

Did you develop IRIS when you started or changed HIV treatment? How did you manage your symptoms? Share your experience in the comments below, or start a conversation by posting on your Activities page.

Posted on August 28, 2023
All updates must be accompanied by text or a picture.

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Marie Dorsey, PharmD, AAHIVP is currently a clinical pharmacist at Bridgewell Medical, specializing in medication therapy management and holds a certification as an HIV pharmacist through the American Academy of HIV Medicine. Learn more about her here
Amanda Jacot, PharmD earned a Bachelor of Science in biology from the University of Texas at Austin in 2009 and a Doctor of Pharmacy from the University of Texas College of Pharmacy in 2014. Learn more about her here

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