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HIV Drug Resistance: Mutations, Testing, Symptoms, and More

Updated on April 1, 2024

If you or a loved one is taking antiretroviral therapy (ART) for HIV, you’ve probably heard about the possibility of HIV drug resistance. Developing HIV drug resistance means that the drugs that used to control your HIV may no longer work.

“Currently I am resistant to 70 percent of the HIV regimens,” one myHIVteam member wrote. “Luckily I have a very good doctor who found something that works for me. He helped me to stay undetectable for the last five years. There is always hope.”

Another member wrote, “I’ve never had resistance, but I have taken care of friends who have gone through it. Normal everyday tasks become impossible.”

Continue reading to learn more about how HIV drug resistance develops, how it’s detected, and what you can do about it.

What Is Antiretroviral Therapy?

Antiretroviral therapy is the treatment recommended for everyone living with HIV. While ART isn’t a cure for HIV, it can help control HIV and prevent transmission to others. Taking ART helps to reduce your viral load — the amount of HIV in your body — by preventing the virus from replicating (making copies of itself).

The U.S. Food and Drug Administration (FDA) has approved more than 30 medications for treating HIV infection. When you’re taking ART, you will take a combination of different HIV medications every day. These drugs are grouped into seven different drug classes based on the way they stop HIV replication, including:

  • Nucleoside reverse transcriptase inhibitors (NRTIs)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  • Protease inhibitors (PIs)
  • Fusion inhibitors
  • CCR5 antagonists
  • Integrase strand transfer inhibitors (INSTIs)
  • Post-attachment inhibitors

Most people take ART as a pill or liquid that’s swallowed by mouth one or more times each day. More recently, people with HIV have gotten access to treatment regimens that are available as injections they get at the doctor’s office. Injections may occur from every two weeks to every six months, depending on the type of medication.

Your HIV care team will help you choose the best treatment regimen for you based on your needs, side effects, and potential drug interactions.

How Does HIV Drug Resistance Develop?

HIV drug resistance happens when mutations (changes) in the virus cause it to become resistant to a drug that used to work. Mutations may occur every time HIV replicates, and HIV drugs may not recognize the new version of the virus. When HIV drugs can’t recognize the virus, the virus is able to continue replicating and cause more damage to the immune system.

You can have HIV drug resistance to just one HIV drug or multiple HIV drugs based on the mutations in the virus. For example, mutations in proteins needed for replication called nucleoside reverse transcriptases, can cause resistance to NRTIs like emtricitabine (Emtriva) or lamivudine (Epivir). If the virus has mutations in other proteins involved in other parts of the virus life cycle, you may be resistant to other HIV drugs.

People can develop drug resistance more easily to some HIV drugs than others. For example, just one mutation in the protein that NNRTIs target can result in NNRTI drug resistance. However, it takes several mutations to develop resistance to other HIV drugs, like protease inhibitors.

Some mutations increase a person’s chances of developing resistance to more than one HIV drug. When a mutant strain of HIV is resistant to more than one HIV drug, it’s known as cross-resistance. This means fewer drugs can be used to treat the virus. Similarly, as more mutations develop, there are fewer options for treatment.

There are three types of HIV drug resistance, based on how the drug resistance developed:

  • Transmitted
  • Pretreatment
  • Acquired drug resistance

Transmitted HIV Drug Resistance

Transmitted drug resistance happens when a drug-resistant strain of HIV is transmitted (spread) from one person to another. This type of drug resistance can occur in people who haven’t yet begun HIV treatment.

Overall transmitted drug resistance in the United States ranges from 11 percent to 15 percent, depending on the drug class.

Pretreatment HIV Drug Resistance

Pretreatment HIV drug resistance is another type of drug resistance that can be found in people who haven’t begun HIV treatment but have been exposed to HIV medications before they were infected with HIV.

The World Health Organization (WHO) estimates that about 10 percent of adults starting ART for HIV have a strain of the virus that’s already resistant to NNRTIs. NNRTI resistance is up to three times more common in people with previous HIV medication exposure.

People who may be exposed to HIV medications include people taking preexposure prophylaxis (PrEP) and babies born to a parent taking HIV medications to prevent transmission from parent to child (perinatal transmission). It’s very rare to develop pretreatment HIV drug resistance from PrEP. According to the WHO, almost half of babies diagnosed with HIV in sub-Saharan Africa already have NNRTI resistance before they start treatment due to exposure to HIV medication within the womb.

Acquired HIV Drug Resistance

Acquired HIV drug resistance occurs when a person taking ART develops a drug-resistant HIV strain. The person’s HIV continues to replicate, despite their taking ART — a phenomenon called virologic failure. Researchers have found that at least 70 percent to 80 percent of people with virologic failure have acquired resistance to HIV drugs, according to the International Association of Providers of AIDS Care.

Although rare, a person can develop acquired resistance when taking their medication just as prescribed. More commonly though, this type of resistance happens when people don’t stick to their medication regimen or don’t take their medications as prescribed. When a person misses doses, the virus replicates and mutations may develop. If too many mutations develop, you may need to change ART medications.

Keep in mind, drug resistance is usually not an issue in people with undetectable viral loads (achieved by taking medications consistently and as prescribed).

How Do You Test for HIV Drug Resistance?

HIV drug resistance testing can help you and your HIV care team identify which HIV drugs won’t be effective against the strain of HIV you’re infected with. It’s possible to test for resistance to several HIV drugs, including NRTIs, NNRTIs, PIs, and INSTIs.

Your health care provider may order HIV drug resistance testing in several situations, including:

  • When you’re first diagnosed with HIV
  • If you experience virologic failure during your treatment
  • If your viral load is higher than expected
  • If you become pregnant
  • If you’re planning on changing your treatment regimen

There are two types of HIV drug resistance tests — genotypic and phenotypic testing. Genotypic tests look for mutations in the genes related to drug resistance. Phenotypic tests measure how well the virus can replicate when it is exposed to an HIV drug.

The type of testing you receive depends on the reason for testing. For example, genotypic testing is preferred in people newly diagnosed with HIV and is much more common. Phenotypic testing may be preferred in people with known or suspected HIV drug resistance. Phenotypic testing is rather rare and is only used in high-level resistance or more difficult situations where genotypic testing doesn’t provide the information needed.

What Are the Symptoms of HIV Drug Resistance?

You may not notice any symptoms of HIV drug resistance right away. It is therefore crucial you get your labs drawn when your provider recommends it. Your lab results will likely reveal drug resistance far before you would experience symptoms.

As the virus continues to replicate, your immune system may become weaker and less able to fight off infection, making you prone to opportunistic infections. You may notice symptoms of these infections, according to Mayo Clinic, such as:

  • Fever or chills
  • Extreme tiredness
  • Headache
  • Swollen lymph glands
  • Diarrhea
  • Weight loss
  • Oral thrush (yeast infection in your mouth)
  • Cold sores
  • Shingles (painful, itchy rash on one side of your face or body)
  • Cough
  • Difficulty breathing

Talk to your health care provider right away if you notice any new or worsening symptoms.

Can You Prevent HIV Drug Resistance?

The best way to reduce your risk of HIV drug resistance is to stick to your treatment regimen — also known as medication adherence. If you don’t take your HIV medication exactly as prescribed, consistently and on time, it gives the virus an opportunity to replicate and develop mutations. Having good medication adherence means you can keep your viral load undetectable and will help to prevent drug-resistant viruses from developing.

Following are some tips to help you take your HIV medication on time, every time and prevent resistance:

  • Use a seven-day pill box.
  • Keep your pills in a place where you’ll notice them. Make sure to choose a cool, dry place and avoid exposing the medication to extreme temperatures.
  • Set an alarm for dosing times.
  • Ask friends and family to help you remember.
  • Make taking your pills part of your daily routine.
  • Use a calendar to track refills.
  • Get your refills before you run out of medicine.
  • Take a backup supply of medication for unexpected events.
  • Consider food requirements and follow them.
  • Know which medicines can and cannot be taken together. Some medicines can make your HIV medication less effective and can result in treatment failure.
  • Keep all your appointments with your HIV care team.
  • Get all labs drawn on time.
  • Report any side effects or symptoms to your doctor so they may be addressed promptly.

Talk to your HIV care team about your risk of HIV drug resistance, how to get tested, and what you can do to prevent it.

Connect With Others Who Understand

On myHIVteam, the social network for people with HIV and their loved ones, more than 40,000 members come together to ask questions, give advice, and share their stories with others who understand life with HIV.

Have you had HIV resistance testing? If so, how did your treatment change? Share your experience in the comments below, or start a conversation by posting on your Activities page.

    Updated on April 1, 2024
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    Marie Dorsey, Pharm.D., BCPS, 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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