HIV Drug Resistance: What to Know

Medically Reviewed by Jonathan E. Kaplan, MD on April 15, 2022
6 min read

HIV drug resistance can happen if the HIV virus in your body changes form, or mutates. This will affect how well your antiretroviral therapy (ART) works. Medications that are used to control your HIV will no longer be effective. The HIV in your body will then begin to multiply. This can make you more likely to spread HIV and lead to a worsened condition.

As of 2020, 27.5 million people were on ART out of the nearly 37.7 million people worldwide with HIV.

With more people on HIV medications, there’s been a rise in HIV drug resistance as well. All antiretroviral drugs can potentially become fully or partly ineffective.

One way this happens is through “acquired HIV drug resistance.” This is when the virus is allowed to replicate (make copies of itself) while you are taking, or only partially taking, your antiretroviral medication.

This can happen if you don’t stick to your HIV medication routine. But it can also happen if your body doesn’t absorb the drugs properly or if interactions with other drugs you are taking make the HIV drugs less effective. In these cases, the HIV may mutate into a form that affects your medication’s ability to fight the virus.

You can also start with a virus that was already drug resistant when it was transmitted to you by another person. Experts call this “transmitted HIV drug resistance.” This means that even though you have never been on antiretroviral medications before, your HIV is already resistant to certain HIV medications. Transmitted drug resistance happens in about 12 to 24 percent of people with newly diagnosed HIV in the United States.

Another form is “pretreatment HIV drug resistance.” This can happen if you’re exposed to HIV medications at the time you become infected with HIV, such that the virus becomes drug-resistant before you are able to start treatment. This is unusual, but examples include:

  • If a mother takes medications to prevent mother-to-child transmission of HIV, but the baby becomes infected anyway.
  • You become infected while you are taking pre-exposure prophylaxis (PrEP) to prevent HIV.

The type of drug resistance you have will depend on the drug-resistance mutations in your HIV virus. Examples of this include:

  • If you have a protease mutation or mutations (there are several), your HIV may be resistant or partially resistant to protease inhibitor medications. Drugs such as darunavir (Prezista) might not work for you.
  • If you have a reverse transcriptase mutation, you might be resistant to reverse transcriptase inhibitors, such as emtricitabine/TDF (Truvada) or efavirenz (Sustiva).

HIV drugs that are in the same class stop the replication of HIV in the same way. This means if you become resistant to one drug in a certain class, you might be fully or partly resistant to other drugs in that same class.

Drug resistance testing requires taking a sample of your blood. There are two kinds of tests:

Genotype testing. These find drug resistance mutations in the genes of HIV. These tests look at the reverse transcriptase (RT), protease (PR), and integrase (IN) genes. The tests check to see if there are mutations that are common in drug resistance. Everyone with HIV should have this type of testing before they begin treatment. In some special cases (like if you’re pregnant with HIV or you just became infected with HIV) it’s important to start treatment right away rather than wait for a genotype test.

Phenotype testing. This test measures the ability of your HIV to replicate in different concentrations of antiretroviral drugs. Usually, you’ll have this test done if you’ve been on treatment and have trickier drug resistance patterns.

Once you’re on an HIV treatment regimen, you’ll routinely take a viral load test. This test will tell you if your current medications are working to control your HIV.  Depending on how high your viral load was to start with, it may take a few months for the drugs to completely suppress your virus.

If you continue to have a detectable viral load after a few months, it doesn’t necessarily mean that your treatment plan is ineffective. The first thing to know (and which your doctor will ask) is if you are taking your HIV drugs daily as prescribed. If you’re not, your doctor will work with you to try to fix this problem.  Maybe there is something in your daily life that interferes with taking the medicine, or maybe there is a side effect that is keeping you from taking the medication. Your doctor will want to repeat the viral load test when you are taking the medicine every day. 

If you are taking your medicine correctly, a low level of virus could be a “viral load blip,” which is a temporary jump in the amount of HIV in your blood. Continue to take your medication and your viral load should go back to undetectable. A low level of virus could also be caused by an interaction with another drug you are taking. Your doctor will try to fix that.

If your tests continue to show that your treatment plan isn’t successful, your doctor will do a drug resistance test, starting with a genotype test. Your doctor may choose to do drug resistance testing if:

  • Your viral load jumps above 1,000 copies/mL.
  • Your treatment plan won’t lower your viral load as quickly as it’s supposed to.

The results from the drug resistance test will let you know if drug resistance is the reason why your treatment is ineffective. If this is the case, the results from the test will help your care team find a new treatment for you.

If you have HIV, you should stay on your treatment plan and continue to take your medications as your doctor tells you. This can help you avoid drug resistance.

To stick to your plan, usually you’ll take your medication once a day. But it’s important to follow your doctor’s instructions carefully. Based on your specific treatment plan, you might need to take your HIV drugs at a specific time during the day, with food, or even on an empty stomach.

Experts agree that when you take them properly, HIV drugs work very well.

If you skip a dose, take your medication as soon as you remember (unless your doctor says otherwise). But if it’s very close to the time you take your next dose, skip it and continue with your routine. Never take a double dose. It’s very unlikely that you’d develop drug resistance from one missed dose. But still, it’s important to avoid this.

If you continue to miss doses, tell your doctor. People tend to skip doses due to their busy schedules or stressful life events. Explain to your doctor how many doses you missed and why. They’ll be able to help you more if you’re upfront with them.

To stay on top of your routine, consider a few things:

  • Set an alarm or a reminder to take your medications.
  • Keep your HIV medicine in a pill box.
  • Have a loved one or friend remind you to take your medications.

If you find out that you have a drug resistance, the first thing you should do is find out what went wrong. This way, you can make sure it doesn’t happen again.

Luckily, there are other options to treat your HIV. Second-line antiretroviral treatment can help suppress a resistant virus. These usually include integrase inhibitors or boosted protease inhibitors.

Multidrug resistance is uncommon. But if you have this, some medications still might work. Your HIV medication may still suppress your HIV. It just might not work as well. Your doctor may combine medications to help even more.

If you’re resistant to all treatment options, your doctor may see how medications in clinical trials affect you. The good news is experts continue to study many new HIV drugs that are effective against drug-resistant HIV strains.