HIV Treatment

Drug Resistance

Last Reviewed: July 10, 2026

Key Points

  • HIV can sometimes mutate and become resistant to certain HIV medicines, which is known as drug resistance.
  • Drug resistance can reduce the effectiveness of some HIV medicines, even if they worked well before.
  • Drug resistance testing can identify which HIV medicines will still work and help to choose an effective HIV treatment regimen.
  • Taking HIV medicines exactly as prescribed reduces the risk of drug resistance.

 

What is HIV drug resistance?

As HIV multiplies in the body, it sometimes changes form, known as a mutation. Some HIV mutations can cause resistance to HIV medicines (called HIV drug resistance). With HIV drug resistance, the virus changes and current HIV medicines may not work as well, becoming resistant to all or some parts of an HIV treatment regimen.

In some cases, HIV drug resistance can reduce the effectiveness of multiple drugs in a drug class of HIV medicines. For example, resistance to the nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine can cause resistance to lamivudine or other NRTIs.

Drug resistance can develop over time in people with HIV or can be spread from person to person (called transmitted resistance), which can also occur during pregnancy, labor and delivery, or breastfeeding, through perinatal transmission of HIV. This means that some people can have drug-resistant HIV even before they take HIV medicines.

What does HIV drug resistance do?

HIV drug resistance changes how the virus responds to HIV medicines, which can reduce how well they work and limit treatment options. If HIV medicines stop working effectively, the amount of HIV in the body can increase and it gets harder to stay healthy.

For people who develop HIV drug resistance while taking HIV medicines, the original treatment regimen is unlikely to remain effective. In other words, the original HIV medicines cannot prevent drug-resistant HIV from multiplying, and the HIV treatment will fail unless a different treatment regimen is started.

People with transmitted HIV resistance may not respond to certain treatment regimens, even if they have never taken HIV medicines, including pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP). To prevent HIV from multiplying, it is important to receive drug resistance testing as soon as possible after receiving an HIV diagnosis.

In rare cases, people who have used PrEP or PEP may develop drug resistance. When this occurs, some treatment regimens may not work as well. However, other treatment regimens remain available and can effectively treat HIV. Overall, PrEP and PEP are safe and highly effective tools for preventing HIV.

What is drug-resistance testing?

Drug-resistance testing identifies HIV mutations that can affect how well certain HIV medicines will work. A blood sample is used to check for resistance to common drug classes (such as NRTIs or protease inhibitors).

A health care provider will likely perform drug-resistance testing soon after someone receives an HIV diagnosis so safe HIV treatment can start as soon as possible. Drug-resistance testing helps determine which HIV medicines to include in a person’s first HIV treatment regimen.

Once HIV treatment is started, a viral load test is used to monitor whether the HIV medicines are working effectively. If a person’s HIV treatment regimen is not working, drug-resistance testing is often repeated. The results can show whether drug resistance is the problem and help guide the choice of a new treatment regimen.

How can a person taking HIV medicines reduce the risk of drug resistance?

Taking HIV medicines exactly as prescribed (called medication adherence) helps reduce the risk of drug resistance. Even occasionally skipping HIV medicines can allow HIV to multiply, which increases the risk that the virus will mutate and become resistant to certain medicines.

Before starting HIV treatment, people with HIV should tell their health care provider about any personal concerns that might make it hard to take medicines consistently or preferences for medications taken less frequently. Health care providers can help find a treatment plan that fits a person’s needs and lifestyle, supporting consistent use of HIV medicines.

Taking PrEP exactly as prescribed nearly eliminates the likelihood of HIV transmission, including transmission of drug-resistant HIV. By preventing HIV transmission overall, PrEP lowers the chance of drug-resistant HIV transmission. PEP also reduces the chances of HIV transmission after a possible exposure to HIV. 

The following HIVinfo resources offer more information on drug resistance and medication adherence:

Can people with HIV drug resistance be treated?

People with HIV can still be treated successfully even if the virus is resistant to one or more HIV medicines. Because there are many different classes and combinations of HIV medicines, a treatment regimen can be adjusted to use medicines that will still control the virus.

Usually, at least two HIV medicines from different classes are used together to make treatment work. Some HIV medicines are used specifically for drug-resistant HIV, including the long-acting HIV medicines ibalizumab-uiyk and lenacapavir. See the HIVinfo fact sheets on The HIV Lifecycle and Long-Acting HIV Medicine for more information.

This fact sheet is based on information from the following sources:

From the HIV Clinical Practice Guidelines at Clinicalinfo.HIV.gov:

From the Department of Veterans Affairs:

From the National Institute of Allergy and Infectious Diseases:

Also see the HIV Source collection of HIV links and resources.