HIV Drug Resistance (HIVDR) is caused by a change in the genetic structure of HIV that affects the ability of drugs to block the replication of the virus. This change results in a mutation. People with HIV may have one or several drug-resistant mutations, making HIVDR a major factor in the failure of HIV treatment, also called antiretroviral therapy (ART). When HIV medicines do not work like they should, this negatively affects public health.

Millions of people around the world take antiretroviral (ARV) drugs to treat HIV infections. About 26% of people starting treatment are infected with a virus carrying resistance to first-line ARV drugs. Up to 69% of infants born to mothers infected with HIV have pretreatment HIVDR.

How do you develop resistance to HIV drugs?

There are 3 types of HIV Drug Resistance:

  • Acquired HIVDR occurs when virus can mutate and reproduce while a person is on ART. This can happen when you do not stick to your HIV treatment plan or when you are taking other medications that make your ARV drugs less effective. All current ARV drugs including newer class can potentially become fully or partly ineffective.
  • Transmitted HIVDR happens when a drug-resistant HIV strain spreads from person to person. People with transmitted resistance have drug resistance even before they start taking HIV medicines.
  • Pretreatment HIV drug resistance applies to resistance detected in people starting ART with or without taking ARVs drugs. People can have this at the time of infection or acquire during previous treatments.

How to know if you have or have developed drug resistance?

When you start ART, the prescriber may do a drug resistance test so you may know if you have drug resistance.

The goal of HIV treatment is to reduce a person’s viral load to an undetectable level. You may develop drug resistance if you have been taking your HIV medications properly, but your viral load does not become undetectable or goes up. It is important that you get a drug resistance test.

What is HIV drug resistance testing?

Drug-resistance testing is used to identify if your HIV strain is resistant to one or more drugs. This can help to determine which drug will and will not work against your HIV infection.

There are 2 types of testing assays used to assess viral strains:

  • Genotypic testing looks for any genetic mutations of HIV that are known to cause resistance. This is a preferred method for people having problems with their first- or second-line treatment.
  • Phenotypic testing measures the sensitivity of a patient’s HIV in response to specific ARVs. This is a preferred method for people with known or suspected resistance in addition to genotypic assay.

What can you do to prevent HIV drug resistance?

If you have HIV and start ART, tell your doctor about any issues that make it difficult for you to take your medication consistently. This is important to create a personal treatment plan that will work for you.

If you are taking ART, you should take your medications as directed by your doctor. When taking properly, HIV drugs work very well and can help you avoid drug resistance. It is also important to follow up with your doctor routinely to monitor your treatment progress.

If you have trouble remembering to take your medication, discuss with your doctor or you can consider these few tips:

  • Set an alarm or reminder to take your medications.
  • Put a reminder note where you can see it every day.
  • Keep your HIV medicines in a pill box.
  • Use pill box that has alarm with automatic pill dispenser.
  • Have your family members or friends remind you to take your medications.

What to do if you develop resistance to HIV drugs?

If you find out you have drug resistance, your doctor will work with you to decide other treatment options that work for you. However, you should discuss with your doctor to see what went wrong to make sure it does not happen again.

Recent advancements in HIV drug resistance treatment:

  • Lenacapavir is a first in class long-acting HIV medications for treatment of multi-drug resistant HIV infection,
  • Symtuza is complete treatment for HIV infection that reduces the risk of drug resistance.
  • Biktarvy got new FDA approval for new indication in 2024 to treat HIV in patients who have suppressed viral loads with known or suspected M184V/I resistance.

References

Melku M, Gesesew HA, Ward PR. Magnitude and predictors of HIV-Drug resistance in Africa: A protocol for systematic review and meta-analysis. PLoS One. 2022 Apr 20;17(4):e0267159. doi: 10.1371/journal.pone.0267159. PMID: 35442975; PMCID: PMC9020684.

Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. NIH. Published Mar 23, 2023. Accessed Mar 21, 2024. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/drug-resistance-testing

Drug Resistance. NIH. Published Aug 4, 2021. Access Mar 21, 2024. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/drug-resistance

 FDA Approves Sunlenca. Published Dec 2022. Accessed Mar 21, 2024. https://www.drugs.com/newdrugs/fda-approves-sunlenca-lenacapavir-twice-yearly-living-multi-resistant-hiv-5946.html

FDA Approves Symtuza. Published Jul 2018. Accessed Mar 21, 2024. https://www.drugs.com/newdrugs/fda-approves-symtuza-d-c-f-taf-first-only-complete-darunavir-based-single-tablet-regimen-hiv-1-4782.html

U.S. FDA Approves Expanded Indication for Gilead’s Biktarvy to Treat People with HIV with Suppressed Viral Loads, Pre-Existing Resistance. Published Feb 2024. Accessed Mar 21, 2024. https://www.drugs.com/newdrugs/u-s-fda-approves-expanded-indication-gilead-s-biktarvy-hiv-suppressed-viral-loads-pre-existing-6200.html