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HIV-1 Drug Resistance: What You Need to Know

Posted on March 19, 2020

Article written by
Nyaka Mwanza

  • When a person has drug-resistant HIV, one or more HIV medications or antiretrovirals (ARVs) do not work, or don’t work as well, to bring the virus to undetectable levels.
  • Drug resistance is a problem because it allows HIV to reproduce in the body and become a threat to a person’s immune system.
  • Drug resistance is caused by changes in the virus during replication, called mutations.
  • HIV-1 drug resistance is a manageable issue. People with HIV can reduce their risk of becoming resistant to their medicines.

In 2017, there were nearly 20 million people being treated for HIV. That's almost 50 percent of the global population thought to be living with the virus — an amazing feat since the rollout of antiretroviral treatment (ART) in 2001. What’s worrying is the global rise in HIV drug resistance from 11 percent to 29 percent in the same amount of time.2

It’s important to understand what HIV drug resistance is and why it happens, how to tell if you might have drug-resistant HIV, and how you and your doctors can manage HIV drug resistance. HIV drug resistance can be a problem, but there are many ways to reduce your risk and to manage drug-resistant HIV.

What Is HIV Drug Resistance?

When a person with HIV does not respond well to a certain medicine, they are said to have drug-resistant HIV.1 HIV drug resistance is a term used when a person on antiretroviral (ARV) drugs (also called antiretroviral treatment, or ART) either doesn’t respond to — or no longer responds as well to — a medicine prescribed to treat HIV. ARVs work by stopping the human immunodeficiency virus (HIV) from multiplying or reproducing rapidly in a person’s body. This stops HIV from destroying CD4 cells, the very important immune cells that help protect the body from bacteria and viruses that cause illness.

Drug resistance means that a type of medication doesn’t work very well for a person — and that they likely need a different medication. Testing for resistance, accomplished through genotypic testing, can tell providers if a person is resistant to a particular HIV medication, as well as reveal similar medications that might not be right for that person.14

HIV-1 is a very “smart” virus with a complex way of infecting human cells and reproducing. Antiretroviral therapy to treat HIV has to be just as smart, if not smarter, to treat it. Different medicines stop the virus from replicating by attacking at different stages in the seven-step HIV life cycle.12 Along with stopping HIV from reproducing, ART is designed to reduce the amount of virus in the blood to undetectable levels.11 When a person’s HIV is not treated properly, their viral load is high enough to be detected in lab tests or the number of CD4 cells in their system is low — or both.

Antiretroviral Therapy (ART) for HIV

HIV medications are grouped into seven classes based on how they fight the virus.22 Each class works to interrupt the HIV virus at a specific point in its life cycle. HIV’s life cycle repeats especially rapidly when a person is first infected with HIV.19

The goal of ART is to stop viral replication and make the level of HIV in the system undetectable.21 ART can’t cure the virus,17 but it can reduce the amount of virus in the blood to the point that it:

  • Slows down or stops the virus from replicating in the blood.
  • Reduces the amount of virus in the blood to undetectable levels.
  • Prevents HIV from progressing to AIDS.

When a person’s viral load is undetectable, they are essentially unable to pass the virus to others through sexual contact.22 In other words, undetectable equals untransmittable.18

A person’s ART medications (or drug regimen)9 will usually include three or more medicines from at least two different drug classes. This gives ART more than one chance to stop the virus at different points in its life cycle and increases the chances of a person having an undetectable viral load.

ART works best when a person takes their medications exactly as prescribed by their doctor. That’s why people should consider and discuss many factors when customizing their ART with their providers.1

How Does HIV Become Drug Resistant?

HIV replicates very rapidly in its seven-stage life cycle.16 The virus also mutates often at various points of the life cycle. These mutations are very rarely successful. Successful mutations make the virus stronger or better and are passed on to new virus particles during replication.5

A form of the virus that has no mutations is called a wild-type virus. ART works best on wild-type viruses.5 When HIV medications are prescribed or taken in the wrong combinations, irregularly, or at doses lower than recommended, the mutations that resist ART survive treatment and can be passed on as drug-resistant strains.

When a medication no longer works well to stop the virus from replicating, the virus is said to be resistant to that drug. HIV-1 drug resistance occurs in several ways.1

Acquired Resistance

Acquired resistance1 is the most common way drug resistance develops. The reason people acquire resistance is usually poor medication adherence. This means that they stop taking their medicine or do not take their medicine as prescribed.

Sometimes, a person may acquire resistance to their HIV medicine because of another medicine. Acquired resistance1 can also be the result of poor medication absorption, which can be related to diet. Some medicines need to be taken with food. If they aren’t taken with food, then the body has a harder time absorbing them and a person doesn’t get the full dose. Some drugs have nausea and diarrhea as side effects. If a person vomits or has a bowel movement too soon after taking their treatment, they won’t absorb the proper dose of ARVs into their system.

Transmitted Resistance

A person who has a resistant strain of HIV-1 can transmit that drug-resistant variant27 of HIV to someone else. Someone who is infected by a drug-resistant strain of HIV may find that the type of HIV they have is also resistant to the same drugs.

Pretreatment Resistance

Pretreatment resistance is very rare. It can happen in one of two ways:

  • When an HIV-negative person is on medicine to prevent becoming infected with the virus, pre-exposure prophylaxis (PrEP),1 there’s still a tiny chance they can become infected with HIV. Sometimes when this happens and that person continues taking PreP before they know they have HIV, there’s a small risk that person’s HIV can become resistant to one or both of the drugs used in PrEP.
  • When a mother-to-be has HIV, providers will prescribe medicine to stop the unborn baby from getting the virus. This course of treatment is called prevention of mother-to-child transmission of HIV (PMTCT).1 Like PrEP, there’s a very small chance the mother can pass on the virus to her baby. In the very rare instances this happens, the baby may show resistance to some or all of the drugs used in PMTCT.

Cross-Resistance

In some cases, a person can develop resistance not just to the medication they’re prescribed, but to every medication in that drug class.1

How Does a Person Know If They Have Drug-Resistant HIV?

Drug resistance is usually detected through blood tests. When a person is diagnosed with HIV, the U.S. Department of Health and Human Services (HHS) treatment guidelines recommend resistance testing when referring someone for follow-up care.11 This is to establish a baseline resistance from which to measure HIV resistance. If a provider suspects a person has drug-resistant HIV, it’s usually because of changes to that person’s blood tests. HIV resistance testing is also recommended for women with HIV who become pregnant.

Drug-resistance testing5 helps doctors confirm or rule out drug resistance and helps them determine which ARVs may be more effective. A person’s viral load is the first way a provider knows their medicine isn’t working well. When a new medicine is working well, a person’s viral load should drop to undetectable in the first three to six months of starting it. If a person’s viral load was undetectable but begins increasing, their HIV may have become drug resistant.25 A health care provider may order additional tests to see why the changes in viral load are happening.

Your doctor may order genotypic testing1 to determine what gene changes13 have happened within the HIV-1 virus. For example, scientists have learned that specific mutations may cause the virus to become resistant to certain treatment types.23 Stanford University keeps a database3 of the many genetic mutations and the types of drug resistance they cause.

Phenotypic testing1 is a type of genetic testing that looks at how genetic changes make the virus act differently. For instance, certain classes of HIV treatments stop the virus from replicating at a minimum dosage. If a person’s HIV keeps replicating while they are at or above that dose, they are likely resistant to that specific medicine (or whole class of drugs).

The Impact of Drug-Resistant HIV

HIV drug resistance limits the number of treatment options27 and thus the flexibility one has to manage HIV long term. When the first ART regimen stops working, people with HIV are usually started on a new combination of medicines, also called a second- or third-line treatment. There are fewer options for these second- and third-choice25 treatments once drug resistance has developed.

ART prevents replication and suppresses viral load levels down to undetectable. When HIV is undetectable, it is untransmittable (sometimes expressed as Undetectable = Untransmittable).18 When an HIV-1 drug stops working, the virus is able to replicate again and viral levels can increase. When viral loads increase, the risk of transmitting the virus during sex also goes up. Increased viral load also increases the risk of damage to the immune system and the virus’ chances of progressing to AIDS.

Because treatment and prevention of HIV go hand in hand,18 HIV drug resistance is important to everyone, whether a person is HIV-negative or HIV-positive.

How to Reduce the Risk of Developing HIV Drug Resistance

Drug resistance is manageable; it can also be prevented. Here are important things you can do to reduce the risk of developing a resistance to your HIV treatment regimen.

Talk With Your Doctor

Tell your providers what medicines you take, which symptoms you experience, and if you’re having trouble remembering to take your medications. Your doctor can discuss potential solutions to help you adhere to your treatment. For example, some medications21 are combined into one pill, which can be easier for some people to remember than taking several pills. Your doctor can also help you manage side effects caused by HIV medicines.10 Most of the side effects are manageable, but a few can be serious.

Be Consistent

The most important thing you can do to reduce your risk of developing drug resistance is take your meds exactly as you’re supposed to. That means taking the right medications, the right way, at the right time. Should you take those with food? Could these make you drowsy? Is it time for a refill?

Consistency is king. Take your medicine exactly as prescribed every day. Here are some tips to help you stick to your regimen:

  • Keep track of your different meds with a pillbox or by setting alarms or reminders. You can even download apps to help you stay on track. Some regimens include several different drugs; staying organized and on top of them makes taking them much easier.
  • Make and keep your regularly scheduled health appointments and get your blood work done whenever your doctor recommends. Scheduling appointments with the front desk at the doctor’s office before you leave, signing up for text reminders, and using reminders on your phone or on a wall calendar can help you plan ahead for appointments.

With knowledge and planning, and in partnership with your doctor, you have the ability to lower your risk for developing HIV-1 drug resistance.

Learn more about the human immunodeficiency virus (HIV), its stages and symptoms, and treatment for HIV.

References

  1. AVERT. HIV Drug Resistance. Retrieved from: https://www.avert.org/printpdf/node/2716
  2. Beyrer, C., & Pozniak, A. (2017). HIV Drug Resistance — An Emerging Threat to Epidemic Control. New England Journal of Medicine, 377(17), 1605–1607. doi: 10.1056/nejmp1710608.
  3. Centers for Disease Control. HIV. Retrieved from: https://www.cdc.gov/hiv/default.html
  4. Centers for Disease Control. Living With HIV: Treatment. Retrieved from: https://www.cdc.gov/hiv/basics/livingwithhiv/treatment.html
  5. Clutter, D. S., Jordan, M. R., Bertagnolio, S., & Shafer, R. W. (2016). HIV-1 drug resistance and resistance testing. Infection, Genetics and Evolution, 46, 292–307.
  6. Department of Health and Human Services, AIDS.gov. Antiretroviral Therapy: What Does It Do. Retrieved from: https://aidsinfo.nih.gov/understanding-hiv-aids/infographics/2/antiretroviral-therapy--what-does-it-do-
  7. Department of Health and Human Services, AIDS.gov. Drugs. https://aidsinfo.nih.gov/drugs
  8. Department of Health and Human Services, AIDS.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV: Adherence to ART https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/30/adherence-to-art
  9. Department of Health and Human Services, AIDS.gov. HIV Drug Resistance. Retrieved from: https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/56/drug-resistance
  10. Department of Health and Human Services, AIDS.gov. HIV Treatment — The Basics. Retrieved from: https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/51/hiv-treatment--the-basics
  11. Department of Health and Human Services, AIDS.gov. HIV/AIDS Treatment Guidelines. Retrieved from: https://aidsinfo.nih.gov/guidelines
  12. Department of Health and Human Services, AIDS.gov. The HIV Life Cycle. Retrieved from: https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-hiv-life-cycle
  13. Gibson, K. M., Steiner, M. C., Kassaye, S., Maldarelli, F., & Grossman, Z. (2019). Corrigendum: A 28-Year History of HIV-1 Drug Resistance and Transmission in Washington, DC. Frontiers in Microbiology, 10. doi: 10.3389/fmicb.2019.02590 https://www.frontiersin.org/articles/10.3389/fmicb.2019.02590/full
  14. HIV Drug Resistance. Last Reviewed: February 14, 2016. Retrieved from: https://www.poz.com/basics/hiv-basics/hiv-drug-resistance
  15. HRS Department of Health and Human Services Health Resources and Services Administration; HIV/AIDS Bureau. Guide for HIV/AIDS Clinical Care. (2014). https://hab.hrsa.gov/sites/default/files/hab/clinical-quality-management/2014guide.pdf
  16. National Institutes of Allergy and Infectious Disease. HIV Replication Cycle, Retrieved from: https://www.niaid.nih.gov/diseases-conditions/hiv-replication-cycle
  17. National Institutes of Allergy and Infectious Disease. HIV Treatment, the Viral Reservoir, and HIV DNA. Retrieved from: www.niaid.nih.gov/diseases-conditions/hiv-treatment-viral-reservoir-hiv-dna
  18. National Institutes of Allergy and Infectious Disease. HIV Undetectable=Untransmittable (U=U), or Treatment as Prevention. Retrieved from: https://www.niaid.nih.gov/diseases-conditions/treatment-prevention
  19. National Institutes of Allergy and Infectious Disease. HIV/AIDS. Retrieved from: https://www.niaid.nih.gov/diseases-conditions/hivaids
  20. National Institutes of Allergy and Infectious Disease. The Stages of HIV Infection. https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/46/the-stages-of-hiv-infection
  21. National Institutes of Allergy and Infectious Disease.Starting and Staying on Antiretroviral Treatment. Retrieved from: https://www.niaid.nih.gov/diseases-conditions/starting-antiretroviral-treatment
  22. National Institutes of Allergy and Infectious Disease/National Institutes of Health. Drugs That Fight HIV. Retrieved from: https://aidsinfo.nih.gov/contentfiles/upload/HIV_Pill_Brochure.pdf
  23. Stanford Healthcare. Treatments for HIV/AIDS. https://stanfordhealthcare.org/medical-conditions/sexual-and-reproductive-health/hiv-aids/treatments.html
  24. Stanford Healthcare. HIV Drug Resistance. Retrieved from: https://stanfordhealthcare.org/medical-conditions/sexual-and-reproductive-health/hiv-aids/treatments/hiv-drug-resistance-testing.html
  25. Stanford Healthcare. HIV/AIDS. Retrieved from: https://stanfordhealthcare.org/medical-conditions/sexual-and-reproductive-health/hiv-aids.html
  26. World Health Organisation. HIV Drug Resistance Report 2019 Retrieved from: https://www.who.int/hiv/pub/drugresistance/hivdr-report-2019/en/
  27. World Health Organisation. WHO: HIV drug resistance is present but can be managed. July 18 2012. Retrieved from: https://www.who.int/mediacentre/news/notes/2012/hiv_drug_resistance_20120718/en/
  28. Zazzi, M., Hu, H., & Prosperi, M. (2018). The global burden of HIV-1 drug resistance in the past 20 years. PeerJ, 6, e4848. https://doi.org/10.7717/peerj.4848 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971836

Nyaka has worked with large global health nonprofits focused on improving health outcomes for women and children. Learn more about her here.

A myHIVteam Member said:

My dr had to do the genotype test on me once cuz sometimes i go and im undetectable then i go and im not my dr calls it a blip but my genotype test came… read more

posted 3 months ago

hug (4)

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