10 Things You Should Know About HIV Drug Resistance

HIV drug resistance is a problem that every person on therapy will eventually face. It can sometimes develop on its own after years of treatment or, more commonly, when a person fails to take the drugs as prescribed. Even more concerning is the fact that the drug resistance can be passed from person to person through sexual contact, shared needles, or other high-risk activities.

Despite the widespread concern about HIV drug resistance, many people remain confused as to why it happens or what they can do to stop it.

Here is a primer that may help:


Antiretroviral Drugs Do Not Cause Resistance

Representation of HIV
James Myhre

When an HIV infection occurs, it is not with a single type of HIV but with a pool of thousands of different variant strains, each a little different from the next.

Drug resistance is caused when the environment of the viral pool is changed. When antiretroviral drugs are added to the mix, the viruses most able to survive take precedence over those that can't. The survivors are what we refer to as resistant viruses.

Over time, the resistant viruses can become the dominant strain. This most often occurs when treatment is either stopped or interrupted, allowing the resistant variants to multiply and eventually predominate.


Wild-Type HIV Is HIV in Its Most Natural State

Wild type HIV
James Myhre

Within the untreated viral pool, the predominant variant is known as wild-type. Wild-type virus is unmuted and can be considered HIV in its most natural state. It is also the most "fit" variant and is able to survive where others can't.

In most cases, wild-type HIV will predominate over all other variants. It is only when the viral pool is exposed to antiretroviral drugs that the make-up of the population will begin to change.


HIV Replicates Quickly but Is Prone to Mistakes

HIV Replicates Quickly
James Myhre

If left untreated, HIV replicates prolifically, producing as many as 10 billion new viruses each day. But, at the same time, HIV is prone to coding errors when replicating. The viruses produced by these mistakes are called "mutations."

"Mutation" does not inherently mean "resistant." The vast majority of these are so distorted they are unable to infect or even survive.

However, on occasion, a mutation will emerge that is able to infect host cells and survive in the presence of antiretroviral drugs. These mutations are drug-resistant.

While they are less "fit" than wild-type viruses, their ability to escape the effects of the HIV treatment give them a better chance of not only surviving but predominating.


Mutations Can Build to Deepen Drug Resistance

Mutations Can Build to Deepen Drug Resistance
James Myhre

Drug resistance doesn't happen all at once. It develops slowly over time as the resistant population continues to replicate and churn out additional mutations.

Every now and then, a new resistant mutation will develop on top of the old one, increasing the fitness of the virus. As more and more of these mutations build, a virus can go from being a partially resistant virus to a fully resistant one.

When the drugs are no longer able to suppress the virus, treatment failure will be declared and a different combination of medications will be needed to restore suppression.


Having a Resistant Virus Doesn't Mean You Are Resistant

Resistant Virus
James Myhre

Resistance is measured in degrees. A resistant variant may be fully resistant, partially resistant, or fully susceptible to a specific HIV drug.

Having a resistant mutation doesn't necessarily mean that your treatment will fail. This is because HIV therapy consists of three drugs, each of which can suppress multiple variants. So, if one of your drugs can't suppress a certain variant, one or both of the remaining drugs usually can.

But, to do so means that you have to take your drugs every day. Having gaps in your treatment only allows resistant variants to replicate and start building additional, potentially harmful mutations.


Resistance Can Be Passed to Other People

Resistance Can Be Passed to Other People
James Myhre

Even if you have been newly infected, It is possible to inherit a resistant virus from the person who infected you. We refer to this a transmitted resistance. There have been cases, in fact, where a newly infected individual has inherited deep, multi-drug resistance to several classes of HIV drug.

According to research from the Centers for Disease Control and Prevention, around one of every six new infections in the U.S. involves a transmitted resistance to one or more antiretrovirals.


Resistance Testing Helps Select the Right Drugs

Resistance Testing Helps Select the Right Drugs
James Myhre

Resistance testing is a type of blood test that helps identify which HIV drugs you are resistant to and which you are susceptible to. It provides your healthcare provider with a snapshot of the types and levels of drug resistance that exist within your viral pool.

By doing so, your healthcare provider can select the combination of drugs best able to treat your unique viral population.


Poor Adherence Gives the Virus a Survival Edge

Poor Adherence Gives the Virus a Survival Edge
James Myhre

HIV therapy is taken daily to ensure that you have enough of the drugs in your system to suppress the virus to undetectable levels. They do not kill the virus but rather prevent it from replicating.

If you don't take your drugs regularly, the levels in the bloodstream will begin to drop and allow the virus to replicate anew. While newer drugs are more "forgiving" and allow for the occasional missed dose, poor adherence still remains the primary cause of treatment failure.

In fact, according to research from John Hopkins University, fewer than 60 percent of Americans on antiretroviral therapy are able to achieve or sustain an undetectable viral load.


Resistance to One Drug Can Affect Multiple Classes

Resistance to One Drug Can Affect Multiple Classes
James Myhre

Because mutations change the physical characteristics (phenotype) of a virus, any resistance a virus may have to one drug will likely affect other drugs of the same class. We refer to this as cross-resistance.

This was a common event with older HIV drugs like Sustiva (efavirenz) and Viramune (nevirapine), both of which belong to the same class of non-nucleoside drug. If you developed resistance, for example, to Viramune (which could happen easily with but a single mutation), you would most likely lose Sustiva as well.

While this is slightly less common with newer antiretroviral drugs, it is still not unusual to experience treatment failure and find that you've lost not only one or two drugs but an entire class of drug.


Resistance Is Not Futile, but It Is Forever

Resistance being passed on
James Myhre

Once you have a resistant virus, you will always have that resistant virus. And, as that virus passed from one person to the next, it can continue to build resistance upon resistance.

As a result, newly infected people may find themselves with fewer treatment options, while re-infected persons may be less able to achieve viral suppression even with complete adherence.

Optimal drug adherence and safer sex practices are key to not only reducing the risk of transmission but extending the lifetime of your HIV drugs.

7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. World Health Organization. HIV Drug Resistance.

  2. UpToDate. Interpretation of HIV Drug Resistance Testing.

  3. Cuevas JM, Geller R, Garijo R, López-aldeguer J, Sanjuán R. Extremely High Mutation Rate of HIV-1 In Vivo. PLoS Biol. 2015;13(9):e1002251. doi:10.1371/journal.pbio.1002251

  4. AIDS Info. HIV Treatment.

  5. National Institute of Health. HIV Treatment.

  6. National Institute of Health. Transmitted Resistance.

  7. Maccarthy S, Hoffmann M, Ferguson L, et al. The HIV care cascade: models, measures and moving forward. J Int AIDS Soc. 2015;18:19395. doi:10.7448/IAS.18.1.19395

Additional Reading

By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.