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.
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.
When a person with HIV does not respond well to a certain medicine, they are said to have drug-resistant HIV. 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 help providers to judge whether a person is resistant to a particular HIV medication, as well as reveal similar medications that might not be right for that person.
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 HIV life cycle. When ART stops HIV from reproducing, the amount of virus in the blood is reduced to undetectable levels. 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 falling.
HIV medications are grouped into seven classes based on how they fight the virus. 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.
When a person’s viral load is undetectable, they are also essentially unable to pass the virus to others through sexual contact. In other words, undetectable equals untransmittable.
A person’s ART medications (or drug regimen) 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.
HIV replicates very rapidly in its life cycle. The virus also tends to develop mutations as it replicates. These mutations are only rarely successful, but those successful mutations may make the virus stronger or better at evading treament. These mutations are passed on to new virus particles during replication.
A form of the virus that has no mutations is called a wild-type virus. ART works most easily on wild-type viruses. 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.
Acquired resistance 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 resistance 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 people experience nausea or vomiting as side effects from ARVs. If a person vomits too soon after taking their treatment, they won’t absorb the proper dose of ARVs into their system.
A person who has a resistant strain of HIV-1 can transmit that drug-resistant variant of HIV to someone else. Someone who is infected by a drug-resistant strain of HIV will not respond to those resistant medications.
Pretreatment resistance is very rare. It can happen in one of two ways. First, when an HIV-negative person is on medicine to prevent becoming infected with the virus, pre-exposure prophylaxis (PrEP), 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.
The second way is when a mother-to-be has HIV and providers 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). 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.
In some cases, a person can develop resistance not just to the ARV medication they’re prescribed, but to one or more other medications in that drug class.
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 at the start of care. This is to establish a baseline from which to assess any HIV resistance. Later on, a provider may suspect a person has drug-resistant HIV because of changes to that person’s blood tests, including a high "viral load."
Drug-resistance testing 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 may discover 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. A health care provider may order additional tests to see why the changes in viral load are happening.
Your doctor may order genotypic testing to determine what gene changes 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. Stanford University keeps a database of the many genetic mutations and the types of drug resistance they cause.
Phenotypic testing 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).
HIV drug resistance limits the number of treatment options 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-choice 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). 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, HIV drug resistance is important to everyone, whether a person is HIV-negative or HIV-positive.
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.
Tell your providers what medicines you take, which symptoms you experience, and if you’re having trouble tolerating or remembering to take your medications. Your doctor can discuss potential solutions to help you adhere to your treatment. For example, some medications 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. Most of the side effects are manageable, but a few can be serious.
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 critical. Take your medicine exactly as prescribed every day. Here are some tips to help you stick to your regimen:
With knowledge and planning, and in partnership with your doctor, you have the ability to lower your risk for developing HIV-1 drug resistance.
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