One of the greatest challenges of treating human immunodeficiency virus (HIV), is drug resistance. Here’s why: HIV attacks your immune system, specifically your infection-fighting CD4 T cells. The virus replicates extremely rapidly, and during that process it makes a few mistakes, or mutations. Historically, the virus has used these mutations to its advantage, as a way to escape the effects of HIV medication, or antiretroviral therapy (ART). In other words, when HIV mutates, the virus can become resistant to medication -- allowing the virus to continue freely replicating and destroying CD4 cells. If not suppressed by medication, or allowed to freely replicate, HIV will eventually become AIDS, or acquired immunodeficiency syndrome, a condition in which your immune system is so weak, that you are at risk for developing serious, often fatal infections. Thankfully, we’ve come a long way with HIV treatment. Typically, a combination of three antiretroviral drugs is used to suppress the virus. With the combination therapy, the virus is less likely to be able to evade treatment. Today, treatment is so sophisticated that all three drugs are combined into one pill. An Overview of Antiretrovirals HIV medications are divided into six classes, based on how they work to fight the virus: Non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), fusion inhibitors, CCR5 antagonists (CCR5s), and integrase strand transfer inhibitors (INSTIs). Typically, combination ART includes drugs from at least two of these classes. Currently, there are 25 medications currently approved to treat HIV, and numerous combination opportunities available. Choosing a Regimen and Sticking to It Before starting on antiretroviral therapy, it’s important for you and your doctor to consider any other conditions you have, any possible drug interactions between your HIV medication and other medications you’re taking, side effects and the results of drug-resistance testing. Usually, patients are able to start on one of the newer options, which are extremely well-tolerated with fewer side effects, and have convenient one pill a day dosing. Perhaps most importantly, before beginning your regimen, make sure you are ready to take your medication every day as prescribed. Your virus is looking for any opportunity to awake from its dormant state, and if given the slightest chance, it will begin replicating again -- potentially creating mutations that are resistant to your current medication. Once your virus becomes resistant to your regimen, that specific regimen will not be effective again in treating your HIV. Switching Treatments If you experience virologic failure on your first line of treatment, meaning your HIV is still able to replicate to the point where your viral load -- or the amount of viral particles in your blood -- is detectable, then it’s time to switch treatments. A genotype test will determine if a drug-resistant mutation is to blame for treatment failure, and provide information on which antiretrovirals your virus is resistant to. Knowing which antiretrovirals your virus is resistant to will help your doctor determine the best regimen to switch to. Thankfully, there are available options and if drug resistance is caught early, it can be managed. However, it’s important to remember that options are not unlimited. If you fail to take your medication as prescribed and your virus continues to become drug-resistant, you’ll have to take less convenient medications with more severe side effects -- and though rare, we could eventually run out of treatment options for you. The key takeaway? I cannot stress enough the importance of complying with your treatment plan, and communicating with your doctor any potential problems with doing so.