HIV drugs are designed to keep your viral load under control by preventing the virus from reproducing (or making copies of itself). Sometimes HIV is able to overcome the effects of a drug and keep reproducing anyway. When this happens, we say that HIV has developed resistance to that drug. 

Resistance is a major challenge in HIV therapy. Resistance decreases the ability of HIV drugs to control your virus and knocks out your treatment options. The best way to prevent resistance is to stick closely (adhere) to your HIV drug regimen. With good adherence, resistance is less likely to develop. This will keep more treatment options open to you in the future.  This gives your current drugs the best chance of working and keeps more treatment options open to you in the future.

After infecting a CD4 cell (disease-fighting white blood cell), HIV makes many new copies of itself that infect other CD4 cells. This process happens very quickly – HIV can make billions of new viruses every day. When making new viruses, HIV must copy its genetic information. Copying happens so fast that mistakes are made. These mistakes are called mutations, and they occur randomly.

Some mutations are harmless. They produce weak viruses that can’t infect other CD4 cells. But other mutations cause big problems – they prevent certain HIV drugs from working effectively. If a drug doesn’t work against a mutated virus, the virus will reproduce rapidly. This can cause your viral load to go up, and it may be necessary to change drugs to get HIV back under control.

The main reason to use a combination of HIV drugs instead of just one is to block reproduction as much as possible. A combination of drugs is much better at fighting HIV reproduction than one alone. With less reproduction, mutations and resistance are less likely to occur.

Cross-resistance is another challenge to consider. Cross-resistance happens when certain mutations cause resistance not to just one drug, but to an entire class of drugs. There are five classes of HIV drugs:

• Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) such as Retrovir (zidovudine or AZT) and Ziagen (abacavir)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as Sustiva (efavirenz) and Viramune (nevirapine)
• Protease Inhibitors (PIs) such as Reyataz (atazanavir) and Prezista (darunavir)
• Entry inhibitors such as Selzentry (maraviroc) and Fuzeon (enfuvirtide or T-20)
• Integrase inhibitors such as Isentress (raltegravir)

Cross-resistance is more likely to happen in some classes than others. For example, resistance to the NRTI Retrovir also causes resistance to many of the other NRTIs. Resistance to one NNRTI also leads to resistance to most of the other NNRTIs. This may limit your choices when it is time to pick a new combination of HIV drugs.

If you are starting a treatment regimen for the first time, you should ask your health care provider about alternatives in case the current regimen doesn’t work for you. Thinking ahead like this will help to ensure that you have several good drug choices in the future.

Resistance is common. Between 5 and 20 percent of newly-infected people are infected with strains of the virus that are resistant to at least one HIV medication. This means that some newly-infected people, who have never taken any drugs, already have drug-resistant HIV and have a more limited selection of HIV treatments to choose from. HIV+ people who have already received HIV therapy are even more likely to have resistant virus and fewer drug choices.

The best way to tell if you have drug resistance is to have regular viral load tests. If your HIV drugs are working well to control your virus, your viral load should be “undetectable,” so low that the test cannot detect any virus in your blood. If you are taking HIV drugs and your viral load does not become undetectable or goes up after you have been taking the drugs for awhile, that may mean that your virus has developed drug resistance.

If this happens, you should have a drug resistance test. These tests can help you and your health care provider determine if your virus has become resistant to the medications you are taking and help pick new drugs that will work better.

According to guidelines put out by the US government, resistance testing is recommended for:

• People who have just become infected with HIV, whether or not they are going to take HIV drugs right away
• People who have never taken HIV drugs and are starting to receive medical care, whether or not they are going to take HIV drugs right away
• People who have never been on HIV drugs and are planning to start
• People who are on HIV drugs and see their are viral load go up
• People who have recently started HIV drugs and their viral load is not coming down enough
• HIV+ pregnant women

Resistance testing is not usually recommended for:

• People who have stopped HIV drugs for four weeks or more
• People with a viral load below 500 copies

There are several ways to test for resistance:

• Genotype test
  This test uses HIV from your blood to check for mutations associated with drug resistance
• Phenotype test
  This test challenges your virus with all HIV drugs (in a test tube) to determine which ones are still effective against your HIV
• Virtual phenotype test
  This is a genotype test that goes one step further – it uses phenotype data to predict which drugs will be effective against your virus (and its mutations)

In most cases, the genotype is the preferred test. For people who have been on HIV treatment before and may have HIV that is resistant to a number of different drugs, including protease inhibitors, the phenotype test should be done in addition to the genotype.

Resistance tests are helpful when choosing a drug regimen. The tests are only a guide, however. Other factors, such as past medications, side effects, and adherence must be taken into account as well.

The best way to avoid resistance is to follow your medication regimen closely. Try not to skip doses. Also, try to take your medications at the same time every day. If you follow your health care provider’s instructions, you give the drugs a chance to work as well as possible.

Although resistance may seem overwhelming, remember that you have the power to help prevent it. If you follow your medication schedule, the virus will not reproduce as quickly. And if it’s not reproducing, it can’t make the mistakes that lead to resistance.