HIV drugs are designed to keep your viral load under control by preventing the virus from reproducing (or making copies of itself). However, 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 control over HIV 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.

After infecting a CD4 cell, HIV reproduces itself. It makes many new viruses that infect other cells. This process happens very quickly – HIV can make up to 10 billion new viruses every day! During reproduction, 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 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 the viral load to go up, and it may be necessary to change drugs to get HIV back under control.

One of the reasons to use strong combination therapy for HIV is to block reproduction as much as possible. With less reproduction, mutations and resistance are less likely to occur.

Resistance to certain classes of HIV drugs can develop more easily than resistance to other classes. For example, HIV only needs one particular mutation to become resistant to all the NNRTIs (drugs like Sustiva [efavirenz] and Viramune [nevirapine]). Resistance to other classes, like the protease inhibitors (PIs), is more difficult to develop. Two or more mutations are required before resistance to PIs occurs.

Resistance is very common. Studies have shown that 12 percent of people who are newly infected with HIV get a strain that is already resistant to one drug (most people are still infected with “wild-type” virus or virus that is not resistant to any drugs). Six percent of patients get a strain resistant to two or more drugs. This means that newly-infected people, who have never taken any drugs, may already have a limited selection of HIV treatments due to resistance.

HIV+ people who have already received HIV therapy are even more likely to have resistant virus. One study showed that 78 percent of patients who have been treated were resistant to one drug. Fifty-one percent of patients were resistant to two or more drugs.

Cross-resistance is another challenge to consider. Some mutations cause resistance not to just one drug, but to an entire class of drugs. For example, certain mutations causing AZT resistance also cause resistance to most of the other NRTIs. In addition, resistance to one NNRTI leads to resistance to all currently available NNRTIs. This may limit treatment options when it is time to pick a new regimen.

If you are starting a treatment regimen for the first time, you should ask your doctor about sequencing. Sequencing is like a “game plan” for HIV therapy. Your doctor should not only choose what you will start with, but what drugs you can switch to if your first regimen stops working. In other words, you and your doctor should be thinking about your second and third possible regimens while planning your first HIV drug combination. This should leave several good drug options open for the years ahead.

There are several ways to test for resistance:

• Genotype test
  This test uses HIV from your blood to check the genetic sequence of the virus 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 from many patients to predict which drugs will be effective against your virus (and its mutations)

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

Resistance tests can be useful in the following situations:

• Someone who was just infected with HIV (acute infection)
  Testing is used to see if the patient was infected with a drug-resistant strain
• Someone who is failing his or her current regimen
  Testing is used to guide the choice of a new regimen
• A pregnant woman
  Testing is used to determine the best regimen to prevent mother-to-child HIV transmission

The best way to avoid resistance is to follow your medication regimen closely. Try not to skip doses. Also, try to take your meds at the same time every day. If you follow your doctor’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. This will keep treatment options open for the future!

1		Hirsch, M.S., et. al. (2000). Antiretroviral drug resistance testing in adult HIV-1 infection: Recommendations of an international AIDS society-USA panel. Journal of the American Medical Association 283(18). 2417-2426.
2		Shafer, R. (2002). Assays for antiretroviral resistance. HIV InSite Knowledge Base Chapter. Retrieved July 2003 from http://hivinsite.ucsf.edu/InSite?page=kb-02-02-03.
3		United States Department of Health and Human Service’s AIDSInfo. (2004). Guidelines for the use of antiretroviral agents in HIV-infected adults and Adolescents: Retrieved July 2003 from http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50.