Understanding Lab Tests II: Viral Load, Resistance, and Tropism

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Lab Tests Are Important Tools

Having regular lab tests is a necessary part of caring for your health. If you are living with HIV (HIV+), lab tests are especially important tools that help you and your health care provider keep track of how you are doing in the following areas:

Immune system status

Overall health

HIV illness

  • How HIV is responding to the drugs you are taking
  • Which drugs to use
  • The specific characteristics of your virus
  • Examples of lab tests: viral load test, resistance test, tropism test (explained below)

Viral Load Test

Viral load is the amount (number of copies) of HIV in your bloodstream. Since HIV is a RNA virus, viral load is also called HIV RNA. Viral load can be measured by several different lab tests: a polymerase chain reaction (PCR) test, a branched DNA (bDNA) test, or a nucleic acid sequence-based assay (NASBA). All these tests are accurate, but each has a different way to measure the amount of virus. It is best to stick with the same kind of test and not switch among them or it will be difficult to compare results over time.

Viral load results are reported as copies of HIV in one milliliter of blood. The lower the number, the less virus there is in your blood. Numbers can range from about one million copies to as few as 50 copies. If you have fewer than 50 copies, your health care provider may tell you that your results are "undetectable."

Being undetectable is a great result because it means your virus is under control. However, undetectable does not mean that you have been cured of HIV or that you cannot pass it to others. It just means that there is not enough HIV in your bloodstream for the test to measure. It is also important to know that labs that test viral load have different cut-offs below which they cannot detect HIV. For example: you could have 35 copies of HIV in your blood, and in lab #1, which cannot detect any HIV below 50 copies, your viral load would be considered 'undetectable.' However, in lab #2, which cannot detect any HIV below 20 copies, your viral load would be considered detectable and would report that you have a viral load of 35.

Viral load tests are an important tool to:

  • Check HIV progression
    When compared over time, viral load results show if the amount of HIV in your bloodstream is higher or lower than it was before. The higher your viral load, the greater the chances that your immune system is being damaged.
  • Measure how well HIV drugs are working
    HIV drugs work by preventing the virus from making copies of itself (reproducing). When a combination of HIV drugs (your drug regimen) is working, the viral load usually goes down within weeks of starting the drugs. If your viral load goes up while taking HIV drugs, your drugs may not be working as well as they should.

One goal of HIV treatment is to keep viral load levels as low as possible for as long as possible. This gives you the best chance of staying healthy. With effective HIV treatment regimens, viral load can be reduced to undetectable in many people. This is a great result. It means that your HIV drugs are working and you are doing a great job taking them. However, HIV is still in your body, hiding in an inactive state and not reproducing. If you stop taking your HIV drugs, the virus usually comes out of hiding and starts reproducing; then your viral load will go up.

When Should You Get a Viral Load Test?

  • If you are not on HIV treatment, have a viral load test
    • When you start receiving HIV care
    • Repeat test every three to six months
  • When you start treatment, have a viral load test
    • When starting and two to eight weeks after treatment was started
    • Repeat test every one to two months until viral load becomes undetectable
  • Once you are on a stable treatment regimen and undetectable, have a viral load test
    • Every three to six months
  • When you change treatment, have a viral load test
    • When changing and two to eight weeks after treatment was changed
    • Repeat test every one to two months until viral load becomes undetectable

If your drug regimen is working, your viral load should become undetectable within six months of starting treatment. If this does not happen, if your viral load stays detectable on stable therapy, or if your viral load keeps increasing, it can signal that your drug regimen is not controlling HIV as well as it should. It is important that you and your health care provider discuss all possible reasons (e.g., problems with your body's ability to absorb the drug, problems sticking to your regimen, drug resistance) and take steps to correct the problem. These steps may include additional testing and considering changing HIV drugs.

Resistance Test

HIV drugs are designed to keep your viral load under control by preventing the virus from reproducing (making copies of itself). Sometimes HIV changes, or mutates as it makes copies of itself. These changes may allow the virus to overcome the effects of a drug and keep reproducing. When this happens, we say that HIV has developed resistance to that drug.

Resistance decreases the ability of HIV drugs to control your virus and reduces 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.

Drug resistance tests are used to determine if your virus has developed resistance to HIV drugs. There are several types of resistance tests available.

  • Genotype test
    This test uses HIV from your blood to check for mutations – changes in the virus's genetic sequence or genetic code – associated with drug resistance
  • Phenotype test
    This test exposes your virus to many HIV drugs in a test tube to determine which ones still work against your HIV
  • Virtual phenotype test
    This is a genotype test that goes one step further – it uses phenotype information 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 may be done in addition to the genotype.

When Should You Get a Resistance Test?

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 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 500-1,000 copies

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.

Tropism Test

Tropism describes the way HIV infects CD4 cells. In order to enter a CD4 cell, HIV attaches itself to receptors on the outside (surface) of the cell. Each CD4 cell has a CD4 receptor and two co-receptors called CCR5 and CXCR4 on its surface. To enter the CD4 cell, HIV must attach to the CD4 receptor and either the CCR5 or the CXCR4 co-receptor.

HIV that uses CCR5 to enter the cell is called CCR5 tropic or R5 virus. HIV that uses CXCR4 is called CXCR4 tropic or X4 virus. Virus that uses both co-receptors is called dual or mixed tropic.

Finding out the tropism of HIV is important because there is a class of HIV drugs that work against CCR5 tropic HIV. This class is called CCR5 antagonists or entry inhibitors. CCR5 antagonists work by attaching to the CCR5 co-receptor on the CD4 cell's surface. This blocks HIV from attaching to the CCR5 co-receptor of that CD4 cell. If HIV cannot attach to the CD4 cell, it cannot enter and infect the cell. CCR5 antagonists only work for people whose HIV is CCR5 tropic.

When Should You Get a Tropism Test?

Tropism testing lets your health care provider know if you have CCR5 tropic virus. It is important that you take this test if you are thinking of starting a CCR5 antagonist. At this point, there is only one CCR5 antagonist available called Selzentry (maraviroc), but there are others in development.

Hypersensitivity Test for Ziagen

The HIV drug Ziagen (abacavir) can cause fatal hypersensitivity reactions in some people. Symptoms of hypersensitivity include rash, fever, fatigue, nausea, vomiting, stomach pain, sore throat, cough, and shortness of breath. People with a certain gene (HLA-B*5701) are at risk for developing this hypersensitivity reaction. Consequently, the US Department of Health and Human Services (DHHS) recommends being tested for HLA-B*5701 before beginning treatment with Ziagen.

When Should You Get a Hypersensitivity Test?

If you and your health care provider are thinking about beginning treatment with Ziagen, it is important for you to get the HLA-B*5701 blood test. If you are found to have the HLA-B*5701 gene, the DHHS recommends that you not take Ziagen.

Bottom Line

Regular lab tests are very important in the management of your health and your HIV. Speak to your health care provider about when you need to take the tests described above and how they can be used to help you make treatment decisions.

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