TREATMENT REVIEW 32 - 33 - Fall/Winter 2000

Studies have shown that measuring viral load can help work out a person's risk for disease progression. Studies have also found that measuring viral load can help show if anti-HIV drugs are working. But because viral load tests are relatively new, there are still questions about how the test should be used. There are also important reasons to be careful when making treatment decisions based on viral load test results. This article looks at some of these issues and provides some tips on how to use viral load testing.

Viral Load Variability

One of the most important things to know about viral load tests is that they're not perfect. The test provides a rough estimate of the number of copies of HIV RNA that are in your blood sample. If you take the same blood sample and measure the viral load more than once, you won't get exactly the same result - even though the amount of HIV in the sample hasn't changed. This problem is called variability.

Because of variability, only changes in viral load of more than three-fold can be thought of as important. If your viral load test result changes less than three-fold (for example, from 10,000 to 20,000 which is a two-fold change) it hasn't really changed at all. You should think of a viral load change of less than three-fold as showing that the viral load is stable.

This can be very confusing, because a change from 10,000 to 20,000 sounds like a big increase. The bottom line is that only large changes in viral load should be thought of as important. A viral load that changes from 10,000 to 100,000 almost certainly means that the amount of HIV activity is increasing - this is a ten-fold change.

In addition to the variability of the viral load test, laboratories can occasionally make mistakes. For this reason, anytime there's a big change in viral load it's very important to do a second viral load test to confirm the result. Confirming the viral load test result is even more critical when you're thinking about starting or changing HIV treatments.

HIV Drugs and Viral Load: Undetectable or Bust?

Combinations of anti-HIV drugs ("cocktails," now commonly called HAART, for Highly Active Anti-Retroviral Therapy) can greatly reduce the activity of HIV in the body. Public Health Service (PHS) guidelines on how to use these drugs say that the goal of treatment is to reduce the viral load to "undetectable" levels. An undetectable viral load does not mean that there is no HIV in the body. It means that there are too few copies of HIV RNA in your blood sample for the viral load test to find. As mentioned earlier, the viral load test gives a rough estimate of the amount of HIV RNA in the blood sample - if there is too little HIV RNA, it's like looking for a needle in a haystack and the viral load test can't produce an accurate estimate.

There are different viral load tests available, and an undetectable result can mean different things depending on the test. The first viral load test to become available was the Roche Amplicor PCR test. This test is still widely used. The standard Amplicor PCR test cannot measure fewer than 400 copies of HIV RNA in a blood sample. If you're using the Amplicor PCR test, any result of less than 400 copies will be reported as an undetectable viral load.

There is now a newer version of the Amplicor test available, called the Ultrasensitive PCR. This test can measure down to around 50 copies of HIV RNA in a blood sample. On the ultrasensitive test, a viral load test of less than 50 copies (or 25 copies on some versions) will be reported as undetectable.

Viral Load in Clinical Trials

In clinical trials of HAART combinations, researchers now usually count the number of people whose viral load becomes less than 50 copies (or undetectable) as a result of treatment. This has become a standard way to try and work out how well different HAART combinations work. In recent studies, it has been common for 60-80% of people to have viral loads of less than 50 copies after a year of effective HAART treatment.

Viral Load in the Real World

Doctors report that outside of clinical trials, HAART is usually less successful at reducing viral load to undetectable levels. This may partly be because the intensive monitoring and support used in most clinical trials is not standard practice for a clinic or doctor's office.

One study from an inner city clinic found that only 37% of people had viral loads less than 500 copies after 7-14 months of HAART treatment. Many people struggled with making clinic appointments, taking the drugs regularly (adherence) and drug side effects. Although this sounds like bad news, the same clinic has reported dramatic drops in the number of people progressing to AIDS, getting opportunistic infections or dying.

These real world results suggest that significantly reducing viral load levels can improve health and the function of the immune system, even if the viral load does not become undetectable. The original recommendation that treatment should reduce viral load to undetectable levels was based on a theory that mutations leading to drug resistance would be less likely to occur. However, doctors have now found that low viral load levels don't always mean that drug resistance is developing.

For this reason, many doctors will not necessarily change a HAART combination just because the viral load remains detectable. If the viral load is significantly reduced and there is an ongoing increase in T-cell counts, then treatment may be working well enough to preserve health. Because the number of available anti-HIV drugs is still limited, staying with a HAART combination that seems to be working - even if it hasn't reduced viral load to undetectable levels - may also help save other treatment options for use in the future when they're really needed.

Viral Load and Resistance to Available HIV Drugs

There is another situation where having a detectable viral load despite being on treatment may be okay. A recent study looked at people whose HIV was resistant to most available drugs. The study divided people into two groups. One group continued to take a HAART combination even though their HIV was resistant to the drugs and their viral loads were detectable. The other group stopped HAART to see if the levels of drug-resistant HIV in their body might drop.

In the people that stopped HAART, the levels of drug-resistant HIV did drop. But at the same time, there was a large increase in the amount of HIV in their body that wasn't drug resistant. HAART had been blocking the replication of this virus, kind of backing it into a corner. As a result, only the drug-resistant HIV could replicate while people stayed on their drugs.

When HAART was stopped, the HIV that had been kept under control (what researchers call drug-sensitive or "wild-type" HIV) was able to start replicating. This wild-type virus quickly overtook the drug-resistant HIV in these people. At the same time that the wild-type virus was taking over, their T-cell counts dropped.

The researchers believe that the drug-resistant HIV must be defective in some way, possibly making it less harmful to the immune system. This theory is supported by the people in the study that stayed on HAART. Despite the fact their HIV was drug-resistant, their T-cell counts seemed to stay stable.

For people whose HIV is resistant to available drugs, the study researchers suggest that staying on some kind of HAART combination may still be beneficial. Although the viral load will be detectable and may even be quite high, it looks like keeping the wild-type virus under control may help prevent further damage to the immune system.

Small Viral Load Increases or "Blips"

Another confusing issue when it comes to viral load testing is "blips." This term is used to describe viral load test results that occasionally become detectable at low levels (up to a few hundred copies), but otherwise stays well controlled as a result of HAART. When viral load testing first became available, it was quite common for doctors to worry that these viral load blips meant that HIV was getting resistant to the HAART combination.

Recent studies have found low level viral load blips don't usually mean that the drugs aren't working. Viral load results from two clinical trials of HAART combinations were recently looked at to see how many trial participants experienced blips.

In this study, researchers called a viral load test result of between 50 and 200 copies a blip. Viral loads that increased to over 200 copies but then fell again to less than 50 copies on later tests were also considered blips.

Out of 241 people studied, 97 (40%) experienced occasional viral load blips between 50 and 200 copies. Another 47 (20%) had occasional blips that went over 200 copies.

The researchers then looked to see if these study participants were more likely to experience a more significant increase in their viral load, or what the researchers call a viral load rebound. Viral load rebound was defined as two test results in a row that were over 200 copies.

The researchers found that only 9 out of 96 (roughly 9%) people that experienced blips had a viral load rebound during the study. Out of 145 people in the study who didn't experience any blips (their viral load stayed below 50 copies), 20 (roughly 14%) eventually had a viral load rebound.

These results show that small viral load blips do not increase your risk for developing drug resistance and viral load rebound. Since these studies defined a "blip" as only a few hundred copies of viral load, further research is needed to see if higher blips are associated with viral load rebound.

Illnesses and vaccinations

Temporary increases in viral load have also been reported during acute illnesses (like the flu for example) and after vaccinations. When measuring viral load, it's important to take into account any current or recent illnesses and/or vaccinations that might affect the results.

T-cell Counts and Health

Viral load tests are not a direct measure of your health. The results of viral load tests are used to try and work out your risk of getting sick in the future. A high viral load might mean that you're at a high risk for getting sick next year, while a low viral load can mean you have a very low risk of getting sick over the next few years.

To build a better picture of your health, viral load tests are always used together with T-cell counts. Your T-cell count is a much better guide to how healthy you are today. T-cell counts are also a better guide to your risk of getting an opportunistic infection (OI). Studies have shown that the average T-cell count when someone gets their first OI is 60 cells. It's very rare for someone with over 200 T-cells to get an OI.

Viral Load Tests and HIV Subtypes

Doctors have reported that a viral load test can (rarely) show an undetectable results despite falling T-cell counts and signs of disease progression. One explanation relates to the different strains or subtypes of HIV that are in the world. There are currently many slightly different subtypes of HIV, and the viral load test cannot always detect every subtype. The most common subtype in North America is called subtype B, and the Amplicor PCR viral load test detects this subtype. There are, however, other subtypes that the Amplicor cannot detect. Although these subtypes are more common in other parts of the world, studies have found that they are also present in America. New York City Department of Health (DOH) has a special program that uses viral load tests that look for other less common subtypes. Doctors can contact Bob Garillo at (212) 447-2864 for more information. The DOH can also test for HIV-2, a relative of HIV that is mainly found in West Africa. The African Services Committee of New York also has information on testing for different HIV subtypes, and they can be reached at (212) 683-5021.
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