AIDS TREATMENT UPDATE, Issue 42, June 1996
Edward King

Viral load tests act as a marker of the number of HIV particles in a sample of blood by detecting the virus' genetic material, RNA. During the last year, several studies have suggested that:

- among people who have not taken anti-HIV drugs, viral load may be the best predicator of their time to developing AIDS or dying

- among people who are starting anti-HIV treatment, the change in their viral load after the first few weeks may predict the longer-term effects of the drug(s) on disease progression and survival

On the basis of these findings, many clinicians in the USA and parts of Europe such as France have started to use viral load measurements routinely to help inform treatment choices. For more information, see AIDS Treatment Update issue 39.

However, there are still many unanswered questions about the meaning of viral load test results. While more and more British clinics are likely to offer the tests to some or all of their patients over the coming months, there remain doubts over what a individual's test result actually means, or what treatment decisions he or she should make in response.

Most clinicians, including Professor Pinching, now believe that knowing your viral load may provide an extra piece of information to help you decide whether and when to start taking anti-HIV treatments. However, Professor Pinching wonders "once you have hit the virus with anti-virals, do we still understand how to interpret viral load measurements?"

People who take anti-HIV drugs commonly see their viral load fall in response to therapy, but in many cases it eventually returns towards its starting baseline value or higher. Professor Pinching argues that it is unclear what these changes reveal about whether or not an individual is still benefiting from a drug. "I'm concerned that viral load results are likely to encourage us to make premature decisions. With AZT, for example, the viral load typically returns to baseline after only six to eight weeks, yet the clinical benefit we see in patients lasts on average about two years. If we used viral load changes to decide when a drug was no longer working, we would encourage patients to go hopping quickly from drug to drug when that may be inappropriate given the limited repertoire of drugs that we have."

Speaking at the Treatment Action Taskforce's monthly information forum in London in May, Dr Margaret Johnson of the Royal Free Hospital was broadly in agreement. "With viral load changes in response to treatment, we don't know whether the important element is the size of the initial decline, the actual level to which it drops, how long the viral load stays suppressed, or a combination of all of these factors". There are also uncertainties about whether changes in viral load in the blood are representative of changes throughout the body (for example in the lymph nodes), and the relative usefulness of changes in viral load versus changes in CD4 count over time.

Advocates of viral load counter that by keeping viral load as low as possible for as long as possible by adding or changing treatments when the viral load returns towards baseline, the duration of clinical benefit might be extended. Professor Pinching agrees that while this may be the case it has still to be proven, and the number of drugs to change to is limited. For now it is important to remember that viral load tests remain experimental.

Professor Jonathan Weber of St Mary's Hospital supports the use of viral load tests in routine clinical practice, and favours using a second virological test to assess whether people taking anti-HIV drugs have developed resistant HIV strains. "It doesn't make sense to think about viral load in isolation from resistance. The emergence of resistance is one reason why viral load levels may return after therapy, and the decision whether to add new drugs or switch to an entirely new regimen will probably depend on whether the patient is still sensitive to the original therapy. I believe we're going to have to offer resistance testing as an NHS service at Mary's this year, as it's the only way to find out when to stop a drug."

PSYCHOLOGICAL ISSUES

People who are thinking of having their viral load measured also need to consider the potential impact of the result. Michelle Holder, a research nurse at the Kobler Centre in London, says that the psychological effects of having a viral load test are similar to those of the HIV antibody test, and need to be considered just as carefully.

Many people who have viral load tests as part of the clinical trials offered at the Kobler Centre have been unprepared for the trauma of discovering that the result is high. Michelle Holder recommends that people think carefully and spend some time with a doctor, nurse or other advisers preparing themselves for the possibility of a high result.

Such counselling also needs to highlight the factors that can cause artificially high viral load. For example, people whose immune systems are activated - perhaps from an active infection such as herpes - may have a temporarily high viral load that will return to a lower level after the immune stimulation is removed. Like CD4 counts, other day-to-day factors may cause the viral load to fluctuate, so some doctors argue that a viral load result should be confirmed with a second test if it is to be used as the basis for important decisions such as treatment choices. However, some clinics say they will not be using repeat tests, as it significantly increases the cost implications of offering viral load testing. Researchers suggest that it will be more useful to monitor trends in viral load over time, rather then to make decisions based on individual measurements.

At present, viral load testing is not routinely available at clinics in Britain. As it becomes more accessible during the coming months, these psychological considerations mean that people should think carefully about when - or whether - to have their viral load measured.

MAKING A PLAN

One strategy to address both the medical uncertainties and the psychological consequences of viral load testing is to discuss the possible outcomes and decide on your potential courses of action with your doctor before your viral load is measured.

For example, a person who has a gradually declining CD4 count of around 300 but no symptoms, and who is uncertain whether or not to start taking anti-HIV drugs, may decide in advance that a high viral load test result would tip the balance in favour of starting treatment, but a low result would lead him or her to delay treatment for the time being.

Similarly, a person who has been taking an anti-HIV regimen for many months might decide in advance to add or change drugs if a test shows that his/her viral load has risen significantly compared with an earlier measurement. Before having the test, it is worth considering precisely which additional drugs would be available.

On the other hand, after considering the options carefully and taking account of the uncertainties about viral load, someone who is taking anti-HIV drugs and has a relatively stable CD4 count and no symptoms may decide that he would not want to change his current treatment even if a viral load test result was relatively high. In that case, there may be little point in having the test at all.

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