Viral load is the amount of HIV found in a sample of a person's blood. The less HIV found in the blood sample, the less virus one has throughout the body. The less HIV throughout the body, the more slowly HIV disease will progress, if it progresses at all.
Until now, the most sensitive test for measuring viral load (the test which measured the smallest amount of virus per blood sample) has been the old Amplicor HIV RNA test. That test measures accurately down to 400 copies of virus per milliliter (ml.) of blood. However, the new ultrasensitive tests, several of which now exist, all measure viral load down to about 50 viral copies per ml. of blood. Testing undetectable at 50 copies with an ultrasensitive test means that an antiviral combination is keeping viral load as low as available tests can now measure. This is the new goal of antiviral therapy! Studies show that being undetectable at 50 copies on an ultrasensitive test means that antivirals will likely work longer than if viral load is detectable above 50 copies. Of course, this is true as long as the medications are taken on time, and as prescribed, such as with or without food.
Unfortunately, there are still no guarantees even if your viral load is undetectable on an ultrasensitive test. A presentation at this summer's World AIDS Conference showed that those who tested undetectable at 50 copies still had signs of replicating HIV after a year on a protease, AZT/3TC triple regimen. As it is reproducing in the presence of antivirals, such virus could mutate and become resistant to the drugs. Viral load would then increase, or rebound, as the mutant strain of HIV reproduces, unchecked, throughout the body. In fact, there have already been reports of that happening to some people after they reached undetectable on the ultrasensitive viral load test. As a result, doctors are now prescribing combinations even stronger than the standard triple regimens for their patients. It is hoped that these stronger regimens will keep all the HIV inside a person from reproducing and resistance won't develop.
In addition, it is important to remember that you are still infected with the virus when testing undetectable on an ultrasensitive viral load test. HIV has not been completely cleared from the body! In fact, data show that even when the ultrasensitive test is unable to detect virus in a person's blood, significant levels of HIV can still be found in a person's semen or other bodily fluids. This means you can still potentially infect other people with HIV. Therefore, you should continue to practice safe sex no matter how low your viral load is. This includes those who are HIV positive who have HIV infected sex partners. There is now preliminary evidence that someone who is already HIV infected could, in some cases, be co-infected with another person's strain of HIV. This is called superinfection. If this HIV strain is already drug resistant, it might jeopardize that person's antiviral treatment. Until the risks of HIV superinfection are clearly understood, safe sex between positive partners is strongly advised. This will also prevent exposure to other germs that could jeopardize one's health and increase viral load.
The ultrasensitive tests have revealed other limitations of commonly prescribed antiviral regimens. As a result of the new test's increased sensitivity, many on combo therapy who were undetectable using the previous generation of viral load tests, may discover detectable viral load with an ultrasensitive. If the viral load levels are high enough on the new test, at several thousand copies for example, then some resistance has probably already developed to the drugs.
In addition, those whose viral loads test at a very low level on the ultrasensitive test may have reason for concern. In one study, several patients, who were also on a protease, AZT/3TC triple combo, had virus detectable between 50 and 400 copies. This means they would have been undetectable on the older, less sensitive viral load tests. When researchers looked at that detectable virus, they discovered that it was already developing resistance to the triple regimen. Again, some doctors are prescribing stronger drug combinations for their patients. This to insure that viral loads will be brought below 50 copies to prevent, or at least slow down, the development of such resistance virus.
If you are on antivirals and low level detectable virus is found on the ultrasensitive after being undetectable on an older, less sensitive viral load test, don't make an immediate treatment decision based on those results. Confirm the results by repeating the test within two weeks, using the same ultrasensitive test and lab. If low level detectable virus is confirmed, discuss with your physician possible reasons for the increase in viral load. Have you been ill recently, or have you not been taking your antivirals as prescribed? Both could result in an increase in virus. If either wasn't the case then your drug combination was probably not strong enough to keep HIV in check to begin with.
Those who discover they have detectable, low level viral load levels on the new tests, may want to reinforce their regimens by adding other antivirals into the mix. This may prevent further resistance from developing and keep the drugs working longer. Or, a switch to a new, stronger, combination of antivirals may make sense. Both should be done while viral load is still low. At that point, it will also be easier for the new drugs to get viral levels down to undetectable.
For those with detectable virus who may be unable to assemble a new, viable combination of antivirals because they have used up all available drugs, there are new antivirals coming on line or in clinical trials which may offer some benefit. Ask an HIV knowledgeable care provider about such new treatments.
The other alternative for those on therapy with detectable viral load is to sit tight with your current regimen, that is at least according to data presented over the past year by Dr. Steven Deeks of San Francisco General Hospital. Deeks has shown that patients who stayed on antivirals have remained healthy for years after resistance developed and viral load rebounded. That is as long as they have had significant CD4 t-cell increases as a result of therapy. The increased number of CD4 cells, and possibly a weakened form of the virus as a result of the antivirals may be the reason these patients have remained healthy despite drug resistance and viral load rebound.
However, the downside of this approach is the longer you stay on a regimen while viral load is detectable, the more likely cross-resistance will develop. Cross-resistance results when HIV, after developing resistance to one antiviral, becomes resistant to other similar antivirals you have yet to take. So staying on a regimen while viral load is detectable could limit the efficacy of other antivirals you may need later. This is why it is vital to always choose antiviral combinations carefully, keeping in mind how cross-resistance could eliminate the potency of drugs you have never used.
In addition, when you stay on a regimen while viral load is detectable, those viral load levels will continue to rise. This will make it harder for future combinations of antivirals to bring those levels back down. So again, the decision to stay on or switch off antivirals should be made while viral load levels are still low, as well as before cross-resistance has developed to other drugs.
Ultrasensitive tests have already become widely used by laboratories and doctors. In fact, you may have had one done without knowing it. Ask your doctor to see if the viral load test he or she is using is an ultrasensitive test. If your doctor is not using one then you are not getting the best care possible. Make sure your caregiver fixes this situation by getting you access to the new tests.
If you have trouble getting the ultrasensitive test due to lack of health care coverage, a free tests program has been set up by one test manufacturer. Roche Diagnostics is offering free samples of the new Amplicor ultrasensitive test to those who demonstrate financial need. The program provides vouchers for two baseline tests, then three additional tests afterward. For more information, call the Amplicor patient assistance program at 1-888-TEST-PCR. Funding for viral load tests for those with limited means should also be available through most state ADAP programs.
Although the ultrasensitive tests are an improvement over previous, less sensitive viral load tests, they offer no guarantees. HIV is present in the body with transmission of the virus still possible when testing undetectable on an ultrasensitive. Also, viral replication may be ongoing and resistance can develop to antivirals, albeit more slowly, when viral levels are undetectable on the new tests. So the ultrasensitive tests are not perfect tools for monitoring HIV infection and treatment. However, the ultrasensitive tests may not have the final say on measuring viral load; further improvements may be on the way. There are even still more sensitive viral load tests in the experimental stage of development. These "supersensitive" tests can measure down to one copy of virus per ml. of blood. It is hoped that even at such low levels, these "Super" tests will be proven more accurate at measuring viral load and predicting long term health than the ultrasensitive tests. If so, that would mean another new goal for antiviral therapy and even better monitoring of HIV infection. It could be that it's only a matter of time before science advances yet again and the goal of antiviral therapy changes once more.
(The Boston AIDS Writers Group consists of Robert Folan-Johnson; David Scondras, Robert Krebs and Jon Hultgren from Search For a Cure. The Review Panel consists of Dr. Cal Cohen, Research Director of CRI, New England; Paul R. Skolnik, MD, Associate Professor or Medicine, Tufts University; Dr. Robert Kikka, Chiron Diagnostics; Dr. Tony Japour, Abbot Pharmaceuticals; Ken Mayer, Director, Brown University AIDS Project; Dr. Beth Sommers, Research Coordinator, AIDS Care Project; Dr. Greg Flynn. The ideas expressed in this article are those of the Boston AIDS Writers Group and do not necessarily reflect the opinions of the Review Panel.
The AIDS Writers Group is coordinated by Search For a Cure, a non-profit HIV Treatment Education organization. If you have any questions or would like to receive the Reasons For Hope series in its entirety you can contact Search For a Cure at 58 Burbank Street, Boston, MA 02115. They can also be reached by phone at 617-536-2474, by fax at 617-266-0051, or by e-mail at firstname.lastname@example.org.)