- Viral Load Test: Overview
- Measuring Viral Load
- "Accuracy" of Viral Load Test
- Viral Load: Interpreting the Results
- Appropriate Use of Viral Load Test
- Viral Load: Availability and Cost
- When Is Viral Load Testing Inappropriate?
Viral load tests allow physicians to track with greater accuracy than ever before the progression of HIV in the body -- thus helping their HIV-infected patients make choices about appropriate treatment strategies. The viral load test is only appropriate for a few specific situations, described below. Most people concerned about HIV do not need viral load testing. The antibody test is still the cheapest, easiest, and overall most reliable way for individuals to learn their HIV status.
There are two kinds of viral load tests. They both measure the amount of HIV RNA in a sample. (RNA is the "blueprint" that HIV uses to make more virus.) When comparing viral load test results to determine a trend, the same type of test must be used each time. It is otherwise like trying to compare the proverbial "apples" with "oranges."
One test, called the branched-chain DNA test (bDNA), is made by a company called Chiron (pronounced "KAI-ron"). The reverse transcriptase polymerase chain reaction or RT-PCR (commonly called the PCR) test is made by Roche (pronounced "RO-sh").
Scientists know how HIV RNA is constructed; it has a distinctive "pattern." By creating a mirror image of that structure and matching it against what they find in a blood sample, they can measure HIV RNA.
The RT-PCR test chemically multiplies viral RNA that exists in the sample by a factor of approximately one million (this is the "chain reaction" which its name describes). The amount of RNA in the sample is then easy to measure, but that amount is calculated, so this test measures the RNA indirectly. More about why that's important below.
The bDNA test sets off a chemical reaction with HIV RNA so it emits (gives out) light. More light means there is more RNA. The amount of light measured indicates the level of RNA in the sample. This test measures RNA directly.
Why is indirect or direct measurement important? Because the same sample, tested with both tests, will give different viral load measurements. Here's another way to think of the differences between these two tests: One way to describe weather is to state the temperature. A thermometer is a common gauge for measuring temperature. It can measure temperature in degrees Celsius or in degrees Fahrenheit. Both measurements are "accurate," but they describe the same weather differently (when it is 25 degrees Celsius, it is 72 degrees Fahrenheit).
The same is true for HIV viral load testing. Both bDNA and RT-PCR tests measure the amount (or "load") of HIV in the blood. The test methods ("thermometers") are different, but what they are measuring (the "weather") is the same.
Viral load varies, sometimes a lot, over time. One viral load test, interpreted by itself, is not meaningful. It must be looked at with other tests, such as T-cell (CD4) count, or compared to other viral load tests to be helpful as an indicator of HIV progression.
The results of viral load tests are usually given as "copies per milliliter (ml)" of blood, like the CD4 (T-cell) count. Each virus carries two copies of RNA. If there are 100,000 copies of HIV RNA, that means 50,000 virus particles (or virions) are present. Currently:
The RT-PCR test (second generation) can identify as few as 40 copies of HIV RNA.
The bDNA test (second generation) can identify as few as 50 copies of HIV RNA.
Test results can be variable (different), even when repeated on the same blood sample. Any test report should also indicate the variability of the test. For example, the result may be 20,000 copies with a variability of 5,000. The viral load is then somewhere between 15,000 and 25,000 copies.
There is a lot of HIV in other places in the body, not just the blood. Only a fraction of HIV is in circulating blood; the rest is in the lymph system and other body tissues. Other factors may influence the variability of a test; viral infections, such as a cold or the flu, can cause a temporary increase in viral load. For this and other reasons, physicians usually request two or more tests over a short period of time (within two to four weeks) to establish baseline viral load.
As with the ELISA HIV antibody test and other medical tests, "accuracy" is a combination of sensitivity and specificity. Sensitivity of a test is its ability to detect the virus when it is present, and to not report "false negative." Specificity of a test is its ability to detect only HIV and nothing else, so as not to report false positive. Ideally, a test is both very sensitive and very specific. In practice, increasing sensitivity decreases the specificity, and vice versa.
Viral load testing is extraordinarily sensitive, but it is not perfect. The most sensitive viral tests can only detect 40 or more viral particles per milliliter in a sample. It is therefore false to assume that an "undetectable viral load" means there is "no HIV present." A person with "undetectable viral load" can indeed transmit the virus to someone else.
The downside to PCR's sensitivity is its somewhat lower ability to eliminate false positive results caused by RNA other than HIV. This incredible sensitivity also means that the smallest inattention while cleaning lab equipment after a previous infected sample could contaminate a negative sample and cause a false positive.
Physicians presently use baseline viral load to help their HIV-infected patients make choices about appropriate treatment strategies. Patients and their doctors can assess the need to adjust treatment based on their ongoing observations and monitoring of changing viral load levels over time. Because viral load testing is still a relatively new diagnostic tool, baseline viral load is used as one indicator of viral activity, but is not yet determined to be an absolute. Generally, most practitioners consider "low" baseline viral load to be approximately 500 or fewer copies of HIV RNA, and "high" to be any number above 40,000 copies. It is further believed that viral load may be a good marker or predictor of disease progression.
There is a correlation between CD4 level and viral load. Most people with higher CD4 cell counts have lower viral loads; conversely, people with higher viral load tend to have lower CD4 cell counts. (CD4 level is one indicator of how well the immune system is functioning.) Monitoring both CD4 level and viral load provides a more complete picture of immune health than using either test alone.
The viral load test is only appropriate for a few specific situations. Most people concerned about HIV do not need viral load testing. The antibody test is still the cheapest, easiest, and overall most reliable way for individuals to learn their HIV status.
Viral load testing is appropriate in the following circumstances:
You are already diagnosed with HIV/AIDS.
The viral load test is one of several great tools for doctors to assess the efficiency and health of a person's immune system. Ongoing viral load monitoring can inform the physician that it may be time to consider beginning or changing antiviral therapies.
Infants born to HIV-positive mothers.
These infants will always test positive on the antibody test during the first 12 to 18 months of life because they carry their mother's antibodies, not their own. Because a 12 to 18 month delay in making decisions about an infant's health care may be unacceptably long, viral load testing can be used six months after birth to determine whether the child is infected. Even in this instance, antibody tests will always be done at a later date to confirm a positive PCR.
Pregnant women who may have had a recent exposure to HIV.
Obviously, a pregnant woman trying to decide whether to continue or terminate her pregnancy cannot wait three to six months for the results of an antibody test. Viral load testing can enable pregnant women at risk to make more informed decisions, including whether to start prenatal antiviral therapy which will significantly reduce mother-to-child transmission. The woman and her doctor may consciously decide that the benefit of preventive treatment during pregnancy outweighs the risk of obtaining false positive PCR results.
Individuals recently involved in a very high risk exposure (within the last 72 hours or less) who have access to post-exposure prevention treatment.
PEP, as it is also referred to, is a theory of early treatment whereby individuals at recent high risk are immediately given a 30-day regimen of several antiviral drugs. This is currently available, to our knowledge, only through an experimental research program in San Francisco, or through a few individual doctors elsewhere. This treatment is not proven effective and is only in its exploratory stages.
Note: In each case but the first, the person will likely undergo a qualitative PCR test, which is related to a RT-PCR. The qualitative PCR does not measure the amount of HIV RNA, it detects the mere presence of HIV. It is so sensitive that it can detect one virus particle in a sample of 100,000 cells.
So, if it is so sensitive, why isn't PCR used for HIV diagnosis for everyone? Read the section on inappropriate use of viral load testing below.
Any physician can order a viral load test. Contact your own physician, or a community clinic.
The test can cost around $150 if you have to pay for it out-of-pocket. However, HIV-positive people (or others with valid reasons for needing the test, discussed above) who have Medi-Cal (in California) may be able to get it free through their local public health department or county hospital. Various research projects may offer free PCR testing if an individual is part of that specific study.
The vast majority of people concerned about HIV infection do not need viral load testing. In nearly all cases, this is not a test we recommend for assessing one's HIV status.
Why shouldn't someone use a PCR test to get quicker HIV test results?
Answer: Because the test was not designed for that purpose, it could easily report either false positive or false negative, it is much more expensive than antibody testing (and not covered by insurance for this purpose), it is confidential, rather than anonymous testing, and any PCR result must be followed by an antibody test after the appropriate interval in order to be meaningful.
Can someone get a PCR test to diagnose HIV faster than antibody screening?
Answer: Yes, if they are willing to pay for it. But:
Does it give them a true report of their HIV status?
Answer: NO! They will still need an antibody test later, after waiting through the window period.
In many cases, people who want PCR testing to determine their HIV status are highly concerned/anxious. They are unwilling to wait through a three to six month window period and take an antibody test. They may have heard that PCR testing will indicate HIV status sooner than antibody testing. In some clinical research settings, this is true. Why only in research settings?
Because PCR testing is so sensitive, labs must be scrupulously careful to avoid errors caused by previous samples. Even with the most diligent lab procedures, there is a very real possibility of a false positive PCR.
On the other side of the scale, it is well known that there are many HIV-positive people who have "undetectable" viral load thanks to protease inhibitors. So false negative results are also quite possible if PCR is relied upon to make a diagnosis for HIV.
In research settings, other "controls," such as multiple tests and studying only those people who are confirmed to have been at high risk, reduce (but do not eliminate) the chance of making an error. However, HIV antibody testing, performed after the window period, is still required to confirm PCR test results, even in those highly controlled research environments.
Other reasons to not recommend viral load/PCR testing for HIV diagnosis:
Some businesses prey on the fear and impatience of anxious individuals. They know that concerned people will pay steep fees to have PCR testing performed for purposes other than those for which it is intended (i.e., HIV diagnosis).
Because PCR tests must be ordered by a doctor, they are by definition confidential, rather than anonymous. Positive PCR results (remember false positive is certainly possible) could become part of medical records, which are then available to insurance companies. And remember that even the fact that someone took an HIV specific medical test, regardless of the results, could be a factor in denying future insurance coverage.