How often should my viral load be measured?

This depends on your state of health and whether you are taking anti-retroviral drugs or not. All guidelines developed so far have recommended that viral load should be tested every three months in people who are not on treatment.

If you are starting treatment it's advisable to get two measurements fairly close together to give an accurate idea of your baseline viral load, and then test again three months after you've started treatment.

Can viral load fluctuate like CD4 cell counts do?

It may. There's still a lot we don't know about viral load, and one of the questions is the extent to which it varies over time if you are not on treatment. For example, we don't really know if the inevitable trend of viral load is upwards, or whether it can remain stable for many months or years. All this information still has to be gathered by research studies.

We do know that some specific factors can cause temporary increases in viral load. These are: vaccinations, a bout of flu, a heavy cold, any other infections. We don't know whether the menstrual cycle affects viral load (it certainly affects the CD4 cell count), and we don't know whether periods of abstinence from alcohol, recreational drugs, anabolic steroids, the oral contraceptive pill or smoking affect viral load in the way that they can affect CD4 cell counts.

My CD4 cell count has fluctuated between 600 and 700 cells/mm³ for the past three years but has suddenly fallen to 500 cells/mm³. My viral load hasn't changed at all. What does this mean?

There could be a number of explanations. One is that you were suffering an infection at the time, but if that were the case one would expect to see a big increase in viral load at the same time. Another possibility is that this is a stress-related change, or that it is a laboratory error. A further possibility is that you have a strain of the virus which is not easily detected by the test kit being used in your clinic. Ask your doctor whether you are being tested with the new Amplicor or Quantiplex assays, which are better adapted to detecting all sub-types of the virus. Also, remember that the typical relationship between viral load and CD4 is seen in the vast majority of people with HIV, but not all. A minority have 'discordant' results, such as a high CD4 cell count and a high viral load, which do not appear to fit with the overall pattern. Finally, have you stopped smoking recently? Smokers' CD4 cell counts can be up to 200 cells/mm³ higher than those of non-smokers.

My CD4 cell count has gone up, but my viral load has gone up too. What does this mean?

Such contradictory changes are not unheard of; biological markers are not infallible. Your viral load could have gone up because you've just had the flu, or perhaps something is artificially inflating your CD4 cell count, such as smoking. It's more important to look at the trend over time, rather than individual changes. CD4 cell counts can rise or fall by hundreds of cells on individual measurements, so it is advisable to have another CD4 cell test and to look at the CD4 cell percentage, which will tell you whether there has been any real rise or fall in the proportion of lymphocytes (white blood cells) which are CD4 T-cells.

If my viral load is undetectable, does this mean that I am no longer infectious?

No it does not. Researchers have investigated changes in viral load in blood, semen and vaginal fluid to see whether they correspond. If the viral load in your blood falls during treatment, it is also likely to fall in your sexual fluids, especially if you have a strong response to antiretroviral therapy. However, viral load in blood and genital fluids does not necessarily match exactly.

For example, it has been shown that infectious virus particles and HIV-infected cells may persist in semen for many months after viral load tests on your blood have ceased to be detectable. It is also likely that infectious virus persists for a long time in the immune cells in the walls of the rectum, even if HIV is undetectable in blood.

It is also possible that even in cases where HIV has become undetectable in semen in response to antiretroviral treatment, low levels of virus will continue to be present. This is because the limits of detection of the viral load tests used so far to study semen have been quite high (over 1,000 copies/ml), and it is very difficult to culture HIV from semen samples if the viral load in a sample is below 10,000 copies/ml. This means that it's impossible to tell whether small quantities of HIV's genetic material found in semen might still represent a high risk for infection.

There are also differences in the ability of viral load tests to detect HIV in semen. The Organon-Teknika NASBA test is more sensitive to HIV in semen than the Roche Amplicor test, because semen contains a chemical which affects the chemicals used in the Roche PCR test, and the Chiron bDNA test appears to be more effective than either NASBA or PCR.

It is unclear how long infectious HIV continues to be present in vaginal fluid after it becomes undetectable in blood. Viral load in vaginal fluid falls dramatically within weeks of commencing antiretroviral treatment, but at present it's unclear whether a large number of latently infected cells persist in the vaginal wall or the cervix for many months after virus becomes undetectable in blood. It's certainly been observed that resistant virus can appear in the blood without developing in cells in the vaginal wall, suggesting that virus in different parts of the body may be affected by drugs in differing ways.

It is known that the amount of HIV in the female genital tract varies over the course of a menstrual cycle, even among women on antiretroviral treatment with undetectable virus in their blood. Current research suggests HIV viral load in the female genital tract gradually rises in the lead up to a womans period and is highest during the period. Viral load in the genital tract then falls to a low point immediately after menstruation. HIV viral load in the cervical canal fluid follows a different pattern. It is highest in the week prior to menstruation when it may be higher than viral load in the blood. In addition, the presence of menstrual blood may mean more virus is present in the genital tract.

It is probably reasonable to assume, based on current research evidence, that it takes a long time for HIV to disappear from semen and vaginal fluid. Even if antiretroviral treatments suppresses viral load in blood to extremely low levels as measured by the most sensitive tests, it may be best to assume that the cells which can release infectious HIV into semen or vaginal fluid will persist in the genital tract and the cervix for many months or even years (See Eradicating HIV? in Anti-HIV therapy: Choosing your treatment strategy for further discussion of the time needed to clear infected cells from the body).

If my CD4 cell count is stable, is there any need to have regular viral load tests?

If you have a high CD4 cell count and you've had one viral load test which is low, you will not be exposing yourself to a big risk if you just monitor your CD4 cell count. This is because your risk of developing AIDS at a high CD4 cell count, even if your viral load shoots up to 100,000 copies/ml in a few months, is still pretty low.

However, if your CD4 cell count is falling fast, or it is below 350 cells/mm³, you will get a great deal of additional information about your risk of developing AIDS by having a viral load test at least once every three months. Whilst your CD4 cell count may be stable at 300 cells/mm³ for a long period, your viral load may begin to change before there is any change in your CD4 cell count. This is an important early warning signal that your risk of developing AIDS is increasing, and that you should consider treatment.

It takes two months for viral load results to come back at my clinic. Is this a reliable guide to what might be happening now?

Only if it indicates that a clear upward trend in viral load is continuing. If you are on treatment, it will not provide a reliable guide to what is happening now. Ideally, you should expect to get viral load results within ten days to two weeks.

My viral load has just doubled from 25,000 to 50,000 copies/ml. My doctor says I shouldn't rush into any treatment decision until I've had another test, but I'm worried that I'm now at higher risk of developing

This change in viral load may not be as alarming as it sounds. In fact, it is within the margin of error of the Amplicor test, and the reality may be that your viral load has been in the range 25,000 to 50,000 copies/ml all along. Your doctor is suggesting that you have another test in order to monitor the trend, and will also encourage you to take into account previous viral load measurements. For example, were they always below 25,000 copies/ml, or have they jumped around? Is your CD4 cell count falling?

As for the risk of developing AIDS, it is worth bearing in mind that the three year risk of developing AIDS with a viral load of 50,000 reaches 40% only when you have a CD4 count below 350. With a CD4 count above 350, the three-year risk of developing AIDS at this viral load level is 16%.

My viral load has gone up from a stable 10,000 to 50,000 copies/ml and my doctor has urged me to consider starting treatment, but I don't want to do so yet. 50,000 doesn't seem that high.

This change in viral load is a fivefold change. Although your risk of developing AIDS is still low at this viral load level, nevertheless the trend is towards a big expansion in virus activity, and you should continue to monitor your viral load carefully. Some clinics would suggest that you have monthly tests for a period in order to assess the trend, particularly if your CD4 cell count is low.