What is considered to be a good response to treatment?

It depends on how many drugs you are taking, whether you have taken antiretroviral drugs before, and your viral load before starting treatment. It also depends on when the response is measured.

It is generally agreed that the absolute minimum you should expect to see is 0.5 log (about 66%) after four weeks. Anything less may be a natural variation in virus levels, not a treatment effect.

Treatment guidelines now recommend that in general, failure to suppress viral load to undetectable levels (below 50 copies) after six months of treatment should be regarded as a sign of a poor response to therapy, particularly to a first combination, and should prompt a discussion about whether to change therapy or intensify therapy to try to achieve greater suppression. See Anti-HIV therapy: Changing treatment for further discussion of this topic.

Isn't undetectable load the only acceptable response to treatment?

Most experts would agree that this is the ideal response to treatment because it indicates that viral replication has been reduced to very low levels indeed. People with undetectable viral load after starting drug therapy have the lowest risk of disease progression, and a greater chance that their viral load will stay at very low levels, compared to people with low viral load which is nevertheless detectable.

However, this does not mean that undetectable viral load is the only good outcome of treatment. Some people accept less complete suppression, especially if they have few remaining treatment options. And in any case, for some people it is likely to be impossible to achieve undetectable viral load with the drugs available today.

My viral load has been undetectable for over a year. I am tired of taking the drugs and I am worried about side-effects. What will happen if I take a drug holiday?

It is almost certain that your viral load will rebound above 500 copies/ml within two weeks, according to all the studies of people who have stopped treatment. For most people, viral load will approach or exceed pre-treatment levels within weeks of stopping therapy. Though re-starting treatment should reduce your viral load to undetectable levels again, this cannot be guaranteed.

The different rates at which anti-HIV drugs are processed through the body may cause another problem. For example, 3TC, efavirenz and nevirapine are eliminated from the body much more slowly than most other drugs, and will still be present in your blood at low levels long after other drugs have disappeared. This short period can be enough to allow resistance to emerge, which would prevent you from being able to re-start that drug.

A very small number of people have maintained undetectable or very low viral load after stopping their treatment. However, these seem to be very rare exceptions, and most began treatment very soon after contracting HIV. The reason why these people have been able to maintain suppression of the virus without treatment is not known, and may never be fully understood.

Another important reason why drug holidays are not recommended is because your CD4 cell count may fall rapidly once you stop, putting you at risk of AIDS-related illnesses. It's possible that much of the immune restoration you may have gained from taking treatment will also be lost.

See Anti-HIV therapy: Structured treatment interruption for further discussion of this topic.

My viral load is starting to rise again after nine months below the level of detection. It has gone up to just above 200 copies/ml. Should I change treatment now, or wait?

This may be a sign that your treatment is failing, or it may be a temporary blip caused by an infection. It may even be a laboratory error. It is recommended in these circumstances to have another test as soon as possible to confirm the result. If your viral load is still above the level of detection, that is a signal to consider changing treatment.

People who experience viral load rebound above 50 copies are not necessarily at risk of treatment failure if the next viral load measurement is below 50 copies, or close to that level. It's common for `blips' of this sort to happen. It's when viral load goes above 500 copies that the risk increases. Many people have viral load blips above 50 copies that disappear on the next test or the one after that - the blip may be an incorrect result from the test or due to an infection which is causing a temporary increase in virus production. Just because viral load is undetectable, it doesn't mean that virus production has stopped altogether - it's just going on at a very low level which doesn't do any harm.

See Viral load blips in Anti-HIV therapy: Changing treatment for further details.

Having said that, the level of viral load which you may be prepared to tolerate before switching is likely to be influenced by the drugs you are taking now, your treatment experience and the number of options which are left to you. On a first combination, changing, or intensifying your combination quickly, as soon as viral load has rebounded above 50 copies may be the best way to limit the emergence of resistance, especially if you are taking 3TC, nevirapine or efavirenz. If you have fewer remaining drugs which you have not tried however, you may feel less inclined to act quickly. Several studies have shown that the overwhelming majority of people whose viral load begins to rise again after a period below the limit of detection do not develop any illness over at least a year of follow-up, and continue to enjoy a stable or rising CD4 count.

I've just started therapy on d4T, 3TC and nelfinavir and my first viral load test just came back. I'm not below 50 copies/ml after three months, although it's below 3,000 copies. Should I add more drugs or change them?

There are two views about this question. One argument is that you should do everything possible to get your viral load down as quickly as possible in order to minimise the risk of developing resistance during this period. So if your viral load is still detectable after twelve weeks on treatment, you need to intensify the drug combination, or perhaps change some of the components.

The other view is that a 2 log₁₀ fall in viral load is a very good response at this stage, and that a further reduction may occur over the next three months. If your viral load hasn't fallen further after a few more weeks or months, that is the point to think about what to do next. At that stage you might decide to try new options or you may be content with the fact that the drugs have reduced your viral load to low (albeit not undetectable) levels that are likely to be associated with a much reduced risk of disease progression.