YOU ARE HERE:
When to change therapy
The goal of anti-HIV treatment if you are taking it for the first time is to reduce your viral load to below the limit of detection, which is 50 copies in the tests currently used. When your viral load does not fall to this level, it is more likely that your treatment will not suppress HIV for sustained periods of time. A continued rebound in your viral load from very low levels means that your treatment is failing. What may follow is a fall in your CD4 count, a possible risk of HIV-related illness, and an ongoing risk of developing drug resistance. This means that treatment which is not suppressing viral load to below the limit of detection should be changed if there are other drug combinations available to you which are likely to achieve this.
Sometimes your viral load may rise to just above the detectable level and then fall back below on the next test. This is called a 'blip', and means that your viral load should be re-tested as soon as possible, ideally within two weeks. Though one-off blips may be caused by a problem with viral load testing itself, they should also be a trigger to consider other possible causes, such as drug interactions, adherence problems, illnesses or vaccinations. Regular blips may be a sign that your treatment is more likely to fail.
Your treatment is considered to be failing to control HIV only if you have had two viral load tests at least two weeks apart which both show that viral load is above 50 copies/ml. If you have two viral loads above 400 copies/ml a switch of treatment should be considered. It is recommended that a test for drug resistance is done to help choose the replacement treatment, or, if this is not possible (ie if your viral load is below 1,000 copies/ml), that the new treatment involves a completely new set of drugs.
If your treatment is being changed because of side-effects, but your viral load is below 50 copies/ml, it is okay to switch only the drug(s) causing problems.
If you are currently taking d4T and have other treatment options available you are recommended to consider changing d4T because of concerns that it is associated with a high risk of lipodystrophy. AZT has also been associated with lipodystrophy and because of this, if you are currently taking AZT your doctor should discuss the option of switching from this drug to abacavir or tenofovir. Both abacavir and tenofovir also cause side-effects and these should also be explained to you.
If you have had problems with adherence, your failing treatment regimen should ideally be replaced with drugs that are easier to take, and support with adherence should be provided to you. For more information on the steps you can take to improve your adherence see the booklet in this series called Adherence.
Some doctors may consider delaying a switch in treatment if viral load rebounds to a low level, such as between 500 and 1,000 copies/ml. This is because tests for drug resistance (which may help pinpoint which drugs are unlikely to be effective in the new treatment) are more reliable at viral loads above 1,000 copies/ml.
The timing of a switch in therapy will be influenced by the drug options you have available. If a second combination seems very likely to be able to reduce your viral load to undetectable levels and sustain the suppression, then an earlier switch will offer the least possible risk of developing resistance. If you have fewer drug options available, you may be more inclined to switch later.
The causes of treatment failure may be complex. The choice of new drugs should be guided by the availability of new treatment options, your previous treatment history, a resistance test, the chances of getting your viral load below 50 copies/ml, the tolerability of the drugs available to you, and the chances of you adhering to your treatment.
Your new combination of drugs should include three new drugs, including one drug from a completely new class of antiretrovirals, although it is likely to become harder to do this the more anti-HIV drugs you take. Options for people whose first anti-HIV drug combination is failing are shown in Table 3 - see PDF file.
When to change therapy: lipodystrophy
It is now known that anti-HIV therapy can cause changes in body shape and increases in blood fats. The booklet in this series called Lipodystrophy deals with this in detail.
The NRTI d4T has been associated with fat loss, and if you are taking d4T you are recommended to switch it for another drug if you have other treatment options available. In addition, there is evidence of an association between AZT with fat loss and your doctor should discuss the risk of this with you if you are thinking of starting an anti-HIV drug combination including AZT, or are currently taking AZT. You should be offered the opportunity to take abacavir or tenofovir as an alternative. Neither of these drugs have been associated with lipodystrophy, but they can cause other side-effects, and your doctor should explain what these are.
If you have increased blood fats and are taking a protease inhibitor, you may benefit from switching to an NNRTI where this is a viable option. Drugs to control blood fats called statins and fibrates can also be effective and your doctor may recommend them. Changes in diet and an exercise programme may also be helpful. Your risk of developing cardiovascular disease should be assessed taking into account factors such as smoking, your weight, and family history of heart disease.
Changes in treatment appear to have only a very limited effect on body fat changes once they have occurred. These can be very distressing, particularly fat loss from the face. The use of New Fill injections has been shown to help remedy the appearance of fat loss from the face and to improve people's sense of well-being.
Structured treatment interruptions
The value and safety of taking a structured break (called a structured treatment interruption) from your treatment, under close supervision by your doctor, is still under investigation.
Structured treatment interruptions have been studied in people who have recently been infected with HIV, have established (or chronic) HIV infection with a controlled viral load, and people with chronic HIV whose treatment has failed to control viral load.
The main potential benefit of taking a structured treatment interruption is fewer side-effects. However, some people who have taken treatment breaks have experienced complications, including a rapid fall in CD4 cell count and HIV disease progression, and some have developed drug resistant HIV.
Unless you are participating in a clinical trial to assess the benefits and risks of taking a structured treatment interruption, you are only recommended to take a break from treatment if your CD4 cell count was above 400 when you first started taking HAART and has been above approximately 800 for a sustained period.
Changing your therapy after more than one regimen failure: "salvage therapy"
Doctors often make a distinction when talking about people who need to change their HIV drugs for the first time and those who've already made changes before because of the failure of their treatment to control viral load or increase viral load on more than one occasion. The term "salvage therapy" is often used to describe treatment if you have already taken drugs from all the major anti-HIV drug classes.
If your HIV is resistant to a number of anti-HIV drugs, you may find it difficult to assemble a new regimen which can lower your viral load to undetectable levels. The aim of treatment should be to maintain or increase your CD4 cell count and to prevent you from becoming ill.
Structured treatment interruptions are not recommended if you are taking “salvage therapy.”
If you are not at risk of rapidly becoming seriously ill because of HIV (for example you have a CD4 cell count above 100 which is not falling quickly) then you may wish to consider waiting until enough new drugs are available to give you a chance of getting your viral load below 50 copies/ml for a sustained period before you start taking a new combination of drugs. Doctors should not add a single drug which works into your combination to get a short-term reduction in your viral load.