Options for the highly treatment-experienced

Last reviewed, January 2009

Next review, January 2010

If you have used a lot of HIV drugs in the past, it can be can be more difficult to find a combination of anti-HIV drugs that will work for you. The term ‘salvage therapy’ used to be used for people with very limited treatment options.

But it has now become a lot easier for people who have taken a lot of HIV drugs in the past to find a combination of drugs that is effective. This is because new types of drugs have been approved, and more potent and also because more tolerable and powerful drugs have been developed in the existing classes.

Understanding your options

Until recently, the chance of achieving an undetectable viral load (below 40 or 50 copies/ml depending on the test used in your clinic) if you had taken a lot of HIV drugs in the past was relatively low.

But there have been important new developments that can benefit people with a lot of experience of HIV treatment. Doctors have more experience of looking after people with limited treatment options and new drugs have become available. These advances have increased the possibility of highly treatment-experienced people achieving an undetectable viral load.

First and second line choices of treatment are relatively straightforward in most cases as the range of classes available makes finding a new combinations simple (two nucleoside analogues and a non-nucleoside [NNRTI] can be followed by two nucleoside analogues plus a boosted protease inhibitor).

 For those whose first or second-line treatment has failed, different factors begin to determine which treatments can be used. Some factors, such as drug resistance, low blood concentrations of particular drugs and adherence issues, may influence the approach this time around. When changing your treatments, you and your doctor should consider the reasons previous treatments have failed, before choosing the next regimen.

Resistance testing

Resistance testing is an important tools used in this decision as it can help to identify which drugs are most likely to be effective for you.

Two types of resistance test are available:

• Genotypic tests - these look for specific changes, or mutations, in the virus which may predict resistance to a drug.

• Phenotypic tests – these measure the amount of drug which is needed to control viral replication. As the virus grows more resistant, the amount of drug needed to control replication will increase. This is called loss of sensitivity or susceptibility.

By using resistance testing and treatment history to select a combination that includes as many drugs that will work as possible, an undetectable viral load in people who have used a lot of anti-HIV drugs in the past is now often possible.

New classes

There are three important classes of drugs for people who have taken a lot of HIV treatment in the past.

The first to become available was fushion inhibitors. There is one drug in this class called T-20 (enfuvirtide, Fuzeon).

Maraviroc (Celsentri) belongs to a class of anti-HIV drugs called CCR5 or entry inhibitors. You need to have a special test before starting treatment with this drug to make sure that it will work against your HIV.

Raltegravir (Isentress) belongs to a class of anti-HIV drugs called integrase inhibitors.

Improving current classes

New drugs in the classes already available have or are been designed to work against HIV even if there is a lot of resistance present.

Darunavir (Prezista)/ritonavir and tipranavir (Aptivus)/ritonavir are important protease inhibitors for people with resistance to other protease inhibitors..

Etravirine (Intelence) is an NNRTI that works against HIV that is resistance to other drugs from this class.

Other new HIV drugs are in development, some of which work against HIV in a completely new way.

While the currently available drugs may be enough to manage the virus for some, others will be eagerly awaiting the approval of some of newer treatment options. Where drugs are not currently licensed, they may be accessible through clinical trials, although often certain criteria need to be met. Often, drug companies run expanded access schemes so that patients with few treatment options can obtain early access to the drugs. You will need to be eligible to obtain them, but those with extensive treatment experience are a top priority. Speak to somebody at your HIV clinic for further advice.