Choosing the next regimen

When changing antiretroviral therapy, it is important to switch to drugs that are active against a person's virus. An individual’s treatment history and resistance testing can help determine which drugs are likely to be effective when changing regimens due to virological failure.

In some cases, resistance to one drug may confer cross-resistance to similar drugs in the same class. Besides the number of resistance mutations, other factors that predict success with a subsequent regimen include low viral load and number of active drugs in the combination.

When switching due to virological failure, it is best to change all drugs, if possible. If HIV is resistant to all drugs in the current regimen, changing just one has the same effect as monotherapy. When considering a switch to a newly available drug, for example an entry inhibitor or integrase inhibitor, it is essential to optimise the background regimen, using resistance testing to ensure that the combination contains as many drugs as possible with activity against the virus.

The development of novel drug classes provides additional options for people experiencing treatment failure. The fusion inhibitor T-20 (enfuvirtide, Fuzeon), the CCR5 antagonist maraviroc (Celsentri) and the integrase inhibitor raltegravir (Isentress) are approved and available. The advent of T-20 has allowed many highly treatment-experienced patients to achieve an undetectable viral load, and the other novel drugs are likely to do the same. However, all these drugs will work better – and for longer – if combined with other agents that are still active against HIV.

Drug cycling, or alternating between two or more different drug combinations, has been suggested as a strategy that could potentially slow the emergence of resistance or overcome existing resistance by allowing wild-type HIV to periodically re-emerge. Drug ‘recycling’ refers to reusing older drugs that have been taken in the past, in the hope that the virus will have regained susceptibility. With the advent of novel drugs, however, this approach has fallen out of favour.

Several studies have shown that treatment that only partially suppresses HIV can still provide benefits in terms of maintaining immune function and delaying clinical disease progression. Further, staying on inactive drugs may encourage the persistence of less fit drug-resistant mutant virus strains. If a person has a viral load that is not too high, a CD4 cell count that is not too low, and few or no remaining active drugs available, continuing on a ‘failing’ regimen may be an option.

However, this must be weighed against the risk of further resistance emerging if HIV is allowed to replicate – even at a low level – in the presence of a drug. With today’s improved therapies, the goal is to push viral load below 50 copies/ml, which is often possible even for highly treatment-experienced people with extensive drug resistance. There is an array of expanded treatment options with two non-peptide protease inhibitors, a new non-nucleoside reverse transcriptase inhibitor, and three entry inhibitor drugs offering the best chance in years to put together subsequent regimens containing two or more drugs active against highly resistant virus.

Given all the right tools – including new drugs, resistance testing, and good adherence – treatment-experienced people on subsequent regimens have a good chance of surviving as long as those who are just starting antiretroviral therapy.

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.