What is Resistance?

Mutations & Resistance in HIV

Managing Resistance to HIV Therapy
Causes of Treatment Failure
- Rational Treatment Sequencing
- Treatment Choices
- Hidden Dangers?
- Resistance Studies
- Measuring Resistance

Resistance Quiz

References

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Managing Resistance to HIV Therapy

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Causes of Treatment Failure
The development of drug resistance is the commonest cause of treatment failure, but there are several other possible reasons for loss of response to anti-HIV drugs¹²:

• outgrowth of resistant strains from residual replication at "sanctuary sites" (such as the brain) not easily reached by anti-HIV drugs
• gastrointestinal intolerance, leading to low drug levels in the blood
• concomitant illness affecting drug availability to the body
• drug side-effects necessitating withdrawal of treatment
• new infection by drug-resistant virus
• failure to keep to treatment schedule
• drug interactions reducing blood levels of anti-HIV drugs

Controlling Viral Replication
Resistance is least likely to develop if treatment is based on a combination of drugs. With this approach, resistance takes longer to develop because a virus strain resistant to one drug could still be sensitive to another. To overcome the action of two or more drugs simultaneously the virus has to acquire multiple mutations. Its chances of getting multiple mutations in the right combination to resist a number of drugs are much smaller than its chance of acquiring a single mutation that enables it to resist just one drug. Specific combinations of multiple mutations are highly unlikely to exist before anti-HIV therapy is started.

Treatment with a combination of three drugs - two nucleoside analogues and a protease inhibitor - is generally regarded as the best way to keep down the viral load¹².