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

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Managing Resistance to HIV Therapy

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Treatment Choices
Cross-resistance (viral resistance to more than one drug of the same group) is a risk with all anti-HIV drugs. Varying degrees of cross resistance appear to depend, not only on the type of mutation, but also the number of mutations accumulated. Some researchers have found that the longer an individual with HIV continues to receive an a drug in the presence of rapidly replicating virus, the more mutations accumulate and the greater the degree of cross resistance to other drugs of the same type.

Cross resistance is seen in protease inhibitors to varying degrees dependent on the drug involved. Although a great deal of cross resistance appears to exist between ritonavir and indinavir, the degree of cross resistance between saquinavir and indinavir seems to be less, particularly in people who are switched early after saquinavir failure. Less data are available regarding nelfinavir, but individuals who fail nelfinavir also appear to have developed less cross resistance to indinavir and ritonavir.

A concept (Figure 3) recently presented at the International 37th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) suggests that at the point of drug failure both indinavir and ritonavir resistant virus posses more cross resistant mutations than saquinavir resistant virus. Subsequently, saquinavir resistant virus requires more time to become highly cross resistant.

Figure 3: Evolution of cross-resistance conferring mutations

Although there is little clinical data on individuals switching from one protease inhibitor to another, in the few studies performed to date there does appear to be a relationship between the amount of time individuals received saquinavir after failure to the subsequent efficacy of indinavir therapy (Table 2). Therefore, switching quickly upon initial drug failure is likely to increase the likelihood of a favourable therapeutic response to a subsequent protease inhibitor.

Table 2: PI switching studies (SQV � INV)