HIV Drug Resistance and Insufficient Drug Plasma Levels as Factors Determining Antiretroviral Treatment Failure

The present aim of antiretroviral therapy is to suppress HIV replication as much and as long as possible in order to avoid development of AIDS. Although an increasing number of drugs is available to treat HIV-infected patients, virological treatment failure is still frequent in everyday clinical practice. Many factors have been recognized to explain this failure and are related to the virus, the host or the drugs themselves. HIV drug resistance is a major factor of failure. Retrospective studies have established a link between baseline resistance and evolution of viral load in pretreated patients.Two prospective studies have shown promising results of resistance testing in the choice of salvage regimen. The clinical utility of resistance testing becomes more and more obvious although some difficulties due to the interpretation of the test or to technical limitations still arise. A correlation between protease inhibitor plasma levels and HIV RNA course has been established. Protease inhibitors seem to be good candidate for therapeutic drug monitoring. As for resistance testing, there are a lot of unresolved issues, but the combination of resistance testing and therapeutic drug monitoring is the first step toward a global approach of HIV treatment taking into account the right drug at the appropriate concentration.