Treatment of Heavily Antiretroviral-Experienced HIV-Infected Patients

In 2008, the goal of antiretroviral therapy is the suppression of viral load to undetectable levels(< 50 HIV-RNA copies/ml) even in heavily pretreated patients harboring multidrug-resistant viruses.This ambitious goal can be achieved by combining at least two fully active antiretroviral drugs withan optimized background regimen according to genotypic and phenotypic resistance testing. Thisfavorable situation has been accomplished by the advent of new compounds in already known drugclasses (e.g. second-generation protease inhibitors and nonnucleoside reverse transcriptase inhibitors)as well as thanks to the development of new drug classes with a different mode of action (e.g.fusion inhibitors, integrase inhibitors, and coreceptor antagonists). Moreover, new diagnostic toolshave been developed to better predict virologic response and tolerability of a given regimen in theindividual patient, such as weighted mutation scores, virtual phenotypes, viral tropism assays, pharmacogeneticsand pharmacokinetic analyses. This new array of therapeutic and diagnostic toolsrequires a highly specialized training of the treating physician to achieve the ultimate goal of haltingdisease progression. The purpose of this review is to introduce the new drugs and drug classes,and discuss their safety and use in combination therapy of multidrug-resistant viruses, guided bynew diagnostic tools.