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 with an optimized background regimen according to genotypic and phenotypic resistance testing. This favorable situation has been accomplished by the advent of new compounds in already known drug classes (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 tools have been developed to better predict virologic response and tolerability of a given regimen in the individual patient, such as weighted mutation scores, virtual phenotypes, viral tropism assays, pharmacogenetics and pharmacokinetic analyses. This new array of therapeutic and diagnostic tools requires a highly specialized training of the treating physician to achieve the ultimate goal of halting disease 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 by new diagnostic tools.