Antiretroviral salvage therapy for multiclass drug-resistant HIV-1-infected patients: from clinical trials to daily clinical practice.

Drug resistance is one of the key problems in the management of long-term HIV-1-infected patients. Due to cross-resistance patterns within classes, broad resistance to the three original antiretroviral classes can develop in some patients, mainly those with extensive antiretroviral treatment experience and multiple treatment failures. Triple-class-resistant HIV-1 infection has been associated with a higher risk of clinical progression and death. Additionally, it increases the probability of transmission of multidrug-resistant HIV-1 strains. Over the last years, the availability of new antiretroviral agents against novel targets (integrase inhibitors and CCR5 antagonists), and new drugs within old classes (nonnucleoside reverse transcriptase inhibitors and protease inhibitors) has opened a range of new therapeutic options for patients with multiclass drug-resistant HIV-1 infection and scarce therapeutic options with previous drugs. In randomized clinical trials, each of these new drugs has shown exceptional efficacy results, especially in patients who received other fully active drugs in the regimen. Indeed, in nonrandomized trials and observational studies, unprecedented rates of virologic suppression similar to those obtained in naive patients have been achieved when three of the currently available new drugs were combined, even in heavily experienced patients who had no viable salvage options with the previous classes. Thus, the goal of suppression and maintenance (plasma HIV-1 RNA < 50 copies/ml) is now also attainable in patients with multidrug-resistant HIV-1 infection. Treatment failure can still occur, however, and the management of patients with multidrug-resistant HIV-1 infection remains a challenge. Clinicians are encouraged to optimize use of the new drugs to obtain better control of HIV infection while avoiding emergence of new resistance-associated mutations. The aim of this article is to summarize current knowledge on the management of salvage therapy for patients with multidrug-resistant HIV-1 infection by analyzing the evidence extracted from clinical trials, and to review the information on the effectiveness of triple combinations of new drugs provided by non-comparative trials and observational studies.