Resistance analyses in HIV infected patients with a history of multiple antiretroviral treatment regimens

Objective: To assess HIV-1 isolate based resistance profiles from extensive ly pretreated patients and effects of a resistance guided switch of antiret roviral therapy. Methods: In a prospective study phenotypic and genotypic resistance analyse s were performed on HIV infected individuals with failure of the current th erapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyt e counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks. Results: All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations a nd phenotypic resistance to AZT and 3TC were found in over 80% of individua ls; resistance to DDI and D4T was detected in less than 10% of cases. A res istance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or mo re drugs compared with patients with resistance to less than two drugs of o ngoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patie nts with resistance to at least two drugs in the previous regimen. Conclusions: Among different RTI, the profile of clinically relevant resist ance indicates pronounced differences when looking at separate drugs. Regar ding virological response, in the context of available drugs, resistance te sted with currently used methods is of limited value in extensively pretrea ted patients and seems to have its value primarily in first or second switc h of therapy.