Boosted elvitegravir as part of a STR revealed promising results in two large trials, but caution is needed because of increased INI and NRTI resistance. A similar low genetic barrier to drug resistance upon failure was seen for elvitegravir. Raltegravir and elvitegravir based regimens showed comparable or superior immunological response compared to other regimens. Dolutegravir combined with abacavir/lamuvidine has been the first combination reported to be virologically and immunologically superior compared to an efavirenz-based regimen. No drug resistance was detected suggesting a high genetic barrier to resistance development. In this patient population, novel treatment strategies have been explored, such as the combination of INI with a PI, sparing the NRTIs. Individual studies are underpowered or failed to show superiority. Also the mITT, OT and AT-based meta-analysis failed to show significant odds ratios in favor of these nucleosidesparing regimens. For stronger conclusions, more data are needed. Currently a large trial evaluating this concept is underway. Switching from enfuvirtide to raltegravir resulted in high levels of durable suppression in several uncontrolled trials indicating that substitution of a low genetic barrier component of combination antiretroviral 960539-70-2 structure therapy by raltegravir in patients with documented or suspected drug resistance can be safely performed. In contrast, the switch from a high genetic barrier PI towards raltegravir in a similar population resulted in a unfavorable OR in the OT-based meta-analysis, and thus higher levels of therapy failure in the raltegravir arm. When adding the effect of adherence and tolerability, the unfavorable effect was less NVP-LBH589 evident. Two major studies revealed conflicting results possibly influenced by duration of suppression and documentation of treatment history. The results indicate that when switching virologically suppressed patients, individual patient management is needed to assess history of treatment failure, available resistance profiles and duration of the current suppressive regimens in order to perform a safe switch. One of the limitations of this systematic review and metaanalysis are potential variations in efficacy between the individual INIs compared in similar settings,
