There's been a lot of interest recently in nucleoside-sparing, or nuke-sparing, regimens. The NEAT study compared boosted darunavir plus raltegravir, what was thought to be an excellent candidate for a nuke-sparing regimen, with a standard boosted darunavir plus tenofovir/emtricitabine.
The nuke-sparing regimen seemed to perform well; however, upon deeper analysis, "if you looked at those patients who are hardest to treat, those especially with low CD4 counts, some degree of high viral loads, you saw the nuke-sparing regimen didn't perform as well as the standard regimen, for reasons that are completely unknown," Gallant said.
The MODERN study looked at maraviroc (Selzentry, Celsentri) plus boosted darunavir. However, this study was stopped early because it was inferior to the standard regimen of boosted darunavir plus tenofovir/emtricitabine.
On the other hand, studies like GARDEL and OLE both found nuke-sparing regimens to be noninferior to standard regimens.
Ultimately, these studies suggest that a boosted PI taken with either an integrase inhibitor or maraviroc does not perform as well, usually because of high viral loads or low CD4 counts, according to Gallant.
"In contrast, you have boosted PIs combined with reverese transcriptase inhibitors where things look significantly different and better," Gallant said. "All I can conclude then is maybe the best nuke-sparing regimens have nukes in them."