Elvitegravir is more potent than Isentress (raltegravir) on resistant viral isolates T66I, L74M, E92Q, F121Y, Q148K, S153Y, and N155H. This should result in greater durability of elvitegravir provided there has not been prior use of Isentress. pubs.acs.org
In practice elvitegravir will be widely used at the 800 mg bid dosing first trialed to avoid the use of a ritonavir-like drug, even though much effort has been put into developing GS9350.
Patient tolerability of ritonavir is quite low, less than 75%, and most who "tolerate" the drug are happier without it. Gilead has refused to comment on the tolerability and side-effect profile of GS9350 alone. Another ritonavir competitor developed by Sierra Pharmaceuticals is described as "well tolerated" with the common side-effects being nausea, vomiting, severe headaches and diarrhea - similar to the list associated with ritonavir.
The FDA would prefer a ritonavir-like enzyme substrate, but there is little urgency in this as there is no evidence that the low doses of ritonavir used provides a signififcant enough barrier to exert selection pressure.
The clinical use of these drugs is highly divergent from the labelling and advertising.
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