Extensive multi-drug resistance has not become nearly as prevalent as some experts predicted in the early 2000s. But it does happen -- and when it does, it's a serious problem.
"These patients are rare, but they are a cause of great consternation for those of us who manage them, because it's very unusual not to have [antiretroviral] options," Sax said.
Offering some hope is the attachment inhibitor BMS-663068 (or "068" for short), which binds to the gp120 on HIV's surface. Unlike the attachment inhibitor maraviroc (Selzentry, Celsentri), 068 is tropism agnostic. Even better, in vitro testing has shown no evidence of cross-resistance between 068 and any other antiretroviral class, Sax said. Efficacy and safety have also looked promising in early monotherapy trials, he noted.
One caveat with 068 is that roughly 5% of the HIV-1-infected patient population appears to have a variant of HIV that makes the drug "intrinsically inactive," Sax said. Once predictors have been determined, Sax suggested that some sort of pre-treatment assessment of drug susceptibility will be necessary.
A Phase 3 study of 068 is being planned, but "it is going to be very, very challenging, of course, to find patients who are eligible for this study," Sax said. "I hope they have very, very broad inclusion criteria, because these are difficult patients to treat, they have no other options, and there isn't a whole lot coming soon in this area."