For months, we've been excited about emerging data regarding GSK744 (also known as "744"), an investigational integrase inhibitor, close cousin of dolutegravir (Tivicay, DTG), with the potential for once-monthly injection dosing and promise in pre-exposure prophylaxis (PrEP) -- at least in rectally-exposed monkeys. Indeed, adherence concerns remain prominent in both of these therapeutic areas, concerns that could be readily addressed by directly observed, injectable treatments.

Data presented at CROI 2014 continued to fuel this fire. First, investigators showed that once-monthly injections of 744 provided 100% protection (in monkeys) from repeated intravaginal challenge from SHIV.

Next, results from the phase-2 LATTE study showed that initial treatment (24 weeks) with two nucleoside reverse transcriptase inhibitors (NRTIs) plus 744 followed by maintenance therapy with daily oral 744 plus rilpivirine (Edurant) was able to maintain 48-week viral suppression (82%) at least as well as a two-NRTI-plus-efavirenz regimen (71%).

LATTE's results are interesting on a couple of fronts. First, this study paves the way for a fully powered phase-3 induction-maintenance regimen of fully injectable, once-monthly medications. One individual did have virus with emergent integrase resistance with the point mutation Q148R and rilpivirine resistance (E138K), indicating that we will have to watch this participant closely in future studies. It was reassuring to know that the participant was randomized to the lowest 744 dose (10 mg/day) and was also eating an extremely low-calorie diet, which could have caused rilpivirine malabsortion.

LATTE is also another study showing the promise of NRTI-sparing treatment (this time, in maintenance, rather than initial therapy as seen in the NEAT 001 study). GSK744 and rilpivirine are a forced dancing couple, because they are the only current antiretrovirals that allow nanoformulation, but dolutegravir and rilpivirine are available and have no pharmacokinetic interactions.

The space for oral antiretroviral medications is becoming crowded and mature, portending a decline in new drug discovery. Yet, the excitement about long-acting injectable antiretroviral therapy suggests that the benefits to adherence and acceptability of medications have not yet been fully realized, and the world for PrEP options is about to radically change.

Which other studies presented at CROI 2014 will have lasting impact? Read more of Dr. Llibre and Dr. Young's top picks.