Efficacy and resistance of recently developed non-nucleoside reverse transcriptase inhibitors for HIV-1

Since the introduction of the HAART, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have played an essential role in treating HIV: their strong antiviral potency, good metabolic profile and low pill burden make them an ideal option in the design of an optimized triple drug regimen. Nonetheless, the currently approved NNRTIs (efavirenz and nevirapine) are weighed by peculiar toxicities, while a low genetic barrier and the development of cross-resistance significantly limits their use in cases of suboptimal adherence. Many drugs are in development and they are all designed with the aim to overcome resistance problems. In this review we present data on virological efficacy and resistance profiles of some of the most promising new molecules: some (such as rilpivirine) are close to being marketed, others are in Phase II trials (IDX899 and RDEA806), others again have just completed preclinical studies and are having their first clinical evaluations (RO-5028, UK-453061 and BILR-355 BS); etravirine is already approved by the US FDA, but it is still not licensed in Europe. Other new molecules (Merck MK-4965, GlaxoSmithKline GW678284 and a pyridazinone derivative by Roche), which are currently in early-development phases, are also briefly described