The nucleoside(tide) reverse transcriptase inhibitors (NRTIs) have traditionally been an important ââ?¬Ë?back-boneââ?¬â?¢ of an\r\nantiretroviral therapy (ART) regimen. However all agents have been associated with both short- and long-term toxicity.\r\nThere have also been concerns regarding the efficacy and safety of a treatment sequencing strategy in which those\r\nwith past exposure and/or resistance to one or more NRTIs are re-exposed to ââ?¬Ë?recycledââ?¬â?¢ NRTIs in subsequent\r\nART regimens. Newer, potent and possible safer, agents from various ART classes continue to become available.\r\nThere has therefore been growing interest in evaluating NRTI-sparing regimens. In this review, we examined studies of\r\nNRTI-sparing regimens in adult HIV-positive patients with varying degrees of ART experience. We found that in\r\ntreatment experienced patients currently on a failing regimen with detectable viral load, there now exists a\r\nrobust evidence for the use of NRTI-sparing regimens including raltegravir with a boosted-protease inhibitor\r\nwith or without a third agent. In those on a virologically suppressive regimen switching to a NRTI-sparing\r\nregimen or in those ART-naÃ?¯ve patients initiating an NRTI-sparing regimen, evidence is sparse and largely\r\ncomes from small exploratory trials or observational studies. Overall, these studies suggest that caution needs to be\r\nexercised in carefully selecting the right candidate and agents, especially in the context of a dual-therapy regimen, to\r\nminimise the risks of virological failure. There is residual toxicity conferred by the ritonavir boost in protease-inhibitor\r\ncontaining NRTI-sparing regimens. Fully-powered studies are needed to explore the place of N (t)RTI-sparing regimens\r\nin the sequencing of ART. Additionally research is required to explore how to minimise the adverse effects associated\r\nwith ritonavir-based pharmacoenhancement.
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