The nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are small molecules that bind to HIV-1 RT at a site distinct from the DNA polymerase active site of the enzyme and block retroviral reverse transcription via an allosteric mechanism of action (1). Nevirapine (NVP) was the first NNRTI approved in 1996 by the US Food and Drug Administration for the treatment of HIV-1 infection, followed by delavirdine in 1997, efavirenz (EFV) in 1998, etravirine (ETV) in 2008, and rilpivirine (RPV) in 2011. For almost 20 y NNRTIs served as the cornerstone of combination antiretroviral therapy (cART). Indeed, most first-line cART included one NNRTI (typically NVP, EFV, or RPV) in combination with two nucleoside/nucleotide RT inhibitors. Just last month, RPV and the integrase inhibitor dolutegravir were approved as the first once-daily, single-pill, two-drug regimen for the maintenance treatment of virologically suppressed HIV-1 infection. ETV can be included in salvage cART for the treatment of HIV-1–infected ART-experienced individuals, including those with prior NNRTI exposure. NNRTIs have also been used to prevent HIV-1 infection. NVP has been used to prevent mother-to-child transmission (2), the …

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非核苷逆转录酶抑制剂的未来

非核苷逆转录酶（RT）抑制剂（NNRTIs）是与HIV-1 RT结合的小分子，该位点与酶的DNA聚合酶活性位点不同，并通过变构作用机制阻止逆转录病毒逆转录（1）。奈韦拉平（NVP）是美国食品药品监督管理局于1996年批准的第一项用于治疗HIV-1感染的NNRTI，其次是1997年的地拉夫定，1998年的依非韦伦（EFV），2008年的依曲韦林（ETV）和rilpivirine（ RPV）在2011年。近20年来，NNRTI一直是联合抗逆转录病毒疗法（cART）的基石。实际上，大多数一线cART包括一种NNRTI（通常为NVP，EFV或RPV）与两种核苷/核苷酸RT抑制剂的组合。就在上个月，RPV和整合酶抑制剂dolutegravir被批准为第一种每日一次的单药，维持病毒学抑制的HIV-1感染的两药疗法。ETV可以包括在挽救性cART中，用于治疗受HIV-1感染的ART经验丰富的个体，包括那些先前有NNRTI暴露的个体。NNRTIs也已用于预防HIV-1感染。NVP已被用来防止母婴传播（2），...