Approved HIV reverse transcriptase inhibitors in the past decade

Acta Pharm Sin B. 2022 Apr;12(4):1567-1590. doi: 10.1016/j.apsb.2021.11.009. Epub 2021 Nov 16.

Abstract

HIV reverse transcriptase (RT) inhibitors are the important components of highly active antiretroviral therapies (HAARTs) for anti-HIV treatment and pre-exposure prophylaxis in clinical practice. Many RT inhibitors and their combination regimens have been approved in the past ten years, but a review on their drug discovery, pharmacology, and clinical efficacy is lacking. Here, we provide a comprehensive review of RT inhibitors (tenofovir alafenamide, rilpivirine, doravirine, dapivirine, azvudine and elsulfavirine) approved in the past decade, regarding their drug discovery, pharmacology, and clinical efficacy in randomized controlled trials. Novel RT inhibitors such as islatravir, MK-8504, MK-8507, MK8583, IQP-0528, and MIV-150 will be also highlighted. Future development may focus on the new generation of novel antiretroviral inhibitors with higher bioavailability, longer elimination half-life, more favorable side-effect profiles, fewer drug-drug interactions, and higher activities against circulating drug-resistant strains.

Keywords: 3TC, (−)-2′,3′-dideoxy-3′-thiacytidine (common name, lamivudine); ABC, abacavir; ATV, atazanavir; AZT, 3′-azido-3′-deoxy-thymidine (common name, zidovudine); BIC, bictegravir; CAB, cabotegravir; CC50, the 50% cytotoxic concentration; COBI, cobicistat; Clinical efficacy; DOR, doravirine; DPV, dapivirine; DRV, darunavir; DTG, dolutegravir; EACS, European AIDS Clinical Society; EC50, half maximal effective concentration; EFV, efavirenz; ESV, elsulfavirine; EVG, elvitegravir; F, bioavailability; FDA, US Food and Drug Administration; FTC, (−)-2′,3′-dideoxy-5-fluoro-3′-thiacytidine (common name, emtricitabine); HAART; HAART, highly active antiretroviral therapy; HIV treatment; HIV, human immunodeficiency virus; IAS-USA, International Antiviral Society-USA; IC50, half maximal inhibitory concentration; MSM, men who have sex with men; NNRTI; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; t1/2, elimination half-life.

Publication types

  • Review