Citation

Himmel DM, Arnold E. Pharmaceuticals (Basel) 2020; 13(6): 1-26.

Copyright

(Copyright © 2020, MDPI)

DOI

10.3390/ph13060122

PMID

unavailable

Abstract

In the treatment of acquired immune deficiency syndrome (AIDS), the diarylpyrimidine (DAPY) analogs etravirine (ETR) and rilpivirine (RPV) have been widely effective against human immunodeficiency virus (HIV) variants that are resistant to other non-nucleoside reverse transcriptase inhibitors (NNRTIs). With non-inferior or improved efficacy, better safety profiles, and lower doses or pill burdens than other NNRTIs in the clinic, combination therapies including either of these two drugs have led to higher adherence than other NNRTI-containing treatments. In a separate development, HIV integrase strand transfer inhibitors (INSTIs) have shown efficacy in treating AIDS, including raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), bictegravir (BIC), and dolutegravir (DTG). Of these, DTG and BIC perform better against a wide range of resistance mutations than other INSTIs. Nevertheless, drug-resistant combinations of mutations have begun to emerge against all DAPYs and INSTIs, attributable in part to non-adherence. New dual therapies that may promote better adherence combine ETR or RPV with an INSTI and have been safer and non-inferior to more traditional triple-drug treatments. Long-acting dual-and triple-therapies combining ETR or RPV with INSTIs are under study and may further improve adherence. Here, highly resistant emergent mutations and efficacy data on these novel treatments are reviewed. Overall, ETR or RPV, in combination with INSTIs, may be treatments of choice as long-term maintenance therapies that optimize efficacy, adherence, and safety. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Language: en

Keywords

human; Review; nephrotoxicity; insomnia; liver failure; suicidal ideation; depression; suicide attempt; suicidal behavior; treatment outcome; HIV; comorbidity; rhabdomyolysis; lamivudine; mental disease; cholesterol blood level; lipid metabolism; triacylglycerol; automutilation; Human immunodeficiency virus infection; sleep disorder; drug structure; nonhuman; drug safety; efavirenz; drug efficacy; drug tolerability; drug withdrawal; low density lipoprotein cholesterol; cardiovascular disease; proteinuria; myopathy; peripheral neuropathy; Human immunodeficiency virus; drug approval; Adherence; paresthesia; ritonavir; lactic acidosis; dizziness; unspecified side effect; emtricitabine; virus load; triacylglycerol blood level; outcome assessment; CD4 lymphocyte count; binding site; proteinase inhibitor; treatment duration; lipodystrophy; abacavir; atazanavir; hyperbilirubinemia; mitochondrial toxicity; tenofovir disoproxil; integrase inhibitor; raltegravir; antiviral resistance; etravirine; nonnucleoside reverse transcriptase inhibitor; atazanavir plus ritonavir; rilpivirine; darunavir; efavirenz plus emtricitabine plus tenofovir disoproxil; dolutegravir; Drug resistance; Dolutegravir; elvitegravir; estimated glomerular filtration rate; abacavir plus dolutegravir plus lamivudine; cabotegravir; CD8 lymphocyte count; darunavir plus ritonavir; dolutegravir plus rilpivirine; doravirine; Dual therapy; Etravirine; Integrase strand transfer inhibitor; lack of drug effect; Long-acting therapy; Non-nucleoside reverse transcriptase inhibitor; Rilpivirine