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.
Highlights
In spite of considerable success in the treatment of acquired immune deficiency syndrome (AIDS), combination antiretroviral therapies, known as highly active antiretroviral therapies (HAARTs), still face challenges in long-term safety, regimen adherence, and the emergence of drug resistance
First-line combination antiretroviral therapies (cARTs) have generally consisted of two nucleoside/nucleotide reverse transcriptase (RT) inhibitors (NRTIs) and one inhibitor in another class, such as a non-nucleoside RT inhibitor (NNRTI), an IN strand transfer inhibitor (INSTI), or a pharmacologically-boosted protease inhibitor (PI) [15,28,29]
New formulations are needed that are safer and support greater adherence, because long-term treatment with cART has been associated with a variety of comorbidities [30,31,32,33,34,35,36,37,38,39], as well as non-adherence that leads to drug resistance and virologic failure [40,41]
Summary
In spite of considerable success in the treatment of acquired immune deficiency syndrome (AIDS), combination antiretroviral therapies (cARTs), known as highly active antiretroviral therapies (HAARTs), still face challenges in long-term safety, regimen adherence, and the emergence of drug resistance. Most cART regimens target at least two of three HIV enzymes that are essential for viral replication: reverse transcriptase (RT), integrase (IN), and protease (PR) [15,16,17]. For patients with multi-class, drug-resistant HIV infections, other stages of the HIV life cycle have been targeted, such as the CCR5 receptor and gp41-mediated viral fusion to the host cell [11,15]. This article reviews the efficacy, safety, adherence, a summary of emergent drug resistance, and possible future trends for these NNRTI/INSTI cARTs in the treatment of AIDS
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
