Related Experiment Video
Updated: Jul 3, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Improving non-nucleoside reverse transcriptase inhibitors for first-line treatment of HIV infection: the development
Zachary K Sweeney1, Klaus Klumpp
1Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. zachary.sweeney@roche.com
Abstract:
Efavirenz non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy or boosted protease inhibitor (PI)-based therapy are currently recommended as first-line regimens for the treatment of HIV infection. Although the available therapy options are efficacious and well-tolerated in the majority of patients, treatment durability is still limited by drug-related side effects, inadequate patient adherence and the development of drug resistance. PI-based regimens have higher tablet loads, more complicated drug interactions and have been associated with gastrointestinal side effects and metabolic abnormalities. NNRTI-based regimens are efficacious, but have a low genetic barrier to resistance and have been associated with rash, hypersensitivity reactions and central nervous system side effects. There is, therefore, still a need for first-line antiviral agents that facilitate patient adherence and allow durable suppression of viral replication. The next-generation NNRTIs in development include rilpivirine (TMC-278), UK-453061, RDEA-806, IDX-899 and MK-4965. These NNRTIs demonstrate significant advantages over efavirenz, and may improve treatment options for first-line therapy. A number of other structurally diverse compounds that inhibit common NNRTI-resistant mutant viruses are also under investigation. In this review, the desirable features of a next-generation NNRTI for treatment-naïve patients are discussed, as well as the properties of the NNRTIs that are currently in development.
Related Concept Videos
Antiviral Nucleoside Inhibitors
Retrovirus Life Cycles
Inhibitors of Virion Maturation and Assembly
Inhibitors of Viral Protein Synthesis
Inhibitors Of Virion Release
Viruses with RNA Genomes

