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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Second generation HIV protease inhibitors against resistant virus
1Merck & Co., Inc., Merck Research Laboratories, Department of Medicinal Chemistry, R800-C307, PO Box 2000, Rahway, NJ 08809, USA +1 732 594 4392 ; +1 732 594 9473 ; Zhijian_lu@merck.com.
Expert Opinion on Drug Discovery
|March 19, 2013
Summary
Second-generation HIV protease inhibitors combat resistant viruses but require boosting agents, leading to toxicity. New protease inhibitors are needed to overcome resistance and reduce side effects.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- The global AIDS epidemic necessitates effective HIV treatments.
- First-generation HIV protease inhibitors show diminishing efficacy due to rapid viral resistance.
- Salvage therapy with multiple protease inhibitors has limited success due to cross-resistance and toxicity.
Purpose of the Study:
- To review advancements in second-generation HIV protease inhibitors.
- To address high-level resistance challenges in HIV treatment.
- To explore strategies against drug-resistant HIV variants.
Main Methods:
- Review of scientific literature and developments since 2000.
- Analysis of new therapeutic strategies for resistant HIV.
- Evaluation of second-generation protease inhibitor effectiveness.
Main Results:
- Second-generation protease inhibitors often require ritonavir boosting, increasing plasma drug levels.
- This boosting practice is associated with significant toxicities.
- High-level resistance remains a persistent challenge in HIV management.
Conclusions:
- Second-generation HIV protease inhibitors necessitate boosting agents, posing toxicity risks.
- There is an ongoing need for novel protease inhibitors effective against resistant HIV strains.
- Future third-generation protease inhibitors aim for high potency without boosting agents.
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