The successes and failures of HIV drug discovery

Abstract

Introduction: To date, several anti-human immunodeficiency virus (HIV) drugs, including reverse transcriptase inhibitors and protease inhibitors, have been developed and used clinically for the treatment of patients infected with HIV. Recently, novel drugs have been discovered which have different mechanisms of action from those of the above inhibitors, including entry inhibitors and integrase (IN) inhibitors; the clinical use of three of these inhibitors has been approved. Other inhibitors are still in development.

Areas covered: This review article summarizes the history of the development of anti-HIV drugs and also focuses on successes in the development of these entry and IN inhibitors, along with looking at exploratory approaches for the development of other inhibitors.

Expert opinion: Currently used highly active antiretroviral therapy can be subject to a loss of efficacy, due to the emergence of multi-drug resistant (MDR) strains; a change of regimens of the drug combination is required to combat this, along with careful monitoring of the virus and CD4 in the blood, by methods such as cellular tropism testing. In such a situation, entry inhibitors such as CCR5/CXCR4 antagonists, CD4 mimics, fusion inhibitors and IN inhibitors might be optional agents for an expansion of the drug repertoire available to patients at all stages of HIV infection.

Keywords:

• AIDS
• CCR5
• CD4 mimic
• chemokine receptor
• CXCR4
• fusion
• HIV
• integrase

Acknowledgements

The authors wish to acknowledge their collaborators: N Fujii (Kyoto University), N Yamamoto (National University of Singapore), T Murakami (National Institute of Infectious Diseases), H Nakashima (St. Marianna University), H Mitsuya (Kumamoto University), T Hattori (Tohoku University), M Waki (Kyushu University), A Otaka (The University of Tokushima), I Hamachi (Kyoto University), M Matsuoka (Kyoto University), S Matsushita (Kumamoto University), K Yoshimura (Kumamoto University), S Harada (Kumamoto University), JO Trent (University of Louisville), SC Peiper (Medical College of Georgia), Z Wang (Medical College of Georgia), H Xiong (University of Nebraska Medical Center), S Kusano (St. Marianna University), S Terakubo (St. Marianna University), A Ojida (Kyoto University), S Oishi (Kyoto University), S Ueda (Kyoto University), J Komano (National Institute of Infectious Diseases), E Kodama (Tohoku University), K Ohba (National University of Singapore), E Urano (National Institute of Infectious Diseases), K Maddali (National Cancer Institute), Y Pommier (National Cancer Institute), JA Beutler (National Cancer Institute), A Iwamoto (The University of Tokyo), H Tsutsumi (Tokyo Medical and Dental University), N Ohashi (Tokyo Medical and Dental University), K Hiramatsu (Kyoto University), T Araki (Kyoto University), T Ogawa (Kyoto University), H Nishikawa (Kyoto University), Y Tanabe (Tokyo Medical and Dental University), T Nakahara (Tokyo Medical and Dental University), H Arai (Tokyo Medical and Dental University), T Ozaki (Tokyo Medical and Dental University), A Sohma (Tokyo Medical and Dental University) and B Evans (Medical College of Georgia), A Omagari (Kyoto University), A Esaka (Kyoto University), M Nakamura (Kyoto University), Y Yamada (Tokyo Medical and Dental University), A Ohya (Tokyo Medical and Dental University), C Ochiai (Tokyo Medical and Dental University), A Ogawa (Tokyo Medical and Dental University) and K Itotani (Tokyo Medical and Dental University).

Notes

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