Clinical targeting of HIV capsid protein with a long-acting small molecule

@article{Link2020ClinicalTO,
  title={Clinical targeting of HIV capsid protein with a long-acting small molecule},
  author={John O. Link and Martin S. Rhee and Winston C. Tse and Jim Zheng and John R. Somoza and William Rowe and Rebecca Begley and Anna Chiu and Andrew S Mulato and Derek Hansen and Eric Singer and Luong K. Tsai and Rujuta A. Bam and Chien-Hung Chou and Eda Canales and Gediminas J. Brizgys and Jennifer R. Zhang and Jiayao Li and Michael Graupe and Philip Anthony Morganelli and Qi Liu and Qiaoyin Wu and Randall L. Halcomb and R. Saito and Scott D. Schroeder and Scott E. Lazerwith and Steven S. Bondy and Debi Jin and Magdeleine Hung and Nikolai Novikov and Xiaohong Liu and Armando G. Villaseñor and Carina E. Cannizzaro and Eric Hu and Robert L. Anderson and Todd C. Appleby and Bing Lu and Judy Mwangi and Albert C Liclican and Anita Niedziela-Majka and Giuseppe A. Papalia and Melanie H. Wong and Stephanie A. Leavitt and Yili Xu and David Koditek and George J Stepan and Helen Yu and Nikos C. Pagratis and Sheila Clancy and Shekeba Ahmadyar and Terrence Cai and Scott Sellers and Scott Alan Wolckenhauer and John Ling and C. Callebaut and Nicolas A Margot and Renee R Ram and Yapei Liu and Robert H. Hyland and Gary I. Sinclair and Peter Ruane and Gordon E. Crofoot and Cheryl Mcdonald and Diana M. Brainard and Latesh Lad and Swami Swaminathan and Wesley I. Sundquist and Roman Sakowicz and Anne E. Chester and William E. Lee and Eric S Daar and Stephen R Yant and Tomas Cihlar},
  journal={Nature},
  year={2020},
  pages={1-5}
}
Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis 1 – 5 . However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance 6 . In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment—which contributes to virologic failure, resistance generation and viral… 

Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention

  • Y. Kim
  • Biology, Medicine
    Infection & chemotherapy
  • 2021
This review summarizes the data of efficacies and safety profiles of LA CAB with RPV regimen, and also new long-acting injectable antiretroviral agents in pipeline.

Long-acting antiretrovirals: a new era for the management and prevention of HIV infection

The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.

Structural and mechanistic bases for a potent HIV-1 capsid inhibitor

It is found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells, providing a platform for the rational development of improved long-acting therapies.

Structural and Mechanistic Bases of Viral Resistance to HIV-1 Capsid Inhibitor Lenacapavir

High resolution structures of the main drug resistant capsid variants are determined, which provide mechanistic insight into the viral resistance to LEN, and an improved inhibitor is developed, which exhibited enhanced activity against the viral Q67H/N74D capsid phenotype compared with that of parental LEN.

HIV-1 Maturation: Lessons Learned from Inhibitors

The development and therapeutic potential of maturation inhibitors (MIs), an experimental class of anti-HIV-1 compounds with mechanisms of action distinct from those of the PR inhibitors, are reviewed.

Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection.

In patients with multidrug-resistant HIV-1 infection, patients who received lenacapavir had a greater reduction from baseline in viral load than those who received placebo.

Novel and Investigational HIV Therapies for Treatment and Prevention: Focus on Cabotegravir, Islatravir, and Lenacapavir

Clinical data have supported long-acting cabotegravir’s approval for treatment and pre-exposure prophylaxis of HIV while islatravir and lenacapavir remain in investigation status.

Long-acting injectable HIV therapies: the next frontier: Republication

Despite evidence that suggests that these therapies are efficacious and acceptable to patients, the challenge of integrating these agents into the current healthcare infrastructure and making these novel agents cost-effective and available to the populations most likely to benefit remains.
...

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