Expanding therapeutic options: lenacapavir + bictegravir as a potential treatment for HIV

ABSTRACT

Introduction

Treatment for people with HIV/AIDS has radically evolved since the introduction of the first antiretrovirals. One newly approved antiretroviral is lenacapavir, which targets the viral capsid. Lenacapavir is currently approved as a therapeutic addition for subjects who are treatment-experienced, and who have developed resistance to multiple antiretrovirals. It is available both as a daily oral tablet and a once every 6-month subcutaneous injection. It is currently undergoing clinical trials in combination with the integrase inhibitor bictegravir as a dual therapy option, both for treatment experienced and treatment naïve individuals.

Areas covered

We reviewed published articles, conference proceedings, and clinical trial databases to assess the current status of the research into lenacapavir and bictegravir. While the clinical trials are ongoing, with little published data to date, this combination shows promise for the treatment of both treatment experienced and naïve patients. We review the studies relevant to the pharmacokinetic/pharmacodynamic properties of the drugs.

Expert opinion

The new combination with bictegravir will be beneficial for treatment experienced patients, as it represents a dual therapy modality with high barriers of resistance. As a therapy for treatment naïve patients, its use is likely more niche, as other combinations are available.

KEYWORDS:

• Antiretroviral
• bictegravir
• capsid inhibitor
• HIV-1
• lenacapavir

Article highlights

• Antiretroviral therapy for people living with HIV has radically evolved over time

• Lenacapavir is a recently approved first in class capsid inhibitor which is currently approved for individuals with resistant virus who have failed other therapies

• Lenacapavir is currently undergoing clinical trials in combination with the integrase inhibitor bictegravir for both treatment naïve and treatment experienced individuals

• In ongoing clinical trials, this combination is both efficacious and well tolerated by individuals

• As a first in class medication, use of lenacapavir with bictegravir should be limited to individuals who have failed other therapies, rather than be used for newly diagnosed individuals, due to an excellent resistance profile and limited therapeutic options for treatment experienced patients

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Acknowledgments

We wish to thank Dr. Kirk Hevener for providing assistance with using the ChemDraw software.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Institute of Health (Grant DA042374).