US-12616692-B2 - Method of achieving HIV viral remission using long-acting antiretroviral agents

US12616692B2US 12616692 B2US12616692 B2US 12616692B2US-12616692-B2

Abstract

A method of achieving HIV viral remission in a patient in need thereof, comprising the steps of: after exposure of the patient to the HIV virus, administering an early antiretroviral therapy (eART) of therapeutically effective amounts of cabotegravir and rilpivirine long-acting antiretrovirals, and after eART suppression of the virus, discontinuing said early antiretroviral therapy.

Inventors

Michele B. DALY
Jose Gerardo Garcia Lerma
Walid M. Heneine
William Robert SPREEN
Peter Evan Owen WILLIAMS

Assignees

VIIV HEALTHCARE COMPANY
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

Dates

Publication Date: 20260505
Application Date: 20210630

Claims (11)

1 . A method of achieving HIV viral remission in a patient in need thereof, comprising the steps of: after exposure of the patient to the HIV virus, administering to said patient an early antiretroviral therapy (eART) of therapeutically effective amounts of cabotegravir and rilpivirine long-acting antiretrovirals, and after eART suppression of the HIV virus, discontinuing said early antiretroviral therapy.
2 . The method of claim 1 , wherein the early antiretroviral therapy is initiated within 2 weeks after exposure of the patient to the HIV virus.
3 . The method of claim 1 , wherein the early antiretroviral therapy is initiated while the patient has >500CD4+ cells/ml.
4 . The method of claim 1 , wherein early antiretroviral therapy further comprises administering one or more additional antiretroviral agents.
5 . The method of claim 4 , wherein the one or more additional antiretroviral agents comprises emtricitabine (FTC) and/or tenofovir or a prodrug thereof.
6 . The method of claim 4 , wherein early antiretroviral therapy further comprises administering to said patient a latency reversing agent.
7 . The method of claim 6 , wherein said latency reversing agent is a TLR7 agonist.
8 . The method of claim 7 , wherein the TLR7 agonist is vesatolimod.
9 . A method of achieving HIV viral remission in a patient in need thereof comprising administering to said patient early antiretroviral therapy (eART) of cabotegravir and rilpivirine long-acting antiretrovirals.
10 . The method of claim 1 , wherein the early antiretroviral therapy is initiated while the patient has >350CD4+ cells/ml.
11 . The method of claim 1 , wherein the early antiretroviral therapy is initiated while the patient has >200CD4+ cells/ml.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a § 371 national phase entry of International Application No. PCT/IB2021/055874, filed 30 Jun. 2021, which claims the benefit of U.S. Provisional Application No. 63/047,513, filed 2 Jul. 2020. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH This invention was made with Government support under project number 1845 and Cooperative Research Agreement Number D-588-16 by the Centers for Disease Control and Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of HIV/AIDS Prevention. The Government has certain rights in the invention. FIELD OF THE INVENTION The invention relates to the prevention or treatment of Human Immunodeficiency Virus (HIV) infection. In particular, the invention relates to a process for achieving partial or complete remission of an HIV infection where treatment is initiated early with a combination regimen containing long-acting antiretroviral drugs with or without a latency reversal agent. BACKGROUND TO THE INVENTION Among viruses, human immunodeficiency virus (HIV), a kind of retrovirus, is known to cause acquired immunodeficiency syndrome (AIDS). Potent, combination antiretroviral therapy (cART) has revolutionized the care of pateints with HIV infection. Cure of the HIV infection, such that cART would no longer be required, has been elusive because of the persistence of both low-level viremia and a long-lived reservoir of latently-infected cells mostly consisting in memory CD4+ T cells with proviruses capable of being activated to produce infectious viruses. Hong F F. AIDS Rev. 2015; 17 (2): 71-82. It has been general practice to defer the initiation of antiretroviral therapy in asymptomatic patients with a CD4+ count above a certain threshold level. De Cock K M., N Engl J Med 2013; 368:886-889. The effect of the timing of the initiation of antiretroviral therapy on clinical and microbiologic outcomes has been controversial in evaluations of the benefit of therapy and of the associated short- and long-term complications and costs. For many years, antiretroviral therapy was delayed until a patient's CD4+ count fell below 200 cells per cubic millimeter, which led to frequent opportunistic infections. Severe P., N Engl J Med. 2010 Jul. 15; 363 (3): 257-65. Retrospective analyses of patients with HIV-1 infection who were treated in developed countries have suggested a benefit from early antiretroviral therapy (eART). Cohen M S., N Engl J Med. 2011; 365 (6): 493-505. These data, along with observational studies, provide strong evidence for the initiation of antiretroviral therapy in patients with higher CD4+ cells per cubic millimeter. Lundgren J., N Engl J Med. 2016; 374 (4): 394. Achieving a combination antiretroviral therapy that is administered at an early antiretroviral therapeutic time point and reduces low-level viremia and the reservoir of latently-infected cells is desirable. Combination antiretrovial therapy has yet to find the composition that accomplishes the above mentioned criteria that would ultimately result in a patient being able to stop antiretroviral therapy either through remission or cure. As such, there is a need in the art for an antiretroviral therapy that effectively treats HIV by further reducing low-level viremia and the latent reservoir of CD4+ cells that are capable of reintroducing infectious virus into the host. SUMMARY OF THE INVENTION Methods are disclosed herein for achieving virologic remission (also referred to as functional cure) in a primate host infected by an immunodeficiency virus without the necessity of continued treatment with antiviral agents. Remission is demonstrated by the lack of virus rebound in plasma after discontinuation of suppressive antiretroviral therapy. Remission is achieved when treatment is initiated within days or weeks after acute exposure with a combination regimen that contains long-acting antiretroviral (ARVs) drugs. Here, we demonstrate virologic remission with a combination regimen containing a pharmacologically effective amount of the integrase inhibitor cabotegravir long-acting (CAB-LA), and a pharmacologically effective amount of the nonnucleoside reverse transcriptase inhibitor rilpivirine long-acting (RPV-LA). Treatment is effective if initiated within days or weeks after acute exposure. In the specific description, virus remission is achieved when treatment is discontinued after a period of sustained viral suppression. The discovery informs a new biomedical approach to achieving functional virologic remission and potentially cure of HIV. Early antiretroviral therapy or eART improves clinical outcomes by reducing the size and diversity of the viral reservoir, limiting immune damage and delaying viral rebound after treatment interruption. Latency reversing agents, or LRAS, activate the viral reservoir. Virally suppressed individuals have been treated with LRAs in attempt to purge latent virus for the ‘shock and kill’ strat