Antibody-based strategies in HIV therapy

Kufel, Wesley D

doi:10.1016/j.ijantimicag.2020.106186

Cited by 15 publications

(14 citation statements)

References 25 publications

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“…In this same study, viral load rebounded to near baseline in all dosages around day 40 post-injection, highlighting a need for sustained treatment. No evidence of resistance or switched tropism was observed while only mild side effects were encountered with this medication, and it has been given a fast track status by the US Food and Drug Administration (FDA) ( 119 ).…”

Section: Mechanisms Of Targeting Ccr5 To Inhibit Hiv-1 Disease Progressionmentioning

confidence: 99%

Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy

et al. 2022

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Globally, human immunodeficiency virus type 1 (HIV-1) infection is a major health burden for which successful therapeutic options are still being investigated. Challenges facing current drugs that are part of the established life-long antiretroviral therapy (ART) include toxicity, development of drug resistant HIV-1 strains, the cost of treatment, and the inability to eradicate the provirus from infected cells. For these reasons, novel anti-HIV-1 therapeutics that can prevent or eliminate disease progression including the onset of the acquired immunodeficiency syndrome (AIDS) are needed. While development of HIV-1 vaccination has also been challenging, recent advancements demonstrate that infection of HIV-1-susceptible cells can be prevented in individuals living with HIV-1, by targeting C-C chemokine receptor type 5 (CCR5). CCR5 serves many functions in the human immune response and is a co-receptor utilized by HIV-1 for entry into immune cells. Therapeutics targeting CCR5 generally involve gene editing techniques including CRISPR, CCR5 blockade using antibodies or antagonists, or combinations of both. Here we review the efficacy of these approaches and discuss the potential of their use in the clinic as novel ART-independent therapies for HIV-1 infection.

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Section: Mechanisms Of Targeting Ccr5 To Inhibit Hiv-1 Disease Progressionmentioning

confidence: 99%

Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy

et al. 2022

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“…5 , 73 Ibalizumab is injected intravenously (IV) as a single loading dose of 2000 mg, followed by maintenance doses of 800 mg injected IV every 2 weeks. 73 , 74 …”

Section: Molecules With Suitable Characteristics For La-artmentioning

confidence: 99%

“…Moreover, if a maintenance dose is missed by 3 days or more, a loading dose has to be readministered, leading to potential discomfort for the patients. 74 Despite a shorter administration schedule compared with other LAI-ARTs, ibalizumab represents a novel opportunity for heavily treatment-experienced adults with multiresistant HIV infection.…”

Section: Molecules With Suitable Characteristics For La-artmentioning

confidence: 99%

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

Thoueille

Choong

Cavassini

et al. 2021

Journal of Antimicrobial Chemotherapy

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The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient’s weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients’ privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current ‘one-size-fits-all’ approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. 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.

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“…Further, mAb therapy may be especially appropriate for multi-drug resistant (MDR) HIV infection. 21 Ibalizumab is a licensed humanized IgG4 mAb product that acts as a CD4-directed post-attachment inhibitor and is currently approved for patients with MDR HIV infection. Patients receive a 2 g loading dose followed by 800 mg maintenance doses every 2 weeks, or approximately 20 g on an annual basis.…”

Section: Ibalizumab For Multi-drug Resistant Hiv Infectionmentioning

confidence: 99%

Emerging antibody-based products for infectious diseases: Planning for metric ton manufacturing

Whaley

Zeitlin

2021

Human Vaccines & Immunotherapeutics

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This review focuses on the emerging monoclonal antibody market for infectious diseases and the metric ton scale manufacturing requirements to meet global demand. Increasing access to existing antibodybased products coupled with the unmet need in infectious disease will likely exceed the current existing global manufacturing capacity. Further, the large numbers of individuals infected during epidemics such as the ongoing COVID-19 pandemic emphasizes the need to plan for metric ton manufacturing of monoclonal antibodies by expanding infrastructure and exploring alternative production systems.

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Antibody-based strategies in HIV therapy

Cited by 15 publications

References 25 publications

Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy

Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy

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

Emerging antibody-based products for infectious diseases: Planning for metric ton manufacturing

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