World AIDS Day 2023: New and Promising Treatments for HIV/AIDS

World AIDS Day 2023: New and Promising Treatments for HIV/AIDS

The World Health Organization (WHO) has designated the theme of World AIDS Day 2023 as “Let Communities Lead.”

Tomorrow is World AIDS Day 2023. Every December 1, the global community comes together to observe World AIDS Day. Originating in 1988, this day serves as a crucial platform for increasing awareness about human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and paying tribute to those whose lives have been impacted by the epidemic.

Over the last 35 years, substantial strides have been made in tackling HIV/AIDS, propelled by advancements in medical research, enhanced accessibility to treatment and prevention and a more comprehensive understanding of the virus.

World AIDS Day offers an occasion for reflection on the strides achieved thus far. It prompts us to acknowledge the remaining challenges in attaining the goal of ending AIDS by 2030 and calls on all stakeholders to intensify collaborative efforts for the success of the HIV response.

The World Health Organization (WHO) has designated the theme of World AIDS Day 2023 as “Let Communities Lead.” According to the WHO, this theme underscores the pivotal role communities have played in shaping the HIV response, emphasizing the need for community-driven approaches to address the challenges ahead.

According to the WHO, HIV continues to be a significant global public health concern, claiming the lives of 40.4 million individuals to date, with ongoing transmission occurring worldwide.

HIV is a viral infection that targets the body’s immune system, progressing to its most advanced stage known as AIDS. The virus attacks white blood cells, compromising the immune system and increasing susceptibility to diseases such as tuberculosis, infections and certain cancers.

HIV is transmitted through an infected person’s body fluids, including blood, breast milk, semen and vaginal fluids. Importantly, it is not transmitted through casual contact like kisses, hugs, or sharing food, although transmission from a mother to her baby is possible.

While there is no cure for HIV infection, access to effective prevention, diagnosis, treatment and care, including addressing opportunistic infections, has transformed HIV into a manageable chronic health condition. This enables individuals living with HIV to lead long and healthy lives.

Global entities such as the WHO, the Global Fund and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have developed comprehensive strategies aligned with Sustainable Development Goal (SDG) target 3.3, aiming to end the HIV epidemic by 2030.

New FDA-Approved Treatments For HIV

HIV treatment involves the administration of combined antiretroviral therapy (ART) to effectively suppress the viral load, maintain or enhance immune function and reduce the risk of opportunistic infections and cancers commonly associated with HIV.

In 2022, the US Food and Drug Administration (FDA) granted approval to the medication Sunlenca (lenacapavir) for adults living with multi-drug resistant HIV-1 infection. Developed by Gilead, Sunlenca is the first drug in a novel class known as capsid inhibitors to receive FDA approval for treating HIV-1. Its mechanism of action involves blocking the protein shell (capsid) of the HIV-1 virus, disrupting multiple crucial stages of the viral lifecycle.

The FDA’s endorsement of Sunlenca is backed by compelling clinical evidence, demonstrating its efficacy as a viable treatment option. In a study where the antiviral activity of Sunlenca was evaluated in combination with an optimized background regimen, 87.5 percent of patients receiving Sunlenca experienced a significant reduction in virus levels, compared to only 16.7 percent in the placebo group. Over 26 weeks of Sunlenca combined with other antiretroviral drugs, 81 percent of participants achieved HIV RNA suppression, reaching levels low enough to be considered undetectable. This suppression was sustained in 83 percent of participants after 52 weeks.

In 2021, the FDA approved Cabenuva (cabotegravir and rilpivirine, injectable formulation) as a comprehensive regimen for HIV treatment, intended to replace an existing antiretroviral regimen in individuals with virological suppression, a stable antiretroviral history and no record of treatment failure or known resistance to cabotegravir or rilpivirine. This marked the first FDA-approved injectable, complete regimen for HIV-infected adults, administered once a month.

The safety and efficacy of Cabenuva were established through two randomized, open-label, controlled clinical trials involving 1,182 HIV-infected adults who were virologically suppressed (HIV-1 RNA less than 50 copies/mL) before initiating Cabenuva treatment. Both trials concluded with maintained virologic suppression, and no clinically significant change from baseline in CD4+ cell counts was observed.

More Investigational Therapies for HIV Are on the Way

American Gene Technologies, a pioneering biotech company headquartered in Rockville, Maryland, has released promising results from its Phase I trial of AGT103-T, a gene therapy designed for individuals with chronic HIV disease. This candidate, derived from a person’s own genetically modified cells, aims to restore the Gag-specific CD4+ T cell response in those receiving antiretroviral therapy.

The Phase I clinical data revealed that Gag-specific CD4+ T cells were detected in all treated individuals, showing a substantial increase ranging from 9 to 300-fold compared to baseline within 14 days after the infusion of AGT103-T. Additionally, Gag-specific CD8+ T cells demonstrated an increase of 1.7 to 10-fold relative to baseline within 28 days after the cell product infusion.

Currently, a Phase II clinical trial is underway for AGT103-T, and data from this phase is anticipated to be available in 2024 to 2025. These findings signify a significant step forward in the development of AGT103-T as a potential gene therapy for HIV.

In 2021, the FDA granted approval to San Francisco-based Excision BioTherapeutics to start trials assessing CRISPR gene editing as a potential treatment for HIV. The noteworthy candidate, EBT-101, is designed to eliminate HIV proviral DNA using CRISPR-Cas9 along with two guide RNAs (gRNAs). These dual gRNAs target three specific sites within the HIV genome, facilitating the removal of substantial portions of the viral DNA and minimizing the potential for viral escape.

Distinguished as the first-in-human CRISPR-based one-time gene therapy under evaluation for individuals with HIV, the Investigational New Drug (IND) application for EBT-101 enables Excision to initiate a Phase I/II clinical trial. This trial aims to assess the safety, tolerability and efficacy of EBT-101, marking a significant advancement in the exploration of CRISPR technology for potential HIV treatment.

Promising HIV Vaccines in Clinical Trials

Advancements in preventable therapeutic options for HIV are currently in progress. In November 2023, Hookipa Pharma Inc., a company specializing in a new class of immunotherapeutics based on its proprietary arenavirus platform, announced FDA approval of its IND application for HB-500.

Preclinical data demonstrated that HB-500 was well-tolerated, eliciting robust, high-quality and enduring immune responses, including antigen-specific T cells and antibodies, in non-human primates. Notably, it significantly reduced viral load and clinical illness compared to a placebo. The Phase I trial for HB-500 is scheduled to start in the first half of 2024.

In addition, Vir Biotechnology, Inc. announced the initiation of a Phase I trial for its innovative HIV vaccine candidate, VIR-1388. Engineered to instruct the immune system to generate T cells capable of recognizing HIV and triggering an immune response to thwart the establishment of chronic infection, VIR-1388 represents a promising avenue in HIV prevention.

Supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the Bill & Melinda Gates Foundation, the Phase I trial is underway to assess the safety, reactogenicity and immunogenicity of VIR-1388. The company anticipates releasing initial data from the Phase I trial in the second half of 2024.

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