Trends and Developments in HIV Research

Novel treatment strategies and advances in care have transformed the lives of people living with HIV (human immunodeficiency virus). Antiretroviral therapy (ART), once-daily single-tablet regimens (STRs), and PrEP (pre-exposure prophylaxis) are some major milestones that have changed the trajectory of the deadly disease.

The change has been disruptive, but HIV continues to remain a global public issue. Worldwide, around 38 million people are living with HIV and there is an unmet need for more effective drug candidates and strategies for treatment as well as prevention of new infections. 

This article covers some recent developments in the management of HIV. 

The Advent of Long-Acting Therapies 

Long-acting therapies are set to make a huge difference in the lives of people living with HIV. These therapies don’t need to be taken daily and can be dosed weekly or monthly - a feature that may improve patient convenience and improve treatment adherence by eliminating the daily reminder of treatment. 

Long-acting therapies can be specifically useful in the pediatric populations with HIV, a group with huge unmet needs. By reducing the frequency of treatment administration in children, long-acting therapies can improve quality of life and adherence to regimens.

ViiV Healthcare’s CABENUVA, approved by the FDA in January 2021, is the first long-acting injectable HIV treatment in the market. The therapy consisting of one cabotegravir injection and one rilpivirine injection needs to be administered just once a month. FDA also approved VOCABRIA (cabotegravir) 30 mg tablets which should be taken in combination with oral rilpivirine (EDURANT) for one month before starting treatment with CABENUVA to ensure the medications are well-tolerated before switching to the extended-release injectable formulation.

In December 2021, FDA approved ViiV’s Apretude (cabotegravir extended-release injectable suspension) for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV. Apretude is given first as two initiation injections administered one month apart, and then every two months thereafter.

Apart from ViiV Healthcare, Gilead is expected to complete regulatory filings this year for their long-acting self-injectable HIV treatment lenacapavir. Lenacapavir must be injected once every six months. If approved, the HIV-1 capsid inhibitor will be the first approved treatment of its kind. Lenacapavir (in combination with other treatments) is being developed for heavily treated patients who have become resistant to multiple drugs, a particularly difficult-to-treat group of patients.

HIV Vaccines – A Promising Strategy to Fight HIV

An effective HIV vaccine can help combat HIV and is seen as a potential strategy to curb this deadly disease. Mosaic-based vaccines and messenger RNA (mRNA) vaccines are some novel technologies being evaluated.

Mosaic-based vaccines consist of mosaic immunogens, such as a mosaic glycoprotein 140 (gp140). These immunogens, which are delivered through viral vectors, have the capacity to induce a broad immune response as they are made up of pieces of different HIV strains. 

In September 2021, Janssen’s mosaic-based HIV vaccine candidate failed to offer substantial protection against the disease in the Phase IIb Imbokodo clinical trial in women in sub-Saharan Africa. The company decided to discontinue the Imbokodo study. 

The Imbokodo study is discontinued, but Janssen is continuing the Phase 3 Mosaico study. The Mosaico study is testing the safety and efficacy of a different composition of the HIV vaccine regimen among men who have sex with men (MSM) and transgender individuals. The trial is being conducted in the Americas and Europe where different strains of HIV are circulating.

The success with mRNA vaccines for COVID-19 has generated hopes that mRNA techniques can also be used in HIV. Many research groups including the International AIDS Vaccine Initiative (IAVI) are working towards this mission. Moderna, the company which developed the COVID-19 mRNA vaccine is set to test its vaccine candidate mRNA-1644 for HIV. mRNA-1644 is based on the same mRNA platform as the COVID-19 vaccine.

Apart from mRNA vaccines, researchers are also considering replicating viral vector-based (Vesticular Stomatitis Virus) vaccine comprising a recombinant VSV vector that incorporates an HIV envelope gene.

A vaccine can do wonders, but the development of an HIV vaccine is easier said than done. HIV is a highly variable virus and can easily target immune cells and integrate into the host genome causing infection as well as latent infection. Another factor is the lack of evidence for what exactly constitutes an appropriate immune response to HIV.

A Cure for HIV - How Close are We?

A cure for HIV may be the final phase of HIV control but developing a cure is challenging. HIV has the ability to hide itself and lay dormant in pockets of host T cells. These pockets, known as “latent viral reservoirs”, can be found in peripheral blood, lymph nodes, gut-associated lymphoid tissue, T lymphocytes, and the central nervous system. 

Latent viral reservoirs are unrecognized as harboring HIV by the immune system and can remerge if ART is stopped after achieving successful HIV suppression. Additionally, these viral reservoirs can persist despite years of treatment with anti-HIV drugs. 

Elimination of the viral reservoirs is key to HIV cure, but evidence suggests that more than 70 years of continuous, fully suppressive HIV treatment is required to completely eliminate the HIV reservoir. Another option is the induction of HIV from its latent state, which would decrease reservoir load and reduce the time to eradication. Several concepts have been explored to combat latency and a few are described below:

· Shock-and-kill approaches – This involves the administration of latency reversal agents, which reactivate latent HIV hiding in immune cells. The next step is the elimination of the reactivated cells using the body's immune system (host immune clearance and HIV-cytolysis) or anti-HIV drugs.

· Induction of deep latency – In this approach, the HIV reservoirs are deeply silenced to induce the proviral HIV so that HIV would not rebound, or the rebound is significantly delayed even when treatment is stopped.

· Precise excision of integrated proviruses via CRISPR-Cas9 or other precision nuclease technologies

ViiV Healthcare, Gilead Sciences, and Excision Biotherapeutics are some companies working towards developing a cure for HIV.   

HIV therapies - Developments in China

HIV remains a major problem in China, with AIDS-related mortality rising sharply in recent years. The HIV market landscape in China is largely dominated by global companies like hospital supply companies, but due to the huge potential for HIV treatment in China, many local companies have joined the race.

In 2018, the first Chinese proprietary HIV therapy injectable Ai Ke Ning (albuvirtide) was approved. Albuvirtide is a long-acting fusion inhibitor developed by Frontier Biotechnologies. The drug is to be administered by a once-weekly injection.

National Medical Products Administration (NMPA) has approved the Abbreviated New Drug Application (ANDA) for the generic version of Truvada (emtricitabine/tenofovir). The generic made by Chai Tai-Tianqing Pharmaceutical will be the first Chinese-made HIV combination tablet in the country.  

In June 2021, China’s Jiangsu Aidea Pharmaceuticals received marketing approval from Chinese health authorities for Ainuovirine (ACC007), a new -nucleoside reverse transcriptase inhibitor (NNRTI). As the first oral HIV treatment in China, Ainuovirine is expected to take a huge market share.

In July 2021, NMPA gave conditional approval to Henan Sincere Biotech Co. Ltd.’s dual-targeting, oral HIV drug, azvudine, to treat HIV-1-infected adult patients with high viral loads. 

Ascletis is developing ASC09F, a combination tablet containing ritonavir and ASC09, a protease inhibitor. In 2020, Ascletis received investigational new drug (IND) approval for ASC09F. A phase I pharmacokinetic trial has been completed in China for the drug.

The Need for Continuous Research

By transforming care, innovations can change the trajectory of the HIV epidemic and improve patient outcomes. Identifying knowledge gaps and priority areas as well as including knowledge from fields such as COVID-19 can facilitate progress in HIV research.

About the Author

Neeta Ratanghayra

Freelance Medical Writer

Neeta Ratanghayra is a freelance medical writer, who creates quality medical content for Pharma and healthcare industries. A Master’s degree in Pharmacy and a strong passion for writing made her venture into the world of medical writing. She believes that effective content forms the media through which innovations and developments in pharma/healthcare can be communicated to the world.

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