StemCell Therapy

The human immunodeficiency virus (HIV) has remained a significant challenge for researchers as there is currently a lack of cure or vaccine for this disorder.

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While antiretrovirals have improved the types of therapy available for patients, the ineffective requirement of lifetime treatment, as well as the development of resistance, is a major hurdle. However, the emergence and growth of nanotechnology may be a promising solution for a higher level of effective treatment as well as prevention of both HIV and acquired immunodeficiency syndrome (AIDS).

HIV was first identified in 1983 as the causative agent that resulted in AIDS, which was first reported in 1981.

The progression of the virus and the associated disease has been reported to be a global pandemic as one of the global lead causes of mortality in adults. The World Health Organization (WHO) has estimated the number of people living with HIV in 2020 was approximately 37.7 million; this can be translated as 0.7% of the global population, with Africa comprising the highest prevalence compared to other continents.

This majorly infectious disease consists of a primary strain, HIV-1, that can be traced to the chimpanzee species. This virus is an enveloped retrovirus that consists of two copies of single-stranded RNA.

There are three distinct stages of HIV, which describe the progression of the virus, including acute HIV infection, chronic HIV infection, and AIDS.

These can be summarized as the multiplying of the HIV virus, including the initial rapid destruction of CD4 T lymphocytes within the host, causing flu-like symptoms. This can then progress into the second asymptomatic stage, where the virus continues to multiply at low levels; within this chronic stage, the infection can progress into AIDS in 10 years or longer without antiretroviral therapy.

The final stage of HIV consists of AIDS, which is the most severe stage of the infection and can be characterized as having a high level of damage to the immune system, where the body is unable to fight against opportunistic infections. A diagnosis of AIDS is made when HIV patients have a CD4 count of 200 cells/mm3.

HIV/AIDS treatments have focused on antiretroviral therapies, with early treatment being only effective to a certain extent; the first drug that was FDA approved was in 1987, and since, approximately 25 drugs have received approval.

The progression of research, which included the release of protease inhibitors as well as the emergence of triple-drug therapy within the mid-1990s was highly promising for the efficacy of HIV/AIDS treatment. Currently, the highest standard of HIV/AIDS treatment consists of highly active antiretroviral therapy, involving three or more drugs provided simultaneously.

With further research into disease prevention strategies, vaccines have been considered the most effective agent for fighting global infections, evidenced by efficient control over infectious diseases such as measles, mumps, and rubella.

The challenges that can be associated with this chronic disease consist of requiring patient compliance for lifetime treatment, which can be difficult to adhere to. A lack of adherence to treatment can increase the probability of treatment failure and increase the likelihood of developing resistant strains of the virus.

Another limitation includes poor aqueous drug solubility, as this can impact the availability of the drug within the body and result in ineffective treatment of HIV.

The advancement in nanotechnology and nanomedicine has provided a promising future for HIV/AIDS therapeutics.

With the advancement of nanomedicine, strategies have been explored to overcome current challenges associated with HIV treatment. This includes oral administration of antiretroviral drugs and improving the water solubility of drugs, such as through solid drug nanoparticles (SDN).

Research into SDN formulations has been produced through a freeze-drying approach, which has been predicted to provide a similar pharmacokinetic standard as a conventional anti-HIV drug. However, this nanomedicine formulation was theorized to allow patients to take a 50% lower dose while experiencing the same effect. This prediction was validated with in vivo experimentation.

The development of SDN formulations has enabled success in superseding conventional oral drug formulations, such asritonavir-boosted lopinavir, which utilizes 42% ethanol and 15% propylene glycol. The use of lopinavir SDN formulations can achieve the production of an effective oral drug without the inclusion of ethanol.

Additionally, the potential inclusion of nanomedicine within this field of therapeutics allows for low-cost production of effective drugs as well as a decrease in required doses for patients.

Other subsets of nanomedicine that can be used for HIV therapeutics include long-acting injectable formulations (LAI), which can provide a solution to patient issues associated with low adherence to lifetime treatments.

An example of a drug that has been re-formulated to carry a nanomedicine component includes the non-nucleoside reverse transcriptase inhibitor, rilpivirine, which has been available as an oral medication from 2011, before being nanoformulated as a LAI.

This LAI nanomedicine has been proven to be effective, with concentrations being detected in rats up to 2 months after subcutaneous and intramuscular administration as well as detected in dogs for up to 6 months after administration.

New research in this area has included the Herbert Wertheim College of Medicine(HWCOM), who have undertaken nanotechnology research into the delivery of anti-HIV drugs across the blood-brain barrier, aiding in targeting HIV reservoirs within the brain. This research has included the development of a revolutionary technique consisting of using tiny magneto-electric nanoparticles as drug carriers.

Nagesh Kolishetti, one of the studys corresponding authors, stated, This delivery system can reduce the viral load, the amount of virus present, which normally contributes to neurological problems.

This type of combination therapy with the nanoparticles could result in a highly effective treatment regimen for the HIV-infected population who are addicted to a substance of abuse.

This is significant as HIV can cause neurological problems and disorders such as dementia and memory loss, which can be further increased by substance abuse

The future of HIV therapeutics can be said to be greatly intertwined with nanomedicine, with research into the use of nanoformulations that attempt to overcome the challenges of current HIV treatments.

With reports from WHO stating that 73% of HIV patients are treated with antiretroviral therapy and 680,000 deaths in 2020, this field requires a revolutionary change to traditional medicine to provide better treatment and even preventative care for this chronic disease.

Curley, P., Liptrott, N. and Owen, A., 2018. Advances in nanomedicine drug delivery applications for HIV therapy.Future Science OA, 4(1), p.FSO230. Available at: 10.4155/fsoa-2017-0069

FIU News. 2022.Researchers advance the use of nanoparticles to deliver HIV/AIDS drugs to the brain. [online] Available at: https://news.fiu.edu/2021/fiu-researchers-advance-the-use-of-nanoparticles-to-deliver-hivaids-drugs-to-the-brain

Hivinfo.nih.gov. 2022.The Stages of HIV Infection | NIH. [online] Available at:https://hivinfo.nih.gov/understanding-hiv/fact-sheets/stages-hiv-infection

Mamo, T., Moseman, E., Kolishetti, N., Salvador-Morales, C., Shi, J., Kuritzkes, D., Langer, R., Andrian, U. and Farokhzad, O., 2010. Emerging nanotechnology approaches for HIV/AIDS treatment and prevention.Nanomedicine, 5(2), pp.269-285. Available at: 10.2217/nnm.10.1

Worldpopulationreview.com. 2022.HIV Rates by Country 2022. [online] Available at: https://worldpopulationreview.com/country-rankings/hiv-rates-by-country

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Nanomedicine and HIV Therapeutics - AZoNano

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