Genetic Modulation Therapy Through Stem Cell Transplantation for Human Immunodeficiency Virus 1 Infection

Varshil Mehta,Shivika Agarwal,Divya Chandramohan

doi:10.7759/cureus.1093

Abstract

Highly active anti-retroviral treatment has changed the dimensions of the outcomes for patients suffering from human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). However, HIV infection is still an ailment which is spreading throughout the world extensively. Given the confinements of the present restorative methodologies and the non-availability of any strategic vaccination against HIV, there is a squeezing need to build a therapeutic treatment.Viral tropism for HIV includes CD4+ cells, macrophages, and microglial cells, and it is through binding with co-receptors C-C chemokine receptor type 5 (CCR5) and C-X-C chemokine receptor type 4 (CXCR4). While these cell types are present in all individuals, there are rare cases that stayed uninfected even after getting exposed to an overwhelming load of HIV. Research revealed a homozygous 32-base pair deletion (Δ32/Δ32) in CCR5. After careful consideration, a hypothesis was proposed a few years back that a cure for HIV disease is possible, through hematopoietic stem cells transplantation from a donor homozygous for the CCR5-Δ32 deletion.Hematopoietic stem cell (HSC) based quality treatment may serve as a promising tool as these perpetual, self-renewing progenitor cells could be modified to oppose HIV infection. If done properly, the changed HSCs would offer the permanent creation of genetically modified cells that are resistant to HIV infection and/or have improved hostility to viral action which will eventually clear the contaminated cells.The purpose of this review is to concentrate on two facets of HSC genetic treatment for potentially life-threatening HIV infection: building HIV-resistant cells and designing cells that can target HIV disease. These two strategic approaches can be the frontline of a quality treatment plan against HIV infection and, as an individual treatment or a combination thereof, has been proposed to possibly destroy HIV altogether.

Highlights

BackgroundAs indicated by the Joint United Nations Programme on Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (UNAIDS), there were roughly 36.7 millionHow to cite this article Mehta V, Chandramohan D, Agarwal S (March 13, 2017) Genetic Modulation Therapy Through Stem Cell Transplantation for Human Immunodeficiency Virus 1 Infection
An alarming 2.1 million people were recently contaminated with human immunodeficiency virus (HIV) in 2015
The greater part of these children live in subSaharan Africa and were contaminated by their HIV-positive mothers amidst pregnancy, labor, or breastfeeding [1]

Summary

Introduction

As indicated by the Joint United Nations Programme on Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (UNAIDS), there were roughly 36.7 million. Proper thymic selection of the modified cells and exclusion of endogenous TCR surface expression will be allowed by molecularly cloned TCR, eliminating the chances of generating self-reactive TCR through mispairing [43] This therapy would allow a long-lived and renewable immunity system to continuously produce antiviral cells that could lead to HIV eradication. The cloned TCR, which matches the patient’s human leukocyte antigen (HLA) type and viral genome, could be used to genetically modify patient’s HSCs which can subsequently allow the development of evolved and sustained modified CD8+ T-cells capable of targeting and eradicating HIV-infected cells. With further enhancement of technology related to the modulation of stem cells, it is expected that the adverse effects and potential risk will diminish [50]

Conclusions

Disclosures

Deeks SG

Findings

10. Piche A: Gene therapy for HIV infections