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Monday Article #63: HIV/AIDS and The Sustainable Development Goals 3

Improving the health and wellbeing of the world's people is at the core of the Sustainable Development Goals (SDGs), reflected in targets that call for ending the epidemics of AIDS, tuberculosis, and malaria; achieving enormous improvements in maternal and child health; and tackling the growing burden of non-communicable diseases (NCDs). [1]


HIV (human immunodeficiency virus) is a virus that attacks cells that help the body fight infection, making a person more vulnerable to other infections and diseases. It is spread by contact with certain bodily fluids of a person with HIV, most commonly during unprotected sex (sex without a condom or HIV medicine to prevent or treat HIV), or through sharing injection drug equipment. [2]

On the other hand, AIDS is the late stage of HIV infection that occurs when the body’s immune system is badly damaged because of the virus. A person with HIV is considered to have progressed to AIDS when the number of their CD4 cells falls below 200 cells per cubic millimeter of blood (200 cells/mm3). (In someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm3.) or they develop one or more opportunistic regardless of their CD4 count. [2]


HIV-1 is the human retrovirus responsible for the HIV/AIDS pandemic, which has claimed more than 30 million lives over the past four decades. HIV infection continues to be a major global public health issue, with currently around 40 million people living with HIV (PLWH). As a retrovirus, HIV can be described as a genomic pathogen. Indeed, it not only uses the molecular machinery of the infected cell for replication and dissemination but it also has the remarkable capacity to integrate a DNA copy of its RNA genome into a host cell chromosome. By becoming part of the human genome, HIV can persist in long-term cellular reservoirs for decades, making it extremely challenging to develop therapeutic strategies resulting in complete eradication. [3]


HIV enters its main target cell, the CD4+ T lymphocyte, by binding to its receptor CD4 and to the co-receptor CC-chemokine receptor 5 (CCR5). This binding event triggers the fusion of the viral and human cell membranes, initiating a complex intracellular life cycle that will lead to the production of new viruses (Fig. 1). The natural immune response against HIV infection relies mostly on CD8+ T cells, also called cytotoxic T lymphocytes (CTLs). Upon primary infection, intense HIV replication results in a very high plasma viral load, measured as copies of the HIV RNA genome per millilitre of plasma, which is then partly controlled by the specific CD8+ T cell response. The very diverse human leucocyte antigen (HLA) class I molecules play a central role in this immune response by presenting small viral fragments, called epitopes, at the surface of infected cells. The recognition of these epitopes by CTL leads to the elimination of HIV-infected cells. A more efficient immune response is linked to a lower viral load during the chronic phase of an untreated infection and to slower disease progression, though it is unable to eliminate the virus. [4]


Fig. 1 Schematic representation of the HIV life cycle and the HLA-mediated host response


Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS. HIV host genomic research, which aims to understand how human genetic variation affects our response to HIV infection, has progressed from early candidate gene studies to recent multi-omic efforts, benefiting from spectacular advances in sequencing technology and data science. In addition to invading cells and co-opting the host machinery for replication, HIV also stably integrates into our own genome. The study of the complex interactions between the human and retroviral genomes has improved our understanding of pathogenic mechanisms and suggested novel preventive and therapeutic approaches against HIV infection. [3]


Effective treatment with HIV medicine (called antiretroviral therapy or ART). ART is recommended for everyone who has HIV, however ART cannot cure HIV but HIV medicines help people with HIV live longer, healthier lives. If taken as prescribed, HIV medicine can reduce the amount of HIV in the blood (also called the viral load) to a very low level. This is called viral suppression. Having less HIV in the body give the immune system a chance to recover and produce more CD4 cells. By reducing the amount of HIV in the body, HIV medicine also reduce the risk of HIV transmission. If a person’s viral load is so low that a standard lab can’t detect it, this is called having an undetectable viral load. People with HIV who take HIV medicine as prescribed and get and keep an undetectable viral load can live long and healthy lives and will not transmit HIV to their HIV-negative partners through sex. [5]


At this moment of uncertainty for the future of the HIV response and for global health generally, the International AIDS Society and The Lancet convened an international Commission of global experts and stakeholders to assess the future of the HIV response in the context of a more integrated approach to health. A central finding of the Commission is that the HIV epidemic is not on track to end and that existing tools are insufficient. Although antiretroviral therapy (ART) has transformed the HIV response by averting deaths, improving quality of life, and preventing new HIV infections, HIV treatment alone will not end the epidemic. The UNAIDS 90-90-90 approach must be accompanied by a similarly robust commitment to scaled-up primary HIV prevention and to the development of a preventive vaccine and a functional cure for HIV. Ironically, the diminishing energy on HIV is occurring at the moment when lessons learned during the HIV response could serve as pathfinders in the quest for sustainable health for all. [1]


References

[1] Anna Grimsrud, et al. (2018). Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission. Retrieved from NIH : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323648/


2] What Are HIV and AIDS? (2023). Retrieved from HIV gov: https://www.hiv.gov/hiv-basics/overview/about-hiv-and-aids/what-are-hiv-and-aids/


[3] Paul J. McLaren & Jacques Fellay. (2021, June 24 ). HIV-1 and human genetic variation . Retrieved from nature reviews genetics : https://www.nature.com/articles/s41576-021-00378-0


[4] Norman L Letvin & Bruce D Walker. (2003 , July 01 ). mmunopathogenesis and immunotherapy in AIDS virus infections. . Retrieved from nature medicine : https://www.nature.com/articles/nm0703-861


[5] HIV Treatment: The Basics . (n.d.). Retrieved from HIVinfo. NIH.gov: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-treatment-basics#:~:text=What%20is%20the%20treatment%20for,HIV%20treatment%20regimen)%20every%20day.


 

This article was prepared by Emeralda Erna Nordin

 

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