40 years of AIDS: the pending challenges

June 5, 2021 marked the 40th anniversary of the first clinical description of cases of what was later called Acquired Immune Deficiency Syndrome (AIDS). The cases appeared published in the American Epidemiological Bulletin Morbidity Mortality Weekly Report (MMWR) in 1981. They were five previously healthy men who presented opportunistic infections in the context of a very serious cellular immunosuppression.

Just 2 years later, in 1983, the Laboratories of the Pasteur Institute in Paris isolated the infectious agent responsible for this new disease, the Human Immunodeficiency Virus (HIV).

Throughout these four decades it is estimated that nearly 40 million people have died of AIDS worldwide. What's more, some 38 million live with HIV, about a million people are still infected annually and about 700,000 die per year. In Spain the number of HIV patients rises to 150,000, and around 3,000 new infections arise per year.

The devastating pandemic

The first decade of the HIV pandemic was terrible from all points of view, with extremely high morbidity and mortality. So much so that this period is also known as the 'Middle Ages' of HIV.

There was general confusion, and the despair in patients and health personnel was enormous. This was contributed to by the fact that, although HIV had been identified in 1983, until 1986 in Spain HIV screening tests were not mandatory for all blood products (transfusions, etc.). On the other hand, during the early years it was not clear whether to attribute the cause of AIDS to a biological agent or to a chemical agent. To make matters worse, all attempts to obtain treatment for HIV had very modest success and very limited time.

In that first decade, HIV infection became the leading cause of death in our environment in people between 20 and 40 years of age. The radical change came in the second decade, after the 1996 International AIDS Congress in Vancouver (Canada). It was then that very powerful antiretroviral strategies appeared, capable of inhibiting the replication of HIV almost 100%, which caused mortality to decrease dramatically.

However, the adverse effects of the medication and the multiple daily pills that patients had to take were a very big obstacle to chronic treatment.

On the other hand, multiple treatment strategies included three-molecule therapies that, although highly effective, were accompanied by significant adverse effects such as lipodystrophy that limited the quality of life of patients, increasing the stigma of the disease.

One pill a day ... or a week

In the third decade of the pandemic, more powerful options than the previous ones finally appeared with an excellent safety profile (practically no adverse effects), of multiple families of drugs and combined in a single pill a day.

Since then, advances have been aimed at finding new molecules with an excellent efficacy, tolerance and convenience profile, which even allow parenteral administration (intramuscular or subcutaneous). This opens up the possibility of antiretroviral treatments administered every several weeks or months.

In addition, the foundations have been established for the effective control of the pandemic through prophylactic measures. This includes the early detection and treatment of those infected (test and treat, "Diagnose and treat"). But also pre-exposure prophylaxis (PrEP), consisting of administering antiretroviral molecules to people with a high probability of becoming infected in order to effectively avoid said infection. In addition, there is an insistence on investigating true prophylactic vaccines that can prevent HIV infection.

Complete cure and vaccinations

At present, HIV research faces two major challenges:

  1. To achieve its cure through new treatment strategies that allow to eliminate the virus in the infected patient.
  2. Get a preventive vaccine against HIV.

The Hospital Clinic itself is currently developing a prototype of a preventive vaccine based on the trimeric envelope of acutely infected viruses that, after the results obtained in laboratory and animal models, will begin its clinical development throughout this year.

Likewise, there are currently at least two other preventive vaccine projects in different phases of clinical research: Scripps-IAVI (vaccine project that is in phase I) and Janssen (mosaic vaccine against HIV that is in phase III).

In this context, it is important to highlight UNAIDS campaign to control the HIV epidemic. Its objective is none other than to diagnose by 2030 at least 95% of people infected with HIV, that 95% of them receive continuous therapy, and that 95% of those treated reach an undetectable plasma viral load of HIV. It is what is known as the 95-95-95 program.

The thing is not there. The campaign has also proposed that society as a whole totally eliminate the stigma associated with HIV infection.

Only the joint effort of infected people, community organizations, researchers, health personnel and institutions will allow us to effectively control what has been and is the worst social and health crisis of the second half in a matter of a few years. of the twentieth century, the infection by the AIDS virus.

This article was originally published on The Conversation for Jose Mallolas Masferrer, Head of the HIV-AIDS Unit of the Hospital Clínic-Barcelona. You can read it here.


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