heroes who keep their distance

There are extraordinary individuals in the world who have defied one of the world’s deadliest viruses: HIV. These are the rare elite controllers, individuals who have kept the virus under control for decades naturally, without the need for antiretroviral drugs. Although these cases are extremely rare, science is striving to understand the mechanisms behind this innate ability and to apply this knowledge to the global fight against HIV.

A recent scientific review published in the journal Med by Cell Press examines the data on these elite controllers and points to new avenues of research toward a functional cure. Since HIV emerged in the 1980s, the virus has killed 40 million people and continues to cause 630,000 deaths globally each year. While there is no cure in sight, advances in science have made it possible to contain the virus with antiretroviral drugs, although the virus has not yet been eradicated.

Javier Martinez-Picado, the study’s author and an ICREA researcher in Irsicaixa, explains that without antiretroviral treatment, the immune system wages a battle against the virus that typically lasts eight to 12 years before AIDS manifests. However, elite controllers are an exception to this rule and keep the virus at bay without medication. This ability occurs in about one in every 300 patients, although in most cases the protection is temporary.

Martinez-Picado’s team has documented nine cases of exceptional elite controllers. The most resilient, reported in Australia in 2019, controlled the virus for 37 years. Other cases in Spain and Argentina have control periods ranging from eight to 30 years. Most of these patients are Caucasian women of childbearing age, although the researchers note that this may be due to greater accessibility and availability of biological samples in this demographic.

Key factors

The location where the virus integrates into the DNA and the initial immune system response are key factors in these cases. Martinez-Picado compares the situation to planting a seed: just as a seed grows better in fertile soil, a virus can replicate more effectively in active regions of DNA. However, if the virus inserts itself into inactive genetic regions, its ability to replicate is greatly reduced.

In addition, the immune systems of these elite drivers have unique characteristics. Some have mutations in the CCR5 gene, which makes it difficult for the virus to penetrate cells. Others have genetic variants associated with HLA, a part of the immune system that influences the cellular response to infections.

Viral reservoirs

Studies have also shown that these patients have much lower viral reservoirs than those taking antiretroviral drugs. These reservoirs contain defective viruses that cannot replicate. Ezequiel Ruiz-Mateos of the AIDS Research Group (Gesida) suggests that these people could be cured if the virus is present in their bodies but cannot replicate.

An intriguing aspect is the large number of Caucasian women among the exceptional controllers, which points to possible gender-related immune factors that have not yet been identified. Martinez-Picado speculates that women of childbearing age may have a more effective immune system to protect the fetus, which could explain their resistance to HIV.

Studying these elite controllers opens up new avenues of research, such as genetic modification to prevent CCR5 expression and strengthen the immune system. While many unknowns remain, these cases offer real hope for a future functional cure for HIV, demonstrating that near-complete viral suppression is possible in humans. @mundiario

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