Reacción a "A study suggests that women's immune systems are better at controlling HIV"

A well-known but little-studied observation is the greater resistance of the female biological sex to certain infections. In the specific case of HIV, women represent 10-15% of people with HIV in our environment. However, when we identify those exceptional patients who control HIV infection in the absence of treatment, 60% of these “elite controllers” are women. This resistance phenotype is attributed to a better immune response due to the greater expression of genes involved in the potency of the immune system that are located on the X chromosome, meaning that women have higher levels of certain proteins with antiviral mechanisms of action. Despite this advantage—resistance to infection—the downside of a more active immune system is the development of autoimmune diseases, which are also much more common in females.

On the other hand, HIV persists in the body because it forms reservoirs that are inaccessible to antiretroviral treatment, making HIV a chronic infection that requires lifelong treatment. The unanswered question is: how does this better immune response affect HIV reservoirs? And, consequently: if these reservoirs are under immune control, would it be possible to suppress antiretroviral treatment?

The article by Tan et al. analyses this question using advanced technology that allows us to define the reservoir based on two parameters:

1. Whether it consists of intact or defective viruses.
2. Whether the intact viruses, which are the dangerous ones, can actively multiply or are located in the so-called “non-genic regions” of our DNA, which are “dead ends”, dead spots where there is no gene expression.

Previous results suggested that after more than 15 years of treatment, the reservoir consists of defective viruses and intact viruses integrated into “dead” or “inactive” regions of the human genome. This article describes that this profile occurs more in women than in men.

1. Women have less variable integrated viruses, reflecting less replication.
2. Intact viruses are integrated into repressed areas of human DNA.
3. This more controlled reservoir is associated with immune activity mediated by cells called Natural Killer (NK) cells.

In contrast, in men there is greater viral diversity, more intact viruses integrated into “dangerous” areas and a different immune response mediated by cytotoxic T lymphocytes, against which the virus can more easily generate resistant variants.

In summary, this is an important article that provides a better understanding of an open question and, if confirmed and further explored, has potential therapeutic implications, as it would allow us to define reservoir profiles for discontinuing antiretroviral treatment. The data would also support immunomodulatory treatments that enhance NK activity to achieve this favourable immune response that allows HIV control.

The article opens up a line of research that raises new questions and has limitations: it is a cross-sectional study whose data must be confirmed in longitudinal studies. The study is conducted on peripheral blood lymphocytes, but the large reservoir of the virus is in the central lymphoid organs (lymph nodes and intestinal tissue) and, finally, it involves a population of elderly women. Would it be the same in a context of adolescents? And what is the influence of hormonal status on this resilient immune response?

As a final comment, the article places women at the centre of HIV research, an important gap since most studies do not consider biological sex as an independent variable of analysis. It is important to remember that, although in our environment 85% of people with HIV are men, in sub-Saharan African countries the proportion of women with HIV is 50%. It therefore represents a step forward in gender-neutral research.