December 1 marks World AIDS Day, which aims at increasing awareness of the still crucial problem of HIV infection that currently affects approximately 38 million people worldwide.

We have interviewed Guido Poli, Full Professor of General Pathology at Vita-Salute San Raffaele University and Group Leader of the Human Immuno-Virology Unit at IRCCS San Raffaele Hospital, who has been studying HIV infection mechanisms and subsequent immune cell response for the last forty years.

Not only lymphocytes

HIV preferentially infects CD4-positive T lymphocytes, 95% of which become subsequently depleted. This leads to sever weakening of the immune system resulting almost inexorably in the Acquired Immunodeficiency Syndrome (AIDS), which predisposes the human body to a plethora of additional “opportunistic” infections and cancer. Within the remaining infected T lymphocytes, a fractions survives and maintain the virus integrated in their genome, but silent,m therefore invisible to immune recognition, thus making virtually impossible to fully eradicate HIV from the body. Luckily, with the current antiretroviral therapies it is possible to keep the infection under control and ensure a good quality of life for patients.

While much is known about the role of T-lymphocytes in maintaining memory of the infection, in the last ten-fifteen years research has been focusing also on the study of macrophage involvement in mediating HIV storage and latency.

“Macrophages are more resistant than T-lymphocytes in surviving the viral infection, which does not result in their depletion. However, macrophages themselves become incubators for latent viral particles accumulating in virus containing intracellular compartments. My group has contributed at investigating how immune as well as pharmacological factors contribute to regulating macrophage-mediated HIV storage”, says Professor Poli.

In the last years, Professor’s research has led to the development of an in vitro model to study how functional polarization of primary human macrophages to pro-inflammatory M1 contributes to HIV reversible quiescence.

“We have shown that, in an in vitro model of HIV infection, induction of M1 (proinflammatory)-polarization in primary human macrophages before and seven days after the infection results in significant, but reversible, containment of virus replication. This is accompanied by reduced total and integrated virus DNA, decreased expression of viral RNA and increased activation of restriction factors, such as APOBEC-3A, that macrophages use to fight and contain the virus. This is an interesting experimental model to study reversible viral quiescence in macrophages that opens future perspectives for possible treatments”, explains Poli. “Currently, we are leveraging the power of next-generation sequencing to further characterize the transcriptome of M1-polarized macrophages in the context of HIV latency”.

Prevention remains imperative to keep HIV under control

Despite the availability of antiretroviral drugs that ensure a long-life expectancy for patients, prevention remains the most important measure to keep HIV-infections under control at the general population level. Research on the development of a vaccine against HIV is still ongoing and there is no such option available at the moment.

“This is complicated by the fact that HIV changes constantly and quickly, resulting in many different viral variants. Additionally, HIV is very good at hiding from the immune system, which eventually comes too late- that is, when the viral genome has already integrated into the cell DNA. This further complicates any preventive treatment that involves immune cells, as it is the case with vaccination”, concludes Professor Poli.

Currently, the use of condoms during a sexual intercourse remains the most effective way to prevent HIV as well as other sexually transmitted infections. In addition, pre-exposure prophylaxis (PrEP) with the same antiretroviral agents used for therapy represents a further measure to prevent HIV-mediated infection before a sexual intercourse, although it does not protect from other STDs.