One of the reasons why HIV cannot be eradicated in most cases and thus cure the infection lies in the sanctuaries or reservoirs of the virus, hiding places where HIV remains dormant but, at the same time, active. Until now it was thought that these reservoirs formed over time, but a study published in “Immunity” reveals that this is not the case. For the first time in humans, it has been shown that it is in the first days of infection that HIV can create these reservoirs where it will hide and persist during treatment.
In a study led by Nicolas Chomont of the University of Montreal (Canada), researchers found that a small fraction of the virus integrates into the genome of CD4+ T cells in the first weeks of infection (the acute phase), but it is not replicated there. Thus, it escapes the attention of the fastest diagnostic tool to date, which detects active viral replication. CD4+ T cells are the primary targets of HIV. They are white blood cells responsible for activating the human body’s defenses against infections.
“With the help of an analysis technique developed in our laboratory, we were able to observe and count virus-infected T cells in human samples collected in the early stages of infection,” explains Chomont, lead author of the study. “We were able to detect the presence of the virus through sequencing even when it was hidden in cells that were not involved in viral replication.”
To study these early phases of virus spread, researchers had access to blood and inguinal lymph node tissue samples from 25 people in the first acutely infected cohort of the US Armed Forces HIV Research Program. .
This cohort began more than 10 years ago in collaboration with the Thai Red Cross AIDS Research Center and has enrolled nearly 800 volunteers.
Through their analysis technique, the scientists were able to count virus-infected CD4+ T cells during the acute phase of infection.
These infected cells increased from 10 to 1,000 per million CD4+ T cells in less than seven days, demonstrating the extreme speed with which HIV spreads.
This is the first time that the early stages of infection in humans have been described with such precision.
They also found that the characteristics of HIV target cells in the first weeks of infection varied rapidly and differed depending on whether they were located in the blood or in the lymph nodes.
“For example, we noticed that few Tfh (follicular helper T cells) are infected by the virus during the acute phase of infection,” Chomont explains. Because they play a crucial role in viral replication, the scientific community thought they were the first to get infected.”
Until now, these types of studies have been carried out in animal models. Therefore, this is the first time that the early stages of infection in humans have been described with such precision.
Much of the world’s research devoted to eHIV study focuses on how to reactivate the virus that remains latent in the reservoirs to neutralize it.
“The sooner we start antiretroviral therapy, the more we will prevent the virus from replicating and the more we will limit the size of the reservoirs. We demonstrated it in 2020,” says Chomont.
However, it seems clear that early antiretroviral therapy must be combined with other treatment to force the virus out of hiding, he says, “because by the time of diagnosis latent reservoirs will already have been established in people infected with HIV.”
In collaboration with US scientists, this team is currently evaluating whether this type of treatment administered in the phase of acute infection would prevent the establishment of viral reservoirs.
