With each passing day, we’re learning something new about the sneaky nature of the human immunodeficiency virus. Studies are delivering valuable information on how it works and what makes it so evasive.
One of the latest research publications demonstrates the manner in which HIV can “hide” from antiretroviral therapy. The study suggests that the virus can create hidden reservoirs within the body as early as the first days of infection, allowing it to escape from the detrimental effects of medications.
What Happens During the First Weeks of an HIV Infection
Published in the Immunity journal, the study was launched over 10 years ago. It enrolled over 800 volunteers to track what was going on during the acute stage of the HIV infection.
According to the researchers, a small fraction of the virus can integrate into the genome of the CD4 T cells that it targets. This happens during the very first days of an active infection. While completing the process, the virus refrains from replicating. This way, HIV remains concealed and cannot be detected by the earliest tests that are used to figure out if active viral replication is taking place.
These hidden reservoirs (latent reservoirs are they are scientifically known) also remain undetected by the immune system. As a result, HIV can lie dormant within the immune cells, eventually beginning rapid replication in the absence of antiretroviral medications.
The findings of the new study are quite impressive and a bit alarming at the same time.
Less than seven days into an active infection, the number of affected CD4 T cells goes up from 10 to 1,000 per million. It’s also interesting to point out that the kinds of cells targeted during the acute phase is different from those that HIV attaches to later on.
During the acute infection, HIV doesn’t affect many T follicular helper cells. These cells are very important for the replication of the virus and they become a primary target after the infection becomes chronic. That happens approximately two months after HIV is passed from one person to another.
Previously, researches believed that the T follicular helper cells were the first ones to be infected. Also, they’d been relying entirely on animal studies and models to draw such conclusions. The new clinical trial is of paramount importance as it highlights a viral spread mechanism that the scientific community didn’t know anything about until now.
Escaping Antiretroviral Therapy
Antiretroviral therapy is based on highly effective medicines that prevent the replication of the human immunodeficiency virus.
In the acute stage of an infection, however, this kind of therapy may be somewhat ineffective. The mechanism highlighted in the study quoted above suggests some of the ways in which HIV could neutralise antiretroviral medications (at least in the early stages of an active infection).
Starting antiretroviral therapy as soon as possible is still the general recommendations. Preventing the replication of the virus allows a person to maintain a healthy immune function and keep their status from changing.
According to researchers, however, new recommendations could be made to increase the effectiveness of early therapy even further.
For best results, it would be good to combine antiretroviral medications with another pharmaceutical that could get the virus out of its “hiding places” and reservoirs within the cells.
At the time of diagnosis, latent reservoirs are already established. It’s now up to the scientific community to determine whether treatment commenced during the acute phases of the infection could prevent the formation of such reservoirs.
Possibilities for New Cure Development
For years, researchers have been working on strategies aimed at activating latent viral reservoirs, making them visible to the immune system. When this happens, antiretrovirals can do their magic and wipe the immune system clear from these infected cells.
Some speculate that immunotherapy and latency-reversing agents used to quickly map out the virus can have a negative effect in the long run because they will eventually produce reservoirs with deeper latency than the ones already in existence.
According to the primary argument that the study authors make, the mechanism that the bodies of elite controllers employ is the one that needs to be studied and replicated in clinical settings.
Elite controller are people who can naturally supress and control the virus. They don’t need antiretroviral therapy to maintain a very low viral load. This happens because the HIV DNA is locked up in the parts of cellular chromosomes known as gene deserts. Gene deserts prevent the creation of new viruses, which allows elite controllers to achieve remission from an active HIV-infection without needing medications.
It may be possible for people to sequester the virus to gene deserts after undergoing an antiretroviral treatment for prolonged periods of time. This is a new hypothesis and it will potentially be tested out in new studies in the years to come.