Clues to HIV Persistence on ART

HIV has a built-in backup plan when it comes to its survival. While scientific technology has progressed to the point where antiretroviral drugs can effectively kill HIV viruses in the body that are out in the open, HIV persists in places where the drugs can't get to them. These places are called HIV reservoirs, and these reservoirs ensure that small batches of virus remain in the body, ready to replicate when necessary. This is part of what makes HIV a chronic infection—the remaining virus finds ways to remain dormant in the body until activated. Research is now focusing on cracking the case of HIV persistence.

The goal of researchers now is to remove the "chronic" term from the chronic illness that is HIV and come up with a cure for the disease. A better understanding of HIV and how it infects people to begin with might be the key to discovering ways to enter the reservoirs within the body and eliminate the virus. As we already know, HIV infects cells in two ways: through blood plasma contact with T-cells, and from infected T-cells to non-infected T-cells.  Antiretroviral drugs, while effective, don't remove the entire virus quantity, and all it takes is for one HIV virus to remain behind for the replication to continue.

Recent research has found that while antiretroviral therapy (ART) is effective at significantly reducing the number of plasma-to-T-cell transmissions of HIV, it's not as effective against T-cell-to-T-cell. The remaining virus hides in infected T-cells, which allows it to easily be passed on to non-infected ones; this, in fact, is one of the reasons why HIV persists through ART. To use a football analogy, ART is able to intercept passes through the air (plasma) from one cell to another, but it can't stop direct handoffs. A strategy is needed to defend against each separately, because the same defense can't be used against both.

Even with antiretroviral drugs present, infected T-cells can still infect other T-cells in close quarters instead of through the bloodstream; this often happens in the lymph nodes. Therefore, in order to find an actual cure for HIV, researchers need to find a way to deal with HIV reservoirs filled with both latent HIV virus and active virus that is transmitted from cell-to-cell. The clues to HIV persistence are clear, but this is one of those situations where the answer seems obvious but the path toward deriving the answer is extremely difficult.

Contact:
Alain Lafeuillade
AVPS
1208 avenue Colonel Picot
Toulon 83100 France
33-4-94616340