Why We Haven’t Cured HIV Infection: A Major Hurdle To Overcome

A little more than twenty years ago, two developments occurred around the same time that tremendously advanced our ability to treat and manage HIV infection. First, we finally had powerful combinations of drugs that could suppress the HIV virus, primarily a class known as the protease inhibitors (drugs like Viracept, Kaletra, Reyataz and Prezista). Around the same time, we had validated that the viral load, a test that tells how much HIV was in the blood, was a good way to measure how active the infection was and how effectively the drugs were working. Combining these two advancements, we were able to show that these powerful drug combinations could totally suppress the activity of the virus in the blood undetectable viral load.

This was fantastic because with an undetectable viral load from these drug combinations the immune system would improve and would be protected. So, if there is no more virus detected in the blood, that person is cured right? That’s what we were hoping. Unfortunately, whenever we would stop treatment in someone who had been undetectable, the virus would soon reappear in the blood! How could it be undetectable and then suddenly reappear after stopping the medicine? Where was this virus coming from, if the person had been undetectable??

As you know, the HIV virus targets the CD4+ cell, a type of T-lymphocyte. The T-lymphocytes are the special infection-fighting white blood cells. Normally, HIV virus infects cells, turns them into a factory to make more viruses and then, the new viruses are released to spread the infection. The infected lymphocytes die, which is why the immune system becomes damaged as more of the protective cells are killed off by the virus. But something else interesting happens.

Some of the infected lymphocytes don’t die. After infection, these cells start to quiet down and then become dormant. They are not active and it’s almost as if they are hibernating. The HIV virus is unable to replicate when the cells are in this dormant state. Also, because the virus can’t replicate, the medicines that suppress HIV aren’t able to work well in these particular lymphocytes. The ability of these lymphocytes to go into a dormant state is an important feature of the immune system.