HIV Latency 101
It has been pointed out to me that if I am going to spend time talking about HIV latency, it might benefit my readers to understand what is meant by that. And to understand that, you need a basic understanding of the disease. So here it is, your crash courseon the course of HIV infection and viral latency.
Untreated HIV infection can be split into roughly three phases:
- Initial Infection and Acute Symptoms: This phase represents the 1-2 months immediately after infection. The virus integrates into your cells and provokes an immune response. This leads to flu-like symptoms that do not persist.
- Asymptomatic Phase: During this phase, which can last ~2-10 years, you have a relatively low viral load and demonstrate no symptoms. This is because the immune system is still in control. The virus is not causing CD4 T-cell death at an unmanageable rate and this phase persists until an immune escape event occurs.
- AIDS: Once the virus dodges immune control, it proliferates rapidly, killing CD4 T-cells and opening the body up to the spectrum of opportunistic infections that will ultimately lead to death.
HAART (Highly Active Anti-Retroviral Therapy) can essentially prolong the asymptomatic phase of the infection indefinitely (or at least for as long as your body can deal with taking the drugs). The problem is that during the asymptomatic phase, your body is not able to eliminate the virus entirely. And even on HAART the drugs only work for as long as you take the drugs. So despite reducing viral load to a minimum, neither your body or our current best therapy can provide a cure. Just a stopgap. And it is a stopgap that has allowed uncountable numbers of HIV patients to live longer and better quality lives, but it is ultimately not a solution to the underlying problem.
So how is it that HIV can hang on long enough to eventually overpower the immune system? And how is it that our effective anti-retroviral regimen can’t manage to destroy the infection entirely? Viral latency. HIV has a number of molecular mechanisms (primarily based on transcription control) that allow it to sit in a cell for a good deal of time before replicating and budding off to go along its merry way. When that quality is coupled with the quirk of certain T-cells to go latent and become memory-T-cells, it makes for a particularly stealthy infection. The body and the drugs can do nothing to a latent virus in a latent cell, but if either of them let their guard down, and that cell becomes active and that virus becomes active, the entire infection can re-profuse.
This is (hopefully) the last hurdle to achieving an effective and practical cure for the disease: find a way to dump the reservoirs. Preferably without killing the patient. If only that were as easy as it sounds.