Where HIV Hides

While the HIV reservoir has yet to be fully mapped, we know HIV targets key immune cells of the body. The cells travel along an inner body highway of lymphatic vessels the size of capillaries that flow next to the bloodstream and are found in lymph, a clear fluid that bathes body tissues and must be drained. The lymph gets dumped back into the bloodstream. That’s how B and T cells move between the blood and tissue; as HIV infects T cells, the virus is transported into tissue sites throughout the body.

A small percentage of these activated T cells will later revert to a resting state to become “memory” T cells that harbor particles of HIV and make up the HIV reservoir. Rather than a single site, the HIV reservoir exists in tissue throughout the body.

Today we know that the bulk of HIV viral particles in the reservoir are actually fragments that can’t reproduce; a small fraction are “replication competent,” or infectious. So we’re actually targeting a very small percentage of an already small dormant HIV pool. That doesn’t make it any easier to find the latent HIV particles because the hiding places are all over the body.

The lymphoid system is made up of three main cell types found in lymphoid organs: Lymphocyte (B and T cells), epithelial, and stromal cells. Other cells in tissue include bone-marrow derived macrophages and antigen-presenting cells.

In the body, lymphoid organs serve a frontline role in fighting infection. They are a pit stop for immune cells to stop, trap, and kill invading and disease-causing organisms. Normally, circulating T cells return to the blood from the lymph nodes within a few hours.

Other primary lymphoid organs are fetal bone marrow and the liver that produce B cells, and the thymus, which produces T cells. Secondary lymph organs include the spleen, adult bone marrow, and gut- and mucosal-associated lymphoid tissue (GALT and MALT) that line many organs, including the Peyer’s Patches of the small intestine, digestive tract, colon, appendix, tonsils, adenoids, retinas, and the testes and male genital tracts. The brain, fed by blood and cerebrospinal fluid, is considered a special sanctuary site that is protected by a thick “blood-brain” barrier. Some HIV drugs can cross that barrier better than others. But the brain is an HIV reservoir site. —ACD