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Anti-HIV Therapy is Suboptimal in Lymphoid Tissues

Alain Lafeuillade
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Posted on Wednesday, 14 December 2011
in Clinical Aspects

Professor Mario Stevenson (Miami, USA) has some interesting news to bring to the HIV research community at large. In a recent interview conducted at the 5th International Workshop on HIV Persistence, Reservoirs and Eradication Strategies, Stevenson claimed that all anti-retroviral therapies are not effective against HIV hiding in lymphoid tissues. HIV replicates the most in lymphatic tissue and resides in these same tissues to create HIV reservoirs, and in a 3-year long collaborative project, Stevenson came to this conclusion.

Here's how the study worked:  A group of HIV-positive patients on antiretroviral therapy were recruited, and lymphoid tissue from the gut and lymph nodes was taken from each person. The question is:  Does the HIV respond to antiretroviral therapy (ART) in lymphoid tissue the same way that it does in the blood?  While one or two antiretroviral medications indeed reach the tissue in the same concentrations that it does in the blood, others were shown to be relatively ineffective.  Therefore, Stevenson claims, "In tissue, it's not combination therapy.  It's mono-therapy or dual therapy."  So, how is the virus responding to ART within tissue?

For those who are on ART, the viral level in the blood is drastically reduced, and becomes undetectable within a month.  However, in some patients, there are actually higher levels of virus hiding in the lymphoid tissues—evidence that construction of HIV reservoirs has occurred.  Therefore, the response is different in the tissues than it is in the blood. "What this suggests is that the tissues provide a sanctuary—a pharmacologic sanctuary—that allows the virus to exploit those suboptimal concentrations to infect cells," Stevenson says. ART isn't shutting down virus infection completely—episodic infections are still occurring, and Stevenson claims that the reservoir can be replenished by the new infections made by the suboptimal concentrations.

Why is there such a discrepancy? There are possibilities. For example, in HIV-suppressed patients, the viral replications are continuing, but they're happening in very slow, small quantities, and at a low level. Or, there is a chronic virus source somewhere in the body—even while the virus is suppressed. These sources are infecting new cells; however, the newly-infected cells aren't then progressing to infect cells themselves. The goal is to identify where these sources are, and whether or not these tissue reservoirs are developing resistance to ART. Based on these findings, there is still a ways to go to achieve a cure for HIV.

Researchers are working hard toward HIV eradication, but there is more work to be done.

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Key words: Hiv, aids, cure, eradication, latency, persistence, reservoir, reservoirs, sanctuary
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