What Is a Latent HIV Reservoir?

Researchers Aim to "Kick" HIV Out of Its Hiding Places

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Photo Credit: International AIDS Vaccine Initiative (IAVI)

Latent reservoirs are the cells of the body where HIV is able to hide (or "persist") even in the face of optimal antiretroviral therapy. These cellular reservoirs are located throughout numerous organ systems, including the brain, lymphoid tissue, bone marrow and genital tract.

In its latent (or "proviral") state, HIV can integrate its genetic material into the DNA of a host cell, but rather than killing it, simply replicates along with the host.

Unlike free-circulating virus, these hidden proviruses cannot be detected by the body's immune system. Instead the viral genome is carried from generation to generation, able to reactivate when triggered by a collapse in immune function.

It is, in fact, the body's immune response that provides HIV its cellular havens. When an immune response is activated  in presence of HIV, the body will generate CD4 T-cells which, ironically, are the primary target for infection. Cells already infected with HIV will proliferate, producing more HIV-infected cells and expanding the viral reservoir.

It is the persistence of these hidden viruses that continue to thwart efforts to develop a cure for the disease.

Strategies to Clear Latent Reservoirs

The biggest challenge facing researchers today is finding the means by which to activate and purge HIV from its proviral reservoirs, leaving it exposed to any number of theoretical eradication strategies.

While ART is able to deplete these reservoirs over time, it does so very slowly. Mathematical models have shown that it would take between 60 to 80 years for complete eradication to be achieved.

Increasingly, researchers are looking into the use of certain drugs that appear to stimulate the activation of latent HIV.

Among them are agents called HDAC inhibitors, which have long been used as mood stabilizers and anti-epileptics.

And while there have been successes in the activation of latent HIV, scientists are not even yet certain how big these reservoirs are or what other cells might  provide HIV a hiding place. It is, therefore, impossible to know if these reservoirs have been truly cleared by these chemical agents.

Recent research, in fact, has shown that while certain HDAC inhibitor drugs have the ability to activate latent HIV, there is no real evidence that such activation has even reduced the size of the reservoirs.

Other scientists,meanwhile, question whether "kicking" HIV from its reservoirs will be enough to achieve eradication. As a result, a number of research teams are exploring agents which appear able to kill the newly released virus with minimal toxicity. Among the more promising candidates is acitretin, a form of vitamin A currently used to treat severe psoriasis in adults.

Consequences of Latent Persistency

One of the more frustrating aspects of viral latency is that, even in its proviral state, the very presence of HIV within cells triggers an persistent inflammatory response.

Even if a person is on effective HIV therapy and is able to maintain an undetectable viral load, this low-level chronic inflammation can progressively effect the way that cells and tissues replicate, effectively speeding up the aging process.

The process, called premature senescence, is the reason why people with long-term HIV infection are at increased risk of cancers, heart disease, bone frailty, and neurocognitive disorders—and often 10 to 15 years earlier than what would be expected in the general population.


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Sáez-Cirión, A.; Bacchus, C.; Hocqueloux, L.; et al. "Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study." PLoS Pathology. March 14, 2013; 0(3):e1003211.

Søgaard, O.; Graverson, M.; Leth, S.; et al. "The HDAC inhibitor romidepsin is safe and effectively reverses HIV-1 latency in vivo as measured by standard clinical assays." 20th International AIDS Conference; July 22, 2014; Melbourne, Australia; abstract TUAA0106LB.

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