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ARTICLE

What Issues Are We Still Facing with Curing HIV?

JAN 01, 2017 | KENGO INAGAKI, MD
A plausible explanation for the apparent cure and subsequent rebound of HIV viremia is that the virus was “hiding” somewhere in the body. Indeed, HIV’s ability to cause latent infection is a major barrier to cure. After HIV infects the host cell, its genome can be integrated into that cell, where it is then called a “provirus” or “proviral DNA” and can remain replication-competent but transcriptionally-silent, mainly in long-lived memory CD4+ T cells.8 These latently infected cells can serve as the “reservoir” for HIV. In this context, the Mississippi baby can be viewed as a case in which very early initiation of ART likely prevented widespread establishment of a viral reservoir in the host.5 Similarly, it would be plausible to consider that bone marrow-ablative conditioning chemotherapy required for HSCT would reduce the size of the HIV reservoir in the body enough to delay viral rebound7 and that in certain situations where donor cells possess property that confers resistance to HIV, cure may be possible.3
 
The concept that early initiation of ART and the resulting smaller viral reservoir can be beneficial, as seen in the case of the Mississippi baby, is further supported by the observation of posttreatment controllers in the VISCONTI (Viro-Immunological Sustained CONtrol after Treatment Interruption) study.9 These individuals were generally started on ART during the acute phase of infection and sustained undetectable or very low viral load in the blood after cessation of ART, despite the evidence of remaining HIV infection in the host cells. Also in this group, a perinatally infected patient who was started on ART at 3 months of age has had very low level viremia (less than 50 copies per ml) without evidence of disease progression for 12 years after cessation of ART.10 However, posttreatment controllers have not been reliably reproducible. The window of opportunity to initiate ART during the acute phase of infection is not open to everyone as most HIV-infected patients seek clinical care after HIV has established infection, when it is too late to attempt to restrict viral reservoir size.
 
Perhaps the most studied approach, to date, for addressing HIV latency and reservoir is the so-called “shock-and-kill” strategy. With this, researchers attempt to reverse the latency by using “latencyreversing agents,” such as histone deacetylase inhibitors (HDIs),11,12 disulfiram,13 protein kinase C agonists,14 and Toll-like receptor 7 agonist among others,15 and have immunotherapy or an activated host’s immunity eliminate the latent HIV-infected cells. So far, there has been no published data available for the success of this approach in humans, although there are animal studies that seem promising for future application to humans.16,17 However, The Sunday Times reported in October 2016 that a British individual who was enrolled in the RIVER (Research in Viral Eradication of HIV Reservoirs) study, which utilizes the shock-and-kill approach, may have been cured of HIV.18
 


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Is there a cure? How long until we find it? And will it work for the majority of people living with HIV?