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In Search of a (Functional) Cure

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Science Translational Medicine  10 Apr 2013:
Vol. 5, Issue 180, pp. 180ec61
DOI: 10.1126/scitranslmed.3006267

Antiretroviral therapy suppresses HIV replication but does not eliminate the “latent reservoir” of HIV in infected cells. As such, there is no cure for HIV. But there is a group of patients, known as “HIV controllers,” who are able to spontaneously control HIV replication for many years without antiretroviral therapy. Understanding whether and how other HIV-infected patients are able to control the virus without therapy may provide insight toward the eventual development of a “functional cure” for HIV, with which patients who still have infected cells can control HIV replication without therapy.

Sáez-Cirión and colleagues describe, among 70 HIV-infected adults who received very early antiretroviral therapy (within 10 weeks of infection), 14 patients who have controlled HIV replication for many years after stopping therapy. These patients, who received antiretroviral therapy for a median 3 years before it was stopped, had more severe infection and a different genetic makeup than those of traditional HIV controllers. The authors analyzed these patients’ lymphocytes (white blood cells) to characterize the latent HIV reservoir and found that these patients had a much smaller latent reservoir than those of other HIV-infected patients even years after treatment was stopped, similar to that seen in HIV controllers. Interestingly, the latent reservoir was less likely to form in cell types with a long lifespan, which are thought to contain the latent reservoir in most HIV-infected patients. These findings suggest that development of therapeutic or immunologic strategies to reduce or prevent the formation of the latent reservoir, particularly in long-lived cells, may help achieve a functional cure in other patients.

This study by Sáez-Cirión et al. demonstrates a small but significant proportion of HIV-infected patients who, when treated very early, may achieve remission and a small latent viral reservoir. The findings also provide further support for earlier HIV treatment. Additional studies of patients treated very early are required to determine how some of these patients are able to achieve viral control. Such mechanistic insight may lead to a functional cure for HIV patients.

A. Sáez-Cirión 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 Pathogens 9, e1003211 (2013). [Full Text]

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