The immune response fails to control HIV early in initial virus spread
Lillian B. Cohn, Steven G. Deeks
Lillian B. Cohn, Steven G. Deeks
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Commentary

The immune response fails to control HIV early in initial virus spread

Abstract

Discontinued antiretroviral therapy (ART) results in uncontrolled HIV replication in most cases. How the virus population that persists during ART escapes immune control remains unknown. In this issue of the JCI, Mitchell and authors investigated plasmacytoid dendritic cells (pDCs) from the blood of individuals living with HIV. After ART was discontinued and as the virus began to spread, an apparently functional pDC response emerged. Notably, these pDCs were initially capable of producing high levels of type I IFN, but rapidly lost this capacity, even before the virus became readily detectable in blood. This study suggests that dysfunctional pDCs are a key initial mechanism associated with poor HIV control. These innate immune responses might be targeted in the emerging efforts to cure HIV disease.

Authors

Lillian B. Cohn, Steven G. Deeks

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Figure 1

Immune response following ART interruption.

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Immune response following ART interruption. (A) In the majority of indiv...
(A) In the majority of individuals, ART cessation results in an initial immune response that involves activation of pDCs and production of IFN. Mitchell and colleagues found that this initial immune response was followed by a period of anergy within the pDC compartment, which, they hypothesized, leads to a dysfunctional immune response and subsequent loss of viral control. (B) In contrast to the typical noncontrollers who rebound after ART, some individuals exhibit durable control (post-treatment controllers), which presumably occurs by generating and maintaining a polyfunctional, robust immune response.