Elite and posttreatment controllers, two facets of HIV control

Abstract

Purpose of review: The quest for HIV-1 cure could take advantage of the study of rare individuals that control viral replication spontaneously (elite controllers) or after an initial course of antiretroviral therapy (posttreatment controllers, PTCs). In this review, we will compare back-to-back the immunological and virological features underlying viral suppression in elite controllers and PTCs, and explore their possible contributions to the HIV-1 cure research.

Recent findings: HIV-1 control in elite controllers shows hallmarks of an effective antiviral response, favored by genetic background and possibly associated to residual immune activation. The immune pressure in elite controllers might select against actively transcribing intact proviruses, allowing the persistence of a small and poorly inducible reservoir. Evidence on PTCs is less abundant but preliminary data suggest that antiviral immune responses may be less pronounced. Therefore, these patients may rely on distinct mechanisms, not completely elucidated to date, suppressing HIV-1 transcription and replication.

Summary: PTCs and elite controllers may control HIV replication using distinct pathways, the elucidation of which may contribute to design future interventional strategies aiming to achieve a functional cure.

Box 1

no caption available

FIGURE 1

Characteristics of elite controllers, posttreatment controllers and antiretroviral therapy-treated patients. Top panel: elite controllers show a strong, effective immune response against HIV-1, primarily based on CD8 T cells. PTCs, on the contrary, may display a less pronounced antiviral immunity, even though great heterogeneity has been detected in the immunological features of these individuals. Middle panel: both elite controllers and PTCs harbor a significantly lower frequency of HIV-1-infected cells in blood when compared with ART-treated patients. Lower panel: HIV-1 reservoir in elite controllers is dominated by poorly inducible proviruses showing low transcriptional activity. Features of HIV-1 reservoir in PTCs are largely unknown but based on preliminary data and on paucity of antiviral immune responses detected ex vivo in these patients, we can speculate that a reduced transcriptional activity of intact reservoirs might be associated to natural control of HIV-1 replication in this group. ART, antiretroviral therapy; PTCs, posttreatment controllers.