What is an elite suppressor in the context of Human Immunodeficiency Virus (HIV)?

Elite Suppressors in HIV Infection

An elite suppressor (also called "elite controller") is a rare HIV-infected individual who maintains persistently undetectable viral loads (HIV RNA <50 copies/mL) without antiretroviral therapy. 1

Definition and Prevalence

• Elite controllers represent approximately 0.2-0.5% of all HIV-infected individuals 2
• They are formally defined as patients with confirmed HIV infection who maintain persistent undetectable HIV RNA levels without receiving antiretroviral therapy 1
• Some definitions use a threshold of <50 copies/mL, while others may use <40-75 copies/mL depending on assay sensitivity 3, 2

Mechanisms of Viral Control

Elite suppressors achieve viral control through multiple mechanisms, though these are not fully understood:

• Lower viral reservoir burden: Elite suppressors harbor significantly lower levels of integrated HIV DNA compared to patients on antiretroviral therapy, despite similar total HIV DNA levels 4
• High levels of unintegrated viral DNA: These patients frequently have elevated 2-LTR circular HIV DNA forms, suggesting ongoing low-level viral replication that fails to establish productive infection 4
• Reduced viral fitness: Envelope glycoproteins from elite suppressors demonstrate decreased entry efficiency and slower entry kinetics compared to viremic progressors 5
• Enhanced immune responses: Many elite controllers have robust HIV-specific CD8+ T cell responses, though this is not universal 6

Clinical Characteristics and Risks

Despite undetectable viral loads, elite controllers are NOT free from HIV-related complications and should still be considered for antiretroviral therapy. 1

Important clinical considerations:

• Persistent immune activation: Elite controllers maintain higher levels of immune activation compared to HIV-negative individuals and even compared to patients achieving viral suppression with ART 1
• Increased cardiovascular risk: They have elevated risk of cardiovascular disease compared to individuals on suppressive ART 1
• Higher hospitalization rates: Elite controllers experience increased rates of hospitalization compared to virologically suppressed patients on therapy 1
• Loss of control over time: Many elite controllers eventually lose their ability to suppress HIV, leading to CD4+ T cell depletion and immunologic dysfunction 3, 2
• AIDS progression: Some elite controllers can progress to AIDS-defining conditions despite maintaining low viral loads 3

Treatment Recommendations

The decision to initiate antiretroviral therapy in elite controllers remains controversial but is increasingly recommended. 1

Rationale for treatment:

• Elite controllers may benefit from ART because they maintain higher immune activation levels than patients on suppressive therapy 1
• They face increased cardiovascular disease risk and hospitalization rates compared to treated patients 1
• Treatment can further reduce already-low levels of viral replication and potentially decrease immune activation 1

Important caveats:

• The 2016 International Antiviral Society-USA Panel guidelines note that "initiation of treatment, however, is" [text appears incomplete in source, suggesting ongoing debate] 1
• Individual patient factors including CD4 count trends, presence of comorbidities, and patient preference should inform the decision 1
• If treatment is deferred, close monitoring for loss of viral control is essential 3, 2

Diagnostic Challenges

• Elite controllers can present diagnostic challenges during acute infection, as rapid antibody/antigen tests may be negative or equivocal despite detectable viremia 6
• Viral load testing is essential for diagnosis in suspected acute infection cases that may represent emerging elite control 6
• Ultra-sensitive viral load assays may detect very low-level viremia (e.g., <1 copy/mL) even in established elite controllers 6