Antiretroviral Treatment for HIV Elite Controllers?

Main Article Content

Ezequiel Ruiz-Mateos
Eva Poveda
Michael M. Lederman

Abstract

In most HIV-infected persons, the natural history of untreated infection is one of sustained viremia, progressive CD4 T cell depletion with resultant morbidity and mortality. The advent of effective combination antiretroviral therapy (ART) that controls HIV replication has altered this landscape dramatically. Yet a rare population of HIV-infected persons—elite controllers (EC)—can control HIV replication such that plasma levels of virus are “undetectable” without ART. The EC phenotype is heterogeneous, with some subjects durably controlling the virus—persistent elite controllers—and some eventually losing viral control—transient elite controllers. Overall, EC tend to have robust HIV-specific T cell responses and in some cases, mainly in transient elite controllers, elevated activation and inflammation indices that diminish with ART suggesting that endogenous defenses against this persistent pathogen come at the cost of heightened activation/inflammation. A limited data set suggests that cardiovascular disease risk as well as the occurrence of other morbid events may be greater in the overall EC population than in treated HIV infection. ART in EC decreases activation indices but does not appear to increase circulating CD4 T cell numbers nor do we know if it alters clinical outcomes. Thus, it is difficult to recommend or discourage a decision to start ART in the EC population but the authors lean toward treatment particularly in those EC whose activation indices are high and those who are progressively losing circulating CD4 T cell numbers. Biomarkers that can reliably predict loss of virologic control and immune failure are needed.

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Section
Reviews
Author Biography

Michael M. Lederman, Case Western Reserve University; Associate Director, Center for AIDS Research, UH Cleveland Medical Center

Dr. Lederman has served as intern, resident, chief resident in Medicine and fellow in Infectious Diseases at Case Western Reserve University where he joined the faculty in 1980. He is a member of the American Association of Immunologists, the Infectious Diseases Society of America, the HIV Medicine Association and is a councilor of the Clinical Immunology Society. He is on the editorial boards of AIDS, the Journal of AIDS and Clinical Immunology.

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