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Grand Rounds | Clinician's Corner

Long-term Nonprogressive Disease Among Untreated HIV-Infected Individuals:  Clinical Implications of Understanding Immune Control of HIV

Stephen A. Migueles, MD; Mark Connors, MD
JAMA. 2010;304(2):194-201. doi:10.1001/jama.2010.925.
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As of 2008, more than 33 million adults and children have been estimated to be living with human immunodeficiency virus (HIV). Among them are rare patients (<0.5%) who have remained clinically well without antiretroviral therapy after almost 20 years of infection. They maintain stable CD4 cell counts and suppressed HIV replication to levels comparable with those measured in patients receiving combination antiretroviral therapy. No known epidemiologic or behavioral factors are predictive of untreated, nonprogressive HIV infection; however, host genetics and immune response factors, most specifically HLA antigen class I–restricted HIV-specific CD8 T cells, appear to be primarily responsible for this remarkable phenotype in a majority of these individuals. These patients offer hope that durable control of HIV infection is possible and can provide important insight to inform the development of the next generation of HIV/AIDS vaccines and immune-based therapies. This article reviews clinical features of these unique patients and discusses them in the context of nonprogressors enrolled in other cohorts. Potential mechanisms underlying nonprogressive HIV infection and scientific discoveries, facilitated by the participation of these patients in clinical trials, of relevance to the design of an efficacious HIV/AIDS vaccine are also highlighted.

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Figure 1. CD4 Cell Counts and HIV-1 RNA Levels in 2 Long-term Nonprogressors
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CD4 cell counts and human immunodeficiency virus 1 (HIV-1) RNA levels are shown for the 2 patients described in the introductory text. Standard viral load testing (branched DNA, version 1; Chiron Corp, Emeryville, California) with a detection limit of 10 000 copies/mL was replaced in 1996 with an assay (ultrasensitive branched DNA, version 2; Chiron Corp) possessing a detection limit of 500 copies/mL through 1998, which preceded a newer-generation ultrasensitive assay (ultrasensitive branched DNA, version 3; Bayer Diagnostics, Tarrytown, New York) with a lower threshold of 50 copies/mL. Arrowheads refer to transient episodes of detectable viremia for patients 1 and 2. Anti–hepatitis C virus therapy, with interferon alfa-2b and ribavirin, is denoted at the top of panel A.

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Figure 2. CD4 Cell Counts and HIV-1 RNA Levels in an HCV/HIV-Coinfected Hemophiliac Patient With Lost Immune Control
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CD4 cell counts and human immunodeficiency virus 1 (HIV-1) RNA levels are shown for the patient described in the text (“Patient Characteristics” section). Standard viral load testing (branched DNA, version 1) with a detection limit of 10 000 copies/mL was replaced in 1996 with an assay (ultrasensitive branched DNA, version 2) possessing a detection limit of 500 copies/mL through 1998, which preceded an ultrasensitive assay (branched DNA, version 3) with a lower threshold of 50 copies/mL. Markers at the top of the plot indicate the 3-month period of anti–hepatitis C virus (HCV) therapy with interferon alfa-2a and ribavirin as well as antiretroviral therapy with emtricitabine, tenofovir, and raltegravir initiated in 2009.

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