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CD4-Cell Depletion in an HIV-1 Elite Controller

A case report of an HIV-1 elite controller with progressive CD4-cell depletion

HIV-1 elite controllers have been the focus of intense research in the HIV field. These individuals have a unique ability to spontaneously control virus replication in the absence of antiretroviral drugs and are usually able to preserve high CD4-cell counts for prolonged periods of time.

In this report, researchers describe a man coinfected with HIV and hepatitis C virus (HCV) who has not received antiretroviral therapy (ART) since 2000. During the past 10 years, most of his plasma viral load measurements have been below the limit of detection for standard ultrasensitive HIV RNA assays (<50 copies/mL), but his CD4 count has declined from >400 cells/mm³ to <200 cells/mm³.

Amplification of HIV from culture supernatant of CD4 lymphocytes revealed a replication-competent clade B virus that did not harbor mutations in the nef gene. In addition, markers of immune activation (HLA-DR and CD38) on CD4 and CD8 cells were present at significantly higher levels than those seen in elite controllers with high CD4-cell counts or in HIV-uninfected individuals. Immune activation in this patient could not be explained by microbial translocation, as levels of lipopolysaccharide (LPS), LPS binding protein, soluble CD14, and endotoxin-core antibody were all low. Researchers detected high numbers of HIV-specific CD8-lymphocyte responses targeting HIV gag proteins.

Comment: The authors of this case report suggest that, in the absence of measurable plasma viral load, CD4-cell decline is probably the result of immune activation (ACC Feb 25 2008), which has been associated with disease progression. The mechanisms behind CD4-lymphocyte loss and immune activation in this case remain unknown. Possibilities include other active chronic viral infections and their consequences (such as HCV infection and liver cirrhosis), ongoing HIV replication in sequestered sites, and chronic low-level plasma viremia that is below the limit of detection of currently available assays. How combination ART might benefit this patient is unclear; presumably, by reducing antigen load that is not apparent by our current plasma HIV RNA assays, one might alter immune system homeostasis and halt CD4-cell loss. Regardless of the mechanisms involved, given the clinical consequences of low CD4-cell counts, clinicians faced with patients like this one should consider the potential benefits of starting ART.

— Florencia Pereyra, MD

Dr. Pereyra is Instructor of Medicine at Harvard Medical School and a junior faculty member at the Partners AIDS Research Center, Massachusetts General Hospital, and Division of Infectious Diseases at the Brigham and Women’s Hospital, Boston.

Published in Journal Watch HIV/AIDS Clinical Care April 7, 2008

Citation(s):

Andrade A et al. CD4⁺ T cell depletion in an untreated HIV type 1–infected human leukocyte antigen–B*5801–positive patient with an undetectable viral load. Clin Infect Dis 2008 Mar 4; [e-pub ahead of print]. (http://dx.doi.org/10.1086/529387)

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