HIV-specific CD4+ T cells may contribute to viral persistence in HIV controllers.

Abstract

BACKGROUND:

Human immunodeficiency virus (HIV)--infected individuals maintaining plasma HIV RNA levels <75 copies/mL in the absence of therapy ("HIV controllers") often maintain high HIV-specific T cell responses, which likely contribute to the control of viral replication. Despite robust immune responses, these individuals never eradicate HIV infection. We hypothesized that HIV-specific CD4(+) T cells might serve as target cells for HIV, contributing to viral persistence in this setting.

METHODS:

We measured frequencies of activated (CD38(+) HLA-DR(+)) and HIV Gag-specific CD4(+) and CD8(+) T cells and plasma- and cell-associated levels of HIV RNA and DNA in a cohort of 38 HIV controllers.

RESULTS:

Although there was no evidence of a relationship between the extent of low-level viremia and the frequency of either activated or HIV-specific CD4(+) T cells, controllers with higher HIV-specific CD4(+) T cell frequencies had higher cell-associated HIV DNA levels (ρ = 0.53; P = .019). Higher activated CD4+ T cell frequencies were also associated with higher levels of cell-associated DNA (P = .027) and RNA (P = .0096). However, there was no evidence of a relationship between cell-associated HIV RNA or DNA levels and HIV-specific CD8(+) T cell frequencies.

CONCLUSIONS:

These data support a model in which strong HIV-specific CD4(+) T cell responses in HIV controllers, while contributing to a potent adaptive immune response, may also contribute to viral persistence, preventing the natural eradication of HIV infection.

• Authors: Peter W Hunt, Hiroyu Hatano, Elizabeth Sinclair, Tzong-Hae Lee, Michael P Busch, Jeffrey N Martin, Joseph M McCune, Steven G Deeks
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 52 Issue 5 Pg. 681-7 (Mar 01 2011) ISSN: 1537-6591 [Electronic] United States
• PMID: 21245154 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• HLA-DR Antigens
• RNA, Viral
• gag Gene Products, Human Immunodeficiency Virus
• ADP-ribosyl Cyclase 1

Topics

• ADP-ribosyl Cyclase 1 (analysis)
• Adult
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• DNA, Viral (blood)
• Female
• HIV (immunology)
• HIV Infections (immunology)
• HIV Long-Term Survivors
• HLA-DR Antigens (analysis)
• Humans
• Male
• Middle Aged
• RNA, Viral (blood)
• Viral Load
• gag Gene Products, Human Immunodeficiency Virus (immunology)