Low Proportions of CD28− CD8+ T cells Expressing CD57 Can Be Reversed by Early ART Initiation and Predict Mortality in Treated HIV Infection
Year: 2014
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Unlike cytomegalovirus (CMV) infection and aging, human immunodeficiency virus (HIV) decreases the proportion of CD28(-)CD8(+) T cells expressing CD57. Whether this abnormality predicts mortality in treated HIV infection and can be reversed by early antiretroviral therapy (ART) remains unknown. METHODS: We sampled recently HIV-infected individuals (<6 months) and HIV-uninfected controls and compared longitudinal changes in the proportion of CD28(-)CD8(+) T cells expressing CD57 between those who initiated ART early (<6 months) vs later (≥2 years). We also assessed the relationship between this phenotype and mortality in a nested case-control study of ART-suppressed chronically infected individuals. RESULTS: Compared to HIV-uninfected controls (n = 15), individuals who were recently infected with HIV had lower proportions of CD28(-)CD8(+) T cells expressing CD57 (P < .001), and these proportions increased during ART. The early ART group (n = 33) achieved normal levels, whereas the later ART group (n = 30) continued to have lower levels than HIV-uninfected controls (P = .02). Among 141 ART-suppressed participants in the SOCA study, those in the lowest quartile of CD28(-)CD8(+) T cells expressing CD57 had 5-fold higher odds of mortality than those in the highest quartile (95% CI, 1.6-15.9, P = .007). CONCLUSIONS: Abnormally low proportions of CD28(-)CD8(+) T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: National Institutes of Health, National Institute of Mental Health, National Eye Institute, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Center for AIDS Prevention Studies, University of California, San Francisco, National Center for Advancing Translational Sciences
Awards: G1033918684, G1066646890, G1217462604, G1531094742, G1572886882, Clinical and Translational Science Institute, Impact of HIV-associated inflammation on disease, G2592733289, G349814709, Defining the Pathogenesis of Immune Deficiency in Chronic HIV Infection, G4553935269, Studies of Ocular Complications of AIDS - Coordinating Center, Clinical and Transtional Science Institute, Institute for Clinical and Translational Research, G7919633022, G7998845928, G81379742, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, CFAR Network of Integrated Clinical Systems (CNICS), AIDS Clinical Trial Group Laboratory Center, Center for AIDS Prevention Studies (CAPS), G958937280, G97119092
OpenAlex ID: W2146166475