Antiviral Inhibitory Capacity of CD8+ T cells Predicts the Rate of CD4+ T-Cell Decline in HIV-1 Infection

• Published in: The Journal of infectious diseases 2012-08, Vol.206 (4), p.552-561
• Main Authors: Yang, Hongbing, Wu, Hao, Hancock, Gemma, Clutton, Genevieve, Sande, Nellia, Xu, Xiaoning, Yan, Huiping, Huang, Xiaojie, Angus, Brian, Kuldanek, Kristin, Fidler, Sarah, Denny, Thomas N., Birks, Jacqueline, McMichael, Andrew, Dorrell, Lucy
• Format: Article
• Language: English
• Subjects: Adult; AIDS; Antivirals; Biological and medical sciences; Biomarkers; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes - immunology; Cultured cells; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV 1; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Infections; Infectious diseases; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Prognosis; T lymphocytes; Vaccination; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral load; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis379

Background. Rare human immunodeficiency virus type 1 (HIV-1)—infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell—mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown. Methods. We measured CD8+ T-cell—mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1—seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline. Results. There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4 + T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002). Conclusions. The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation.