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CD8 T-Cell Expansion and Inflammation Linked to CMV Coinfection in ART-treated HIV Infection
Published by Anton POZNAK

Updated: 15 March, 2016

Freeman ML et al. Clin Infect Dis. 2016 Feb 1;62(3):392-6.

Background. Persistent CD8 T-cell expansion, low CD4/CD8 T-cell ratios, and heightened inflammation persist in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) infection and are associated with increased risk of morbid outcomes. This study explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection.

Methods. Absolute CD4 and CD8 T-cell counts were abstracted from clinical records and compared among 32 HIV-infected CMV-seronegative subjects, 126 age, CD4 and gender-matched HIV-infected CMV-seropositive subjects, and among 21 HIV-uninfected controls (9 CMV-negative, 12 CMV-positive). Plasma inflammatory indices were measured in a subset by ELISA.

Results. HIV-infected patients were receiving ART for a median duration of 3.15 years and had undetectable plasma HIV levels (typically below 50 copies/mL). Median CD8 counts/µL were higher in HIV-positive/CMV-positive patients (795) than in HIV-positive/CMV-negative subjects (522, P = .006) or in healthy controls (451, P = .0007), whereas absolute CD8 T-cell counts among the HIV-infected CMV seronegative subjects were not different from those among healthy controls ( P > .99), suggesting that the expansion of circulating CD8 T cells that is a hallmark of ART-treated HIV infection is specifically linked to coinfection with CMV. Consequently, coinfection with HIV and CMV resulted in a significantly lower CD4/CD8 ratio than was seen among HIV-infected CMV-seronegative subjects ( P = .004). As both increased circulating CD8 T-cell numbers and low CD4/ CD8 ratios are associated with poor clinical outcomes in ART-treated HIV infection, their findings implicate CMV coinfection as a possible driver of non-AIDS morbidities in treated HIV disease. Higher plasma levels of IP-10 ( P = .0011), TNF-RII ( P = .0002), and D-dimer ( P = .0444) were also found in coinfected patients than in HIV-positive/CMV-negative subjects. Plasma levels of IL-6, a powerful predictor of morbid outcomes in treated HIV infection were not different ( P = .8389) between the CMV-seropositive and seronegative HIV-infected groups.

Similarly, levels of sCD14 were comparable between CMV-seronegative CMV-seropositive ART-treated HIV-infected subjects, suggesting that CMV coinfection is not central to microbial translocation/monocyte activation in ART-treated HIV infection.

Conclusions. CMV infection is associated with higher CD8 T-cell counts, resultant lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV infection. CMV infection may contribute to risk for morbid outcomes in treated HIV infection.