Persistence of High Percentage of Peripheral Activated CD8+ T Cells Predict Cytologic HPV-Related Dysplasia in cART-Treated, HIV-Positive Subjects
Articolo
Data di Pubblicazione:
2022
Citazione:
Persistence of High Percentage of Peripheral Activated CD8+ T Cells Predict Cytologic HPV-Related Dysplasia in cART-Treated, HIV-Positive Subjects / D. Mondatore, F. Bai, M. Augello, M. Giovenzana, A. Pisani Ceretti, V. Bono, E. Opocher, A. d’Arminio Monforte, G.C. Marchetti, C. Tincati. - In: OPEN FORUM INFECTIOUS DISEASES. - ISSN 2328-8957. - 9:4(2022 Apr 01), pp. ofac046.1-ofac046.8. [10.1093/ofid/ofac046]
Abstract:
Background People with HIV are at increased risk of human papillomavirus (HPV) disease progression, given the persistence of immune activation and residual inflammation despite effective combination antiretroviral therapy (cART). Whether a low CD4:CD8 T-cell ratio, known to mirror peripheral immune dysfunction, is associated with squamous intraepithelial lesions (SILs) is unknown. Methods This was a retrospective cohort study on cART-treated HIV-positive subjects undergoing screening for HPV-related dysplasia (anal/cervical cytology and HPV genotyping). SIL was defined as the presence of either atypical squamous cells of undetermined significance (ASCUS), low-grade SILs, or high-grade SILs. Demographic and viro-immunological parameters (T-cell count, CD4:CD8 T-cell ratio, CD8+ CD38+ T-cell percentage) at the time of screening were analyzed by the chi-square test, Mann-Whitney test, and multivariate logistic regression analysis. Results A total of 419 cART-treated subjects were included. Half of the patients had cervical/anal SIL. Individuals with SIL were more commonly males, were men who have sex with men, were coinfected with Treponema pallidum, had been treated with integrase inhibitor (INSTI)-based cART regimens, and had a shorter time since HIV diagnosis and cART initiation than subjects with normal cytology. CD38+ CD8+ T-cell percentage, but not the CD4:CD8 T-cell ratio, correlated with SILs. HPV infection, especially with multiple and high-risk genotypes, was confirmed to be associated with SIL. In multivariate analysis, the only factors independently associated with cervical/anal dysplasia were HPV infection and harboring higher percentages of peripheral activated CD38+ CD8+ T cells. Conclusions HPV infection is the major driver of dysplasia in the setting of HIV infection. In this study, CD8+ CD38+ T cells were an independent predictor of dysplasia in cART-treated subjects, while CD4:CD8 T-cell ratio was not. In the setting of HIV-HPV coinfection, CD4:CD8 T-cell ratio may not fully capture the alterations of HPV-specific immunity.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
activated CD8+ CD38+ T cells; CD4:CD8 ratio; cervical-anal dysplasia; HIV infection; HPV infection;
Elenco autori:
D. Mondatore, F. Bai, M. Augello, M. Giovenzana, A. Pisani Ceretti, V. Bono, E. Opocher, A. d’Arminio Monforte, G.C. Marchetti, C. Tincati
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