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Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1-Infected Individuals.

Aichelburg MC, Weseslindtner L, Mandorfer M, Strassl R, Rieger A, Reiberger T, Puchhammer-Stöckl E, Grabmeier-Pfistershammer K - PLoS ONE (2015)

Bottom Line: The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015).In three of the CMV cases the CMV-QFT yielded indeterminate results.Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna, Vienna, Austria.

ABSTRACT

Background: Among HIV-1-infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1-infected subjects.

Methods: Prospective, longitudinal study in 153 HIV-1-infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months.

Results: Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results.

Conclusions: While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results.

No MeSH data available.


Related in: MedlinePlus

Tukey’s schematic boxplot showing the association between CMV-specific and mitogen IFN-gamma response and both CD4+ (A, B) and CD8+ (C, D) T cell count.CD4+ T cell count tertiles: 1st: < 115, 2nd: 115–217, and 3rd: > 217 cells/μL. CD8+ T cell count tertiles: 1st: < 478, 2nd: 478–903, and 3rd: > 903 cells/μL.
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pone.0137096.g002: Tukey’s schematic boxplot showing the association between CMV-specific and mitogen IFN-gamma response and both CD4+ (A, B) and CD8+ (C, D) T cell count.CD4+ T cell count tertiles: 1st: < 115, 2nd: 115–217, and 3rd: > 217 cells/μL. CD8+ T cell count tertiles: 1st: < 478, 2nd: 478–903, and 3rd: > 903 cells/μL.

Mentions: Individuals were grouped according to CD4+ T cell count tertiles (1st: < 115, 2nd: 115–217, and 3rd: > 217 cells/μL). CMV-specific IFN-gamma response significantly varied throughout the CD4+ T cell count tertiles (P = 0.003) (Fig 2). Post-hoc comparisons revealed, that patients in the 3rd tertile (16.5 (IQR 53.9) IU/mL) had a higher CMV-specific IFN-gamma response than patients in the 1st tertile (0.658 (IQR 23.78) IU/mL; P = 0.003). While there was a trend towards a higher CMV-specific IFN-gamma response in patients in the 3rd tertile, when compared to patients in the 2nd tertile (2.84 (IQR 19.07) IU/mL; P = 0.054), the responses of subjects in the 1st and the 2nd tertile were comparable (P = 1).


Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1-Infected Individuals.

Aichelburg MC, Weseslindtner L, Mandorfer M, Strassl R, Rieger A, Reiberger T, Puchhammer-Stöckl E, Grabmeier-Pfistershammer K - PLoS ONE (2015)

Tukey’s schematic boxplot showing the association between CMV-specific and mitogen IFN-gamma response and both CD4+ (A, B) and CD8+ (C, D) T cell count.CD4+ T cell count tertiles: 1st: < 115, 2nd: 115–217, and 3rd: > 217 cells/μL. CD8+ T cell count tertiles: 1st: < 478, 2nd: 478–903, and 3rd: > 903 cells/μL.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556191&req=5

pone.0137096.g002: Tukey’s schematic boxplot showing the association between CMV-specific and mitogen IFN-gamma response and both CD4+ (A, B) and CD8+ (C, D) T cell count.CD4+ T cell count tertiles: 1st: < 115, 2nd: 115–217, and 3rd: > 217 cells/μL. CD8+ T cell count tertiles: 1st: < 478, 2nd: 478–903, and 3rd: > 903 cells/μL.
Mentions: Individuals were grouped according to CD4+ T cell count tertiles (1st: < 115, 2nd: 115–217, and 3rd: > 217 cells/μL). CMV-specific IFN-gamma response significantly varied throughout the CD4+ T cell count tertiles (P = 0.003) (Fig 2). Post-hoc comparisons revealed, that patients in the 3rd tertile (16.5 (IQR 53.9) IU/mL) had a higher CMV-specific IFN-gamma response than patients in the 1st tertile (0.658 (IQR 23.78) IU/mL; P = 0.003). While there was a trend towards a higher CMV-specific IFN-gamma response in patients in the 3rd tertile, when compared to patients in the 2nd tertile (2.84 (IQR 19.07) IU/mL; P = 0.054), the responses of subjects in the 1st and the 2nd tertile were comparable (P = 1).

Bottom Line: The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015).In three of the CMV cases the CMV-QFT yielded indeterminate results.Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna, Vienna, Austria.

ABSTRACT

Background: Among HIV-1-infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1-infected subjects.

Methods: Prospective, longitudinal study in 153 HIV-1-infected subjects with a CD4+ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months.

Results: Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4+ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results.

Conclusions: While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4+ T cell count should be considered when interpreting CMV-QFT results.

No MeSH data available.


Related in: MedlinePlus