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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

Study profile for HIV-1 infected individuals who underwent CMV-QFT testing.CMV-QFT = Cytomegalovirus-QuantiFERON assay.
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pone.0137096.g001: Study profile for HIV-1 infected individuals who underwent CMV-QFT testing.CMV-QFT = Cytomegalovirus-QuantiFERON assay.

Mentions: One-hundred fifty-eight HIV-1–infected individuals were screened for the inclusion in this study. A total of 153 subjects underwent CMV-QFT testing, as five patients declined participation (Fig 1). The mean age was 43.6 ± 10.6 years, 72% (110/153) of the subjects were male and 28% (43/153) were female. The majority of individuals were born in Europe (82%; 125/153). Eighty subjects (52%) were smokers. Seventy-seven percent (117/153) of patients were currently on ART. HIV-1 RNA levels were below the limit of quantification (< 20 copies/mL) in 34% (52/153) of the subjects, while 24% (36/153) displayed low-level viremia (20–400 copies/mL). The mean actual and nadir CD4+ T cell counts were 167 ± 105 and 55 ± 110 cells/μL, respectively. Thirty-nine percent (60/153) of the subjects had previously been diagnosed with an AIDS-defining disease according to the Centers for Disease Control and Prevention classification [12] (Table 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)

Study profile for HIV-1 infected individuals who underwent CMV-QFT testing.CMV-QFT = Cytomegalovirus-QuantiFERON assay.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0137096.g001: Study profile for HIV-1 infected individuals who underwent CMV-QFT testing.CMV-QFT = Cytomegalovirus-QuantiFERON assay.
Mentions: One-hundred fifty-eight HIV-1–infected individuals were screened for the inclusion in this study. A total of 153 subjects underwent CMV-QFT testing, as five patients declined participation (Fig 1). The mean age was 43.6 ± 10.6 years, 72% (110/153) of the subjects were male and 28% (43/153) were female. The majority of individuals were born in Europe (82%; 125/153). Eighty subjects (52%) were smokers. Seventy-seven percent (117/153) of patients were currently on ART. HIV-1 RNA levels were below the limit of quantification (< 20 copies/mL) in 34% (52/153) of the subjects, while 24% (36/153) displayed low-level viremia (20–400 copies/mL). The mean actual and nadir CD4+ T cell counts were 167 ± 105 and 55 ± 110 cells/μL, respectively. Thirty-nine percent (60/153) of the subjects had previously been diagnosed with an AIDS-defining disease according to the Centers for Disease Control and Prevention classification [12] (Table 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