Low production of interferon gamma is related to disease progression in HIV infection: evidence from a cohort of 347 HIV-infected individuals.
A total of 347 HIV-seropositive individuals attending the Department of Infectious Diseases at Rigshospitalet in Copenhagen and 110 age- and sex-matched healthy controls not at risk for HIV infection were included in this study. Interferon gamma (IFN-gamma) production was measured in whole blood of 223 HIV-seropositive individuals (68 had developed AIDS at enrollment) and 99 healthy sex- and age-matched controls 4.5 hr after challenge with phytohemagglutinin. HIV-infected individuals for whom IFN-gamma production was measured were followed with a median follow-up time of 2.89 years (range, 0.02-4.54 years) from the date of enrollment. Survival analysis was performed considering three different end points: (1) a CD4 count below 100 cells/mm3, (2) an AIDS diagnosis defined according to the 1993 Centers for Disease Control definition, and (3) death. The production of IFN-gamma was highly increased in the blood of HIV-infected individuals without AIDS, but decreased in the blood of AIDS patients (both compared to controls). In the HIV-infected individuals, the total production of IFN-gamma was positively correlated with the number of CD8+ T lymphocytes and with the number of CD16+/CD56+ natural killer cells and negatively correlated with serum levels of beta2-microglobulin. Low levels of IFN-gamma production were associated with an increased risk of experiencing a CD4 count below 100 cells/m3 and death, analyzed in both univariate analysis and in multivariate analysis adjusting for CD4 counts and age. Thus, changes in production of IFN-gamma seem to be truly related to the risk for disease progression in HIV infection.
Ullum
H
H
Department of Infectious Diseases, Rhima Centre, Rigshospitalet, Copenhagen N, Denmark. infdishu@rh.dk
Cozzi Lepri
A
A
Bendtzen
K
K
Victor
J
J
Gøtzsche
P C
PC
Phillips
A N
AN
Skinhøj
P
P
Klarlund Pedersen
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D007371:Interferon-gamma