The magnitude of interferon-gamma responses to human cytomegalovirus is predictive for HIV-1 disease progression.
BACKGROUND
Human cytomegalovirus (HCMV) infection has been strongly associated to HIV-1 progression. We have investigated whether the magnitude of the overall peripheral blood mononuclear cell responses to HCMV stimulation correlated with HIV-1 progression.


METHODS
Blood samples were collected from 75 HIV-1-positive individuals on highly active antiretroviral therapy with CD4 count>500 cells per cubic millimeter and undetectable HIV RNA just before interrupting treatment. Specific interferon-gamma (IFN-gamma) HCMV cell responses were measured by an enzyme-linked immunospot (ELISPOT) assay. The results were analyzed by Kaplan-Meier survival curves, contingency tests, and the Cox proportional hazard models to evaluate the predictive value of peripheral blood responses to HCMV and the length of time that patients were off treatment.


RESULTS
Patients were stratified into those with weak (<500 spot-forming units) or strong (>500 spot-forming units) IFN-gamma responses to HCMV. During the 3-year follow-up, 51% of patients with strong responses remained untreated compared with 14% of patients with weak HCMV responses (P=0.0015). Length of time without therapy was also longer in patients with stronger responses (hazard ratio=2.08; P=0.001). HCMV responses were still predictive of restarting therapy after adjusting for the CD4 nadir counts.


CONCLUSIONS
Specific IFN-gamma responses to HCMV may be employed as a predictive useful marker for the evolution of HIV-1 infection.
Darwich
Laila
L
Fundació IrsiCaixa-HIVACAT Fundació, Hospital Germans Trias i Pujol, Badalona, Spain.
Cabrera
Cecilia
C
Romeu
Joan
J
Martinez-Picado
Javier
J
Esté
José A
JA
Tural
Cristina
C
Bellido
Rocio
R
Clotet
Bonaventura
B
Angulo
Ana
A
Ruiz
Lidia
L
Bofill
Margarita
M
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism; D004279:DNA, Viral; D018450:Disease Progression; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D014766:Viremia
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D007371:Interferon-gamma