Tuberculosis treatment in HIV infected Ugandans with CD4 counts>350 cells/mm reduces immune activation with no effect on HIV load or CD4 count.
BACKGROUND
Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.


METHODS
This prospective cohort study, composed of participants within a larger phase 3 open-label randomized controlled clinical trial, measured the impact of TB treatment on immune activation in persons with non-advanced HIV infection (CD4>350 cells/mm3) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB.


RESULTS
Expression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period.


CONCLUSIONS
TB therapy leads to measurable decreases in immune activation in persons with HIV/TB co-infection and CD4 counts>350 cells/mm3.
Mahan
C Scott
CS
Tuberculosis Research Unit, Case Western Reserve University School of Medicine, and University Hospitals-Case Medical Center, Cleveland, Ohio, United States of America. csmahan@gmail.com
Walusimbi
Maria
M
Johnson
Denise F
DF
Lancioni
Christina
C
Charlebois
Edwin
E
Baseke
Joyce
J
Chervenak
Keith A
KA
Mugerwa
Roy D
RD
Havlir
Diane V
DV
Mayanja-Kizza
Harriet
H
Whalen
Christopher C
CC
Boom
W Henry
WH
D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*; D014454:Uganda; D019562:Viral Load / Q000276:immunology*; D055815:Young Adult
D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin