Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART.
OBJECTIVE
Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy.


METHODS
We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette-Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array.


METHODS
A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints.


RESULTS
Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-gamma levels in culture supernatants did not reflect this response; however, a decline in TNF-alpha was observed.


CONCLUSIONS
This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.
Kampmann
Beate
B
School of Child and Adolescent Health, University of Cape Town, and Red Cross Children's Hospital, Rondebosch, Cape Town 7701, Republic of South Africa.
Tena-Coki
Gwen N
GN
Nicol
Mark P
MP
Levin
Michael
M
Eley
Brian
B
D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D005260:Female; D006678:HIV / Q000276:immunology / Q000502:physiology; D006801:Humans; D007223:Infant; D008297:Male; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology*; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000097:blood / Q000276:immunology* / Q000821:virology; D019562:Viral Load
D016207:Cytokines