Sustained plasma TNF-alpha and HIV-1 load despite resolution of other parameters of immune activation during treatment of tuberculosis in Africans.
OBJECTIVE
To determine the impact of treatment of tuberculosis on plasma HIV-1 load in African subjects and to correlate viral load with response to treatment and changes in immune activation.


METHODS
Clinical and microbiological responses, immune activation parameters and plasma HIV-1 load were determined in 20 patients with pulmonary tuberculosis and HIV-1 coinfection in Ghana, West Africa during the first 3 months of anti-tuberculosis treatment.


METHODS
Plasma HIV-1 load and markers of immune activation were determined by commercially available assays. Human leukocyte antigen (HLA)-DR incorporation into the HIV-1 envelope was measured by using an immunomagnetic capture technique.


RESULTS
Treatment of tuberculosis resulted in significant improvements in weight and haemoglobin, a high sputum smear conversion rate and marked reductions in mean plasma tumour necrosis factor (TNF) receptor-1, interleukin-6 and C-reactive protein. Furthermore, incorporation of host HLA-DR into the HIV-1 envelope decreased; this also suggested a reduction in immune activation of the cells supporting viral replication. However, of importance with regard to AIDS pathogenesis, neither mean plasma TNF-alpha nor HIV-1 load decreased significantly.


CONCLUSIONS
The failure of HIV-1 plasma load to decline significantly during the initial months of anti-tuberculosis treatment is associated with high, sustained systemic levels of TNF-alpha. The dissociation between the sustained levels of plasma TNF-alpha and the major reductions in other, diverse immune activation parameters may represent dysregulation of cytokine production in these African patients.
Lawn
S D
SD
HIV and Retrovirology Branch, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333, USA.
Shattock
R J
RJ
Acheampong
J W
JW
Lal
R B
RB
Folks
T M
TM
Griffin
G E
GE
Butera
S T
ST
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000995:Antitubercular Agents / Q000627:therapeutic use*; D005869:Ghana; D015497:HIV-1 / Q000302:isolation & purification*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019562:Viral Load
D000995:Antitubercular Agents; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha