Sustained plasma TNF-agr; and HIV-1 load despite resolution of other parameters of immune activation during treatment of tuberculosis in Africans

Abstract

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. 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. 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. 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-agr; nor HIV-1 load decreased significantly. 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-agr;. The dissociation between the sustained levels of plasma TNF-agr; and the major reductions in other, diverse immune activation parameters may represent dysregulation of cytokine production in these African patients.