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 H IV-1 load in African subjects and to correlate viral load with response to treatment and changes in immune activation. Design: Clinical and microbiological responses, immune activation parameter s and plasma HIV-1 load were determined in 20 patients with pulmonary tuber culosis and HIV-1 coinfection in Ghana, West Africa during the first 3 mont hs of antituberculosis treatment. Methods: Plasma HIV-1 load and markers of immune activation were determined by commercially available assays. Human leukocyte antigen (HLA)-DR incorpo ration into the HIV-1 envelope was measured by using an immunomagnetic capt ure technique. Results: Treatment of tuberculosis resulted in significant improvements in weight and haemoglobin, a high sputum smear conversion rate and marked redu ctions in mean plasma tumour necrosis factor (TNF) receptor-1, interleukin- 6 and C-reactive protein. Furthermore, incorporation of host HLA-DR into th e HIV-1 envelope decreased; this also suggested a reduction in immune activ ation of the cells supporting viral replication. However, of importance wit h 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 duri ng the initial months of anti-tuberculosis treatment is associated with hig h, sustained systemic levels of TNF-alpha. The dissociation between the sus tained levels of plasma TNF-alpha and the major reductions in other, divers e immune activation parameters may represent dysregulation of cytokine prod uction in these African patients. (C) 1999 Lippincott Williams & Wilkins.