MULTIPARAMETER ANALYSIS OF CLASTOGENIC FACTORS, PROOXIDANT CYTOKINES,AND INFLAMMATORY MARKERS IN HIV-1-INFECTED PATIENTS WITH ASYMPTOMATICDISEASE, OPPORTUNISTIC INFECTIONS, AND MALIGNANCIES

HIV-1-infected patients are in chronic oxidative stress and clastogeni c factors (CFs) are present in their plasma. CFs from patients with HN are formed via superoxide anion radical and stimulate further superox ide production. The pathophysiologic significance and the exact compos ition of the circulating clastogenic material in patients with HIV is unknown. Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), a re increased in the plasma of patients with HIV and TNF-alpha shows cl astogenic activity in vitro. The aim of this clinical study was to com pare levels of CF in HIV-1-positive patients with asymptomatic disease , opportunistic infections, and malignancies with those in HIV-1-negat ive control groups and to correlate CF activity with CD4(+) T cell num bers, the cytokines (TNF-alpha, interleukin-2 [IL-2], IL-6), and the i nflammatory markers (C-reactive protein [CRP], neopterin, granulocyte elastase). CFs were significantly in creased in all HIV-1-positive pat ients and in HIV-1-negative patients with malignant tumors. HIV-1-posi tive patients with Kaposi's sarcoma showed the highest CF activity in their plasma (p < 0.08). CFs appear very early in HIV infection, and t hey correlate negatively with CD4(+) T cells, which are an indicator o f disease activity. The presence of CF in the plasma of HN-infected pa tients is not a general response to a viral infection because these fa ctors are not increased in HIV-1-negative patients with viral infectio n (zoster). CFs are not specific for the HIV-1 infection; they also oc cur in HIV-1-negative patients with malignant tumors. There was a tend ency towards a positive correlation (p < 0.14) between CF and TNF-alph a, but there was no positive correlation of CF with IL-2, IL-6, CRP, e lastase, and neopterin levels. This indicates that TNF-alpha may be am ong the components of CF in HIV-1-infected patients. In addition, othe r unidentified components may contribute to the clastogenic activity o f the plasma or the composition of CF mall vary from patient to patien t. Further clinical studies with larger sample populations are necessa ry to analyze the composition of CF in HIV-1-positive patients.