All patients in groups 14 survived 6 weeks of follow up. worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-, CRP and Compound K low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an impartial predictor in multivariate analysis. == Conclusion == High serum concentrations of TNFR p55, IFN-, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding Compound K the cause of TNFR p55, IFN- and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa. == Background == The HIV and AIDS pandemic in sub-Saharan Africa is usually a major public health burden, causing high mortality and interpersonal disruption. In urban Zambian women aged 3034 years, HIV seroprevalence is as high as 42.5% [1]. Recently, major progress has been achieved in rolling out highly active anti-retroviral therapy (HAART) in Zambia, but early mortality (within 30 or even 90 days of initiating HAART) remains a challenge [2]. The causes for this mortality are unknown, but may include undiagnosed opportunistic infections, nutritional impairment, or immune consequences of HIV which might not respond quickly to HAART. Even in developed countries, patients on HAART are still at increased risk of diarrhoea [3] and in much of sub-Saharan Africa, especially where HAART coverage is usually far from complete, diarrhoeal disease remains a major contributor to mortality. We have previously shown that nutritional status is an important prognostic indicator in patients Compound K with AIDS-related diarrhoea[4], and there is a unfavorable correlation between circulating soluble tumour necrosis factor receptors (TNFR) and nutritional status in these patients[5]. The driver of the cytokine activation remains uncertain but it seems likely that increased intestinal mucosal permeability in AIDS[6] allows translocation of bacteria or bacterial products into the portal vein, leading to Kupffer cell activation and release of IL-1 and TNF[7]. Translocation into the lymphatic system or peritoneum can also occur[8]. Alternatively, HIV-driven macrophage and T cell activation may be responsible. Whatever the reason for cytokine activation, there is evidence that UV-DDB2 cytokine activation can predict outcome in AIDS patients in Europe and North America. In HAART-nave Greek patients, sIL-2R in serum predicted time to death[9]. In a multivariate analysis of Spanish patients with advanced immunosuppression who had never received protease inhibitors, TNF- independently predicted death[10]. As most previous work has been carried out in patients with less advanced disease, there is a poor understanding of predictors of outcome in patients with advanced immunosuppression, and it is in this group that most patients with diarrhoeal disease fall. Viral load does not predict Compound K outcome particularly well in this sub-group of patients[10]. We therefore decided to attempt to define cytokine predictors of mortality in African patients with diarrhoea. As previous work has tended to focus on a limited number of soluble markers, we attempted to encompass a wider range of molecules, including sTNFR (as a marker of TNF pathway activation), IL-6, IL-12, macrophage migration inhibitory factor (MIF), interferon- (IFN-) as well as C-reactive protein. We correlated concentrations of these cytokines (and the acute phase reactant) with 6-week mortality. == Methods == == Study groups == Serum samples and data were drawn from two previous studies, one a trial of nitazoxanide in AIDS-related diarrhoea[11] and one a community study of small intestinal dysfunction from which control samples were obtained[6]. All the patients in the nitazoxanide clinical trial were HIV positive and had chronic diarrhoea. We therefore obtained HIV negative and positive asymptomatic controls from the community study of small intestinal dysfunction that had participants of a similar background to those in the nitazoxanide trial. These studies were approved by the Research Ethics Committee of the University of Zambia. They were carried out before the roll-out of the expanded access HAART programme Compound K over the last.