Table S1 Concentration ranges (mg/mL) of each drug tested in double and triple combinations against different influenza A viruses. Drugs were titrated at half log 10 Figure S1 Synergy plot of double and triple combinations of amantadine, ribavirin, and oseltamivir carboxylate against 2009 H1N1 A/California/05/09 (CA05) replication as determined by Neutral Red assay in MDCK cells. Calculated additive interactions were subtracted from the experimentally determined inhibition to reveal regions of synergy (inhibition above expected) or antagonism (inhibition below expected). Values were derived from mean triplicate data and presented at 95% confidence. This experiment was repeated a total of six times with similar results. Blue areas indicate concentrations of each drug that are synergistic, gray areas indicate concentrations that are additive, and red areas indicate concentrations that are antagonistic. The intensity of the color (blue or red) corresponds to percent inhibition above or below expected. Figure S4 Viability of MDCK cells treated with the TCAD regimen. MDCK cells were incubated with the TCAD regimen at the highest concentrations of all three drugs used in the synergy experiments (3.2 mg/mL amantadine, 10 mg/mL ribavirin, and 3.2 mg/mL oseltamivir carboxylate), and cell viability was determined by Neutral Red assay after 72 hours. Values are the mean of nine replicates from three experiments, with standard deviations. The difference in viability between the TCAD treated cells and the cell controls was not statistically significant (P = 0.47, Student's t-test). Found at: doi:10.1371/journal.pone.0009332.s006 (1.00 MB TIF) Successful treatment of HIV-associated multicentric Castleman's disease and multiple organ failure with rituximab and supportive care: a case report INTRODUCTION: Multicentric Castleman's Disease (MCD), a lymphoproliferative disorder associated with Human Herpes Virus-8 (HHV-8) infection, is increasing in incidence amongst HIV patients. This condition is associated with lymphadenopathy, polyclonal gammopathy, hepato-splenomegaly and systemic symptoms. A number of small studies have demonstrated the efficacy of the anti-CD20 monoclonal antibody, rituximab, in treating this condition. CASE PRESENTATION: We report the case of a 46 year old Zambian woman who presented with pyrexia, diarrhoea and vomiting, confusion, lymphadenopathy, and renal failure. She rapidly developed multiple organ failure following the initiation of treatment of MCD with rituximab. Following admission to intensive care (ICU), she received prompt multi-organ support. After 21 days on the ICU she returned to the haematology medical ward, and was discharged in remission from her disease after 149 days in hospital. CONCLUSION: Rituximab, the efficacy of which has thus far been examined predominantly in patients outside the ICU, in conjunction with extensive organ support was effective treatment for MCD with associated multiple organ failure. There is, to our knowledge, only one other published report of its successful use in an ICU setting, where it was combined with cyclophosphamide, adriamycin and prednisolone. Reports such as ours support the notion that critically unwell patients with HIV and haematological disease can benefit from intensive care. The spectrum of HIV-associated disease on the ICU has changed markedly since the widespread adoption of combination antiretroviral therapy (Highly Active Antiretroviral Therapy, HAART) in the late 1990s. Whilst the incidence of opportunistic infections has decreased, that of several neoplasms, including Multi-centric Castleman's Disease (MCD) and Hodgkin's lymphoma is increasing. MCD is a lympho-proliferative disorder associated with Human Herpes Virus-8 (HHV-8) infection, characterised by fever, lethargy, anaemia and lymphadenopathy. Lymph node histology typically reveals angiofollicular hyperplasia and plasma cell infiltration. There is as yet no accepted therapeutic gold standard for MCD. Initial treatment approaches involved chemotherapy with agents such as vinblastine, etoposide and doxorubicin plus corticosteroids. More recently the anti-CD20 monoclonal antibody, rituximab, has been used. This targets HHV-8-infected plasmablasts, which coexpress the B cell antigen CD20. Small case series of patients with MCD have shown rituximab to be an effective therapy in patients that do not require organ support on the intensive care unit [1] [2] [3] .