Effects of Protease Inhibiton and Proteasome, Soluble Interleukin-2-Receptor (sIL-2R) in Biclonal Gammopathy-Human Immunodeficiency Virus Patients (BG-HIV).

Human immunodeficiency virus-1 (HIV-1) encodes for a protease required for the cleavage of the viral gag-pol polyprotein. HIV-1 protease inhibition (PI) has revolutionized HIV therapy. Recently the 20S proteasome has been shown to cleave the same sites as PI, therefore proteasome inhibition may contribute to some of the effects of PI independent of virus inhibition. Tumor cells of multiple myeloma have been shown to be heavily dependent proteasome regulated proteins for their growth and interaction with stromal cells. Nuclear factor-kb (NF-kb) a transcription factor is an important promoter of myeloma cell growth within bone marrow microenvironment by upregulating IL-6, CRP, VEGF and cell adhesion. We observe a 60+ yo female with HIV-myeloma (biclonal Gammopathy IgG- kappa, IgM-lambda with hypercoagulable state, hyperviscosity syndrome with epistaxis, CHF, fatiqueness, and HIV-1, CD4-728/cumm (22%) but a viral load > 100,000 copies/ml, M-protein IgG of 6.9g/L, IgM of >2 g/L, kappa and lambda (biclonality) respectively. C-reactive protein of 40 mg/dl. With ritonavir-based HAART over 12 weeks lead to over a 50% M-protein reduction and normalization of sIL-2R.

CONCLUSION: HIV-1 protease inhibitors-Ritonavir based therapy-HAART may modulate proteasome activity and cytokines in HIV-myeloma (biclonal gammopathy) patients independent of virus inhibition and reduce tumor mass burden with increase survival and QOL.