title: Lack of immunotoxicity of saquinavir (Ro 31-8959) used alone or in double or triple combination with AZT and ddC.
abstract: Saquinavir (Ro 31-8959; SQV) has been demonstrated to be a potent inhibitor of human immunodeficiency virus (HIV) proteinases and acts synergistically with dideoxynucleoside analogues. The aim of this study was to investigate the in vitro immunomodulatory effects of SQV on normal human peripheral blood mononuclear cells (PBMC) and on lamina propria mononuclear cells (LPMC). We used the drug either alone or in double and triple combination with AZT and ddC to assess whether SQV enhances the immunomodulatory effects induced by AZT and ddC that we previously observed. We demonstrated that SQV did not induce any modulation of the proliferative response either in PBMC or in LPMC. Similarly, NK cell-mediated cytotoxic activity and cytokine production were not modified by SQV. More importantly, SQV/AZT, SQV/ddC, and SQV/AZT/ddC combinations did not strengthen neither the inhibition of PBMC and LPMC proliferative response or the modulation of cytokine production induced by AZT, ddC, and AZT/ddC. On the other hand, the increased IL-2 production induced by AZT and ddC was not observed adding SQV to the dideoxynucleoside analogues. In conclusion, we demonstrated that SQV used in combination with AZT and ddC did not add any further immunotoxicity.
authors.affiliation: Immunology Department, Istituto Superiore di Sanità, Roma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Viora
authors.forename: G
authors.initials: G
authors.lastname: Di Genova
authors.forename: M G
authors.initials: MG
authors.lastname: Quaranta
authors.forename: M
authors.initials: M
authors.lastname: Boirivant
authors.forename: B
authors.initials: B
authors.lastname: Camponeschi
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003603:Cytotoxins / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D006801:Humans; D007422:Intestines / Q000166:cytology; D007694:Killer Cells, Natural / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019258:Saquinavir / Q000494:pharmacology*; D016047:Zalcitabine / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D003603:Cytotoxins; D004338:Drug Combinations; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015215:Zidovudine; D016047:Zalcitabine; D019258:Saquinavir