Pathophysiology of HIV infection
Dr. Laurence is pursuing the pathophysiology of cardiovascular and skeletal abnormalities linked to HIV disease and its therapies. He has defined a mechanism for initiation of thrombotic microangiopathies such as TTP and HUS in the setting of HIV infection, related to microvascular endothelial cell apoptosis mediated by members of the tumor necrosis family of cytokines. He has documented relationships with similar thrombotic disorders in HIV negative patients. Dr. Laurence is also exploring HIV-linked loss of bone mineral density, with development of osteoporosis and enhanced fracture risk, and its paradoxical acceleration by certain anti-HIV protease inhibitors. He has demonstrated that HIV induces RANKL, the obligate cytokine for differentiation and activity of the bone-resorbing osteoclast. In addition he found that certain HIV protease inhibitors can enhance the activity of RANKL by blocking the physiologic degradation of its nuclear signaling protein, TRAF6, in the proteasome. Dr. Laurence is also leading a new clinical trial of anti-HIV anti-sense gene therapy for advanced HIV infection. He is committed to public dissemination of information about HIV/AIDS, as Editor-in-Chief of AIDS Patient Care and STDs and The AIDS Reader, and as Senior Consultant for Programs at amfAR, The Foundation for AIDS Research (amfAR).