HARC 017 - Chemokine Receptor/Ligand Polymorphisms in
HIV-1 Infection and AIDS Progression: Feasibility of Stem Cell Transplantation
of AIDS Patients with HIV-1 Resistant, HLA-Identical Related Donors.
This study, conceived by Dr. Randy Wada of the Cancer Research Center of
Hawaii, will be conducted in collaboration with HARC and RRL.
The project is pending submission to the CRC for funding and for
biostatistical assistance in determining the sample size.
Several groups have demonstrated the importance of genetic polymorphisms
of chemokine receptors and their ligands in the disease free survival of
HIV-1-infected patients. Chemokine
receptors serve as important HIV-1 entry cofactors with the CD4 molecule for
both T cell and macrophage-tropic strains of the virus.
Specific genetic mutations conferring favorable outcome or resistance to
infection have been described in the chemokine receptor 5 (CCR5D32), chemokine
receptor 2 (CCR2)64I), and SDF1-3âA chemokine. Despite the success of HAART, current medical drug
therapy is associated with the emergence of resistant HIV-1 variants.
It is theoretically possible that a stem cell transplant from an HLA-matched
sibling with these favorable genetic polymorphisms to an HIV-1-infected
individual lacking these same HIV-1-resistance chemokine receptor mutations may
lead to prolonged disease free survival. Many
of these favorable genetic variations may exist in relatively high frequency in
the mixed ethnicity present in the local population.
This study aims to obtain information about these genetic variations in
our HIV-1-infected population in Hawaii as well as to assess the potential
feasibility of such stem cell transplantation as a therapeutic modality for
HIV-1 infection.