SUMMARY Current treatment of HIV-1 infection has changed the face of the disease by converting a once acute deadly disease to a chronic illness. As such, many other issues have surfaced that require close attention including comorbidities associated with the presence of the viral genome, as well as the potential side effects of ART on several tissues and cells including brain that impact on the homeostasis of neuronal cells thus contributing to neurocognitive and behavioral disorders seen among people living with HIV (PWH). Other areas of concern relate to social and structural determinants of NeuroHIV disparities in the PWH community. Now, it has become increasingly clear that the landscape must move toward a cure by employing sophisticated, innovative, next generation approaches and technologies that are aimed at the permanent elimination of HIV-1 in PWH and protect uninfected individuals from HIV-1 infection at the cellular and molecular levels. Importantly, a parallel approach to improve neurocognitive/psychological disorders in the HIV community as well as the use of molecular strategies for elimination/protection must be implemented to end more than four decades of clinical challenges caused by HIV-1 infection. By combining resources and expertise of our teams at Temple and Drexel, we have developed a Comprehensive NeuroHIV Center (CNHC) facility to provide services to scientists from the greater Philadelphia area and beyond to initiate and investigate the current issues associated with neuroscience of HIV-1 from community to laboratory and clinic with an emphasis on neuropsychiatric/behavioral (a new area of emphasis), continued studies on the neuroscience of HIV-1 infection, and the development of cure strategies at the molecular and cellular levels by the elimination of HIV-1 proviral DNA from the host using a genetic approach such as CRISPR gene editing-based technologies. We propose that this unique and unprecedented strategy will have dual benefit in improving current challenges associated with HIV-1 infection in PWH community and offer new opportunities for the development of a novel approach for mitigation/elimination of viral infection by a highly collaborative and complementary group of scientists. Our goals remain to provide neuroHIV research infrastructure and support utilizing and expanding the CNHC's rich clinical neuropsychological data from a longitudinal cohort of PWH, including primarily Black/African-American and White participants that identify as non-Hispanic or Hispanic origin well-characterized by deep sequencing and detailed immunophenotyping as described in the Clinical and Translational Research Support Core (CTRSC), working closely with NeuroHIV Community Partnership and Disparities Core (NHCPDC) and taking advantage of the expert services offered by Viral Gene Editing and Bioinformatics Core (VGEBC), together with resources offered by the Cell Biology and Functional Analysis Core (CBFAC), and the financial and in...