Structural brain changes associated with detectable HIV DNA

M.S. University of Hawaii at Manoa 2012.Includes bibliographical references.In the era of potent antiretroviral therapy, HIV-related neurocognitive dysfunction remains prevalent although its severest form, HIV dementia, has become less common. Patients with well-controlled infection often continue to experience neurologic and cognitive impairment. HIV neuropathogenesis is incompletely understood. The persistence of cognitive dysfunction in HIV may be secondary to HIV-infected peripheral blood mononuclear cells which cross the blood-brain barrier, eventually causing perivascular inflammation and neuronal injury. Optimal antiretroviral therapy can reduce HIV RNA in plasma to undetectable levels while failing to eradicate the virus from cellular reservoirs. Circulating proviral HIV DNA in peripheral blood cells is known to correlate with HIV-related cognitive deficits. Although altered brain structure has been linked to HIV-associated neurocognitive disorders, the relationship of HIV DNA to brain structure has not been previously examined. This thesis, in a study of antiretroviral-treated HIV-infected individuals with suppressed plasma HIV RNA, relates brain regional volumes and cortical thickness to HIV DNA in peripheral blood mononuclear cells. Identifying the association between this latent viral reservoir and structural brain changes may help to determine the neuropathogenesis of HIV infection, with possible implications for disease management and development of new therapies