HIV DNA and cognition in a Thai longitudinal HAART initiation cohort: the SEARCH 001 Cohort Study.

HIV remains a common cause of dementia internationally while the frequency and severity in countries with broad access to highly active antiretroviral therapy (HAART) has decreased substantially.1 Early data suggest a failure of HAART to universally eradicate neurocognitive impairment (NCI) in patient populations with access to these treatments.1–5 Yet controversy exists as to whether continued cognitive impairment following HAART represents an active process, the impact of comorbidities, or pre-HAART brain injury. In its pure, untreated form, HIV encephalitis is characterized by CNS immune activation with perivascular macrophage accumulation.6 It is theorized that CNS injury occurs when monocytes, many of which are infected, transmigrate the blood–brain barrier, resulting in an inflammatory response in the absence of substantial neuronal apoptosis.7–10 This pathway has been described in animal models of lentivirus infection.11,12 In some animal models, monocyte tissue transmigration appears to trigger gene expression of otherwise quiescent virus, raising the possibility that harboring virus in peripheral monocytes, even when not actively productive, may have clinical consequences upon tissue infiltration.13 In this prospective study, we evaluated early immunologic, virologic, and neurocognitive changes with initiation of first-time HAART to clarify the neuropathogenesis of NCI in HAART-treated individuals. We previously reported a correlation between peripheral blood mononuclear cell (PBMC) HIV DNA and NCI in HAART-naive patients from this cohort.14 We now identify this relationship specific to circulating monocytes (CD14+ cells) and describe the longitudinal relationship between this marker and cognitive recovery.