A defective chemokine motif in the HIV-1 Tat protein has been hypothesized to alter central nervous system cellular trafficking and inflammation, rendering HIV-1 subtype C less neuropathogenic than B. To evaluate this hypothesis, we compared biomarkers of cellular chemotaxis and inflammation in cerebrospinal fluid (CSF) and serum in individuals infected with HIV-1 subtypes B (n=27) and C (n=25) from Curitiba, Brazil. None had opportunistic infections. Chemokines (MCP-1, MIP-1α, MIP-1β, RANTES, IP-10) and cytokines (TNF-α, IFN-y, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-10) were measured using the multiplex bead suspension array immunoassays or ELISA HD. CSF and serum biomarker concentrations were compared between subtype B and C groups and HIV-positive and HIV-negative subjects (N=19) using an independent group t-test (unadjusted analysis) and linear regression (adjusted analysis), controlling for nadir CD4 and CSF and plasma HIV RNA suppression. CSF levels of cytokines and chemokines were significantly (p< 0.05) elevated in HIV-positive versus HIV-negative participants for 7/13 biomarkers measured, but levels did not differ for subtypes B and C. Serum levels were significantly elevated for 4/13 markers, with no significant differences between subtypes B and C. Although pleocytosis was much more frequent in HIV-positive than in HIV-negative individuals (27% vs. 0%), subtypes B and C did not differ (32% and 22%; p = 0.23). We did not find molecular evidence to support the hypothesis that intrathecal chemotaxis and inflammation is less in HIV-1 subtype C than in subtype B. Biomarker changes in CSF were more robust than in serum, suggesting compartmentalization of the immunological response to HIV.

IntroductionThere is an unmet need for effective methods for conducting dementia prevention trials.MethodsHome‐based assessment study compared feasibility and efficiency, ability to capture change over time using in‐home instruments, and ability to predict cognitive conversion using predefined triggers in a randomized clinical trial in (1) mail‐in questionnaire/live telephone interviews, (2) automated telephone/interactive voice recognition, and (3) internet‐based computer Kiosk technologies. Primary endpoint was defined as cognitive conversion.ResultsAnalysis followed a modified intent‐to‐treat principle. Dropout rates were low and similar across technologies but participants in Kiosk were more likely to dropout earlier. Staff resources needed were higher in Kiosk. In‐home instruments distinguished conversion and stable groups. Cognitively stable group showed improvement in cognitive measures. Triggering was associated with higher likelihood of conversion but statistically significant only in mail‐in questionnaire/live telephone interviews.DiscussionRelatively low efficiency of internet‐based assessment compared with testing by live‐assessors has implications for internet‐based recruitment and assessment efforts currently proposed for diverse populations.