| Publication Abstract Display | | Type: Published Abstract | | Title: Increased cerebral beta amyloid deposition in HIV positive subjects with neurocognitive impairment. | | Authors: Achim CL, Cronin MV, Buchsbaum MS, Decastro A, Fennema-Notestine C, Archibald SL, Marcotte TD, Franklin DRJ, Soontornniyomkij B, Soontornniyomkij V, Umlauf A, Ellis RJ, Heaton RK, Grant I | | Year: 2012 | | Publication: Journal of NeuroVirology | | Volume: 18 Issue: Suppl 1 Pages: S3 | | Abstract:Integrase inhibitors are a new class of promising antiretroviral drugs in our armamentarium against chronic HIV infection. They are especially valuable in long term combination treatments due to their reported low neurotoxicity. The main goal of this study was to understand the effects that Raltegravir (RAL) has on human monocyte-derived macrophage (MDM) production of immune-mediators when exposed to HIV. We compared RAL effects with that of other antiretroviral (ARV) compounds like Efavirenz (EFV) and combination therapy, including Tenofovir (TDF) and Emtricitabine (FTC). Pro-inflammatory cytokines, IFN-γ, IL-10, IL-12-p70, IL-1, IL-8, TNF-α, and IL-6 were measured simultaneously in tissue culture supernatants from primary MDM. We tested RAL alone and in combination with TDF and FTC, and compared to EFV, alone and in combination with TDF and FTC. We found that RAL treatments resulted in the lowest levels of IL-8 five days after exposure to HIV compared to the other ARV formulations. Also, at earlier time points (days 2 and 3) IFN-γ and IL-10 were lower in the formulations that included RAL. Although all the ARVs decreased TNF-α production at day 2 in MDM exposed to HIV when compared to non-ARV treated controls, each ARV combination led to increased TNF-α at day 4, with RAL alone the lowest, indicating the possibility that the EFV or TDF/FTC caused the increase. The most significant effect of RAL, both in combination and alone, was on MDM prodution of IL-8. Since IL-8 functions as a potent chemoattractant, this may be relevant in reducing overall inflammation that may further impact on blood-brain-barrier permeability. Exploring the effects of RAL on pro-inflammatory molecule production in brain macrophages may also contribute to designing ARV neuroprotective strategies in chronic HIV infection. This work was supported by NIH grant R01 MH94159 to CA, BS, and ET, and a Merck IISP grant to CA. |
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