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Browsing by Author "Anderson, Albert M."
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Item Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection(Wolters Kluwer, 2020-12) Anderson, Albert M.; Jang, Jeong Hoon; Easley, Kirk A.; Fuchs, Dietmar; Gisslen, Magnus; Zetterberg, Henrik; Blennow, Kaj; Ellis, Ronald J.; Franklin, Donald; Heaton, Robert K.; Grant, Igor; Letendre, Scott L.; Biostatistics, School of Public HealthBackground: Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH). Methods: We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time. Results: At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease. Conclusion: Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.Item Fanconi Syndrome Accompanied by Renal Function Decline with Tenofovir Disoproxil Fumarate: A Prospective, Case-Control Study of Predictors and Resolution in HIV-Infected Patients(Public Library of Science, 2014-03-20) Gupta, Samir K.; Anderson, Albert M.; Ebrahimi, Ramin; Fralich, Todd; Graham, Hiba; Scharen-Guivel, Valeska; Flaherty, John F.; Fortin, Claude; Kalayjian, Robert C.; Rachlis, Anita; Wyatt, Christina M.; Medicine, School of MedicineObjective: The predictors of Fanconi syndrome (FS) accompanied by renal function decline with use of the antiretroviral tenofovir disoproxil fumarate (TDF) have not been assessed. In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described. Design: We prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl <60 mL/min in those without a known pre-TDF CrCl) in a multicenter observational study. These case participants were matched 1:2 to controls; characteristics between the two groups were compared. Case participants with known pre-TDF CrCl values were then followed over 48 weeks to assess renal recovery. Results: Nineteen cases and 37 controls were enrolled. In multivariable analysis, previous or concurrent use of lopinavir/ritonavir [OR 16.37, 95% CI (2.28, 117.68); P = 0.006] and reduced creatinine clearance prior to initiation of TDF [OR 1.44 for every 5 mL/min reduction, 95% CI (1.09, 1.92); P = 0.012; OR 19.77 for pre-TDF CrCl lower than 83 mL/min, 95% CI (2.24, 174.67); P = 0.007] were significantly associated with FS. Of the 14 cases followed for resolution, 7 (50%) achieved at least partial resolution (defined as recovering CrCl >70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation. Conclusions: FS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation.