PubMed · 2277993
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P Scherer. [AIDS attacks the brain].. https://pubmed.ncbi.nlm.nih.gov/2277993/
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OBJECTIVE: To determine changes in CD14/CD69 cells of HIV seropositive patients with HIV-1 associated dementia (HAD) on highly active antiretroviral therapy (HAART) and to determine the effect of soluble factors from cultured monocyte/macrophage (M/M phi) on neural cell functional proteins. DESIGN AND METHODS: Whole blood from patients with HAD, HIV seronegative subjects, and HIV seropositive subjects with no dementia (HIV-ND) was analyzed for CD14/CD69 cells using flow cytometry. M/M phi were isolated and cultured, and supernatants tested for neurotoxicity. Modulation of neural cell proteins and mitogen-activated protein kinases in response to supernatant exposure was examined by Western blot. RESULTS: CD14/CD69 levels from HAART-treated HAD subjects were significantly elevated over those from HIV-ND subjects and controls. However, levels were significantly lower than those reported in similarly selected HAD subjects tested prior to the HAART era. Treatment of neural cells with M/M phi-derived culture supernatants from HAART-treated HAD subjects was not associated with cell death, but resulted in a trend towards lower activation of the JNK, AKT, and ERK kinases, decreased expression of SNAP-25, and increased expression of neurofilament light than was observed after treatment with HIV-ND M/M phi supernatants. CONCLUSIONS: The clinical phenotype of HAD appears to be evolving from a subacute dementing disease to a more protracted disorder. Decreased CD14/CD69 levels may reflect changes in some aspects of the pathophysiology of brain injury in the era of HAART. Changes in neural cell signaling, structural and functional proteins may represent more subtle neurotoxicity, manifested in cell dysfunction rather than frank cell death.
OBJECTIVE: To examine the association between Kaposi's sarcoma (KS), human herpes virus 8 (HHV8) and AIDS dementia complex (ADC). DESIGN: A total of 599 HIV-1 infected homosexual men participated in a prospective cohort study (Amsterdam, 1984-1996). METHODS: The risk for ADC in patients with prior KS or HHV8 infection was estimated using the Cox proportional hazards method with adjustments for antiretroviral medication and low CD4 cell counts. RESULTS: Of the 599 participants, 290 (48.4%) had HHV8 antibodies, 99 (16.5%) had KS and 30 (5.0%) had ADC. ADC was diagnosed in 5.2% of participants with KS and 5.0% of those without KS, and in 4.8% of HHV8 seropositive compared to 5.2% seronegative individuals and thus was not associated with KS or HHV8 infection. Using a time-dependent Cox proportional hazards analysis with the date of KS as risk factor, the risk for ADC was 2.7 [95% confidence interval (CI), 0.92-7.96; P = 0.07) and when only definite ADC was considered it was 3.5 (95% CI, 1.00-12.26;P = 0.05). After adjusting for decreases in CD4 cell count and use of medication, the hazards ratio for participants with KS to develop ADC was 2.0 (95% CI, 0.66-5.77; P = 0.23) and 2.6 (95% CI, 0.73-9.12; P = 0.14), respectively. HHV8 seropositivity, adjusted for the same variables, showed a risk for ADC of 0.85 (95% CI, 0.41-1.77;P = 0.66) and for definite ADC 0.69 (95% CI, 0.27-1.73; P = 0.42). The expected neuroprotective effects of antiretroviral medication were observed. CONCLUSIONS: KS or HHV8 does not significantly influence the risk for developing ADC in a group with a uniform risk for developing KS therefore we recommend caution in searching for a KS-associated or HHV8-derived therapy for ADC.
Cellular immunity against human immunodeficiency virus type 1 (HIV-1)-infected brain macrophages serves to prevent productive viral replication in the nervous system. Inevitably, during advanced disease, this antiretroviral response breaks down. This could occur through virus-induced dysregulation of lymphocyte trafficking. Thus, we studied the production of non-ELR-containing alpha-chemokines and their receptor (CXCR3) expression in relevant virus target cells. Macrophages, lymphocytes, and astrocytes secreted alpha-chemokines after HIV-1 infection and/or immune activation. Lymphocyte CXCR3-mediated chemotactic responses were operative. In all, alpha-chemokine-mediated T cell migration continued after HIV-1 infection and the neuroinflammatory events operative during productive viral replication in brain.