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Brain vascular intima vulnerability among HIV-positive and negative individuals.

ABSTRACT: OBJECTIVE:To test whether HIV is associated with brain large artery vulnerable intima. DESIGN:Cross-sectional study of autopsied HIV-positive (HIV+) cases sex and age-matched to HIV-negative (HIV-) controls. METHODS:Brain large arteries from 302 autopsied cases (50% HIV+) were evaluated morphometrically for the presence of atherosclerosis, size of necrotic core, and fibrous cap thickness. Intima vulnerability was measured as intima elastolytic score [0-5, based on intimal metalloproteinases (MMP)-2, MMP-3, and MMP-9, and tissue inhibitor for MMP-1 and MMP-2 staining], intima inflammatory score (0-3, based on intimal presence of CD3 and CD68 cells and TNF-? staining), neoangiogenesis (factor VIII staining), and apoptosis (caspase 3 staining). Hierarchical generalized linear models were used to obtain the beta estimates and their 95% confidence intervals, adjusting for demographics and vascular risk factors. RESULTS:The prevalence of atherosclerosis did not differ by HIV status. Necrotic cores filled larger proportions of the intima in HIV+ individuals with CD4 cell count above 200?cells/?l at death compared to HIV- controls (adjusted B?=?11.6%, P?=?0.04). HIV+ individuals had greater elastolytic scores (adjusted B?=?0.34, P?=?0.02), especially those with less than 200 CD4 cells/?l at death (adjusted B?=?0.41, P?=?0.01). Intima inflammation, neoangiogenesis, and apoptosis were not different among HIV+ cases versus HIV- controls. CONCLUSION:Individuals with HIV and CD4 cell count at least 200?cells/?l at death had relatively larger necrotic cores, whereas those with HIV and CD4 cell count below 200?cells/?l at death had evidence of increased connective tissue remodeling in the intima. These findings suggest an increased potential for endothelial erosion, thrombosis, and plaque rupture that may relate to higher risk for vascular events.

SUBMITTER: Hunter MD

PROVIDER: S-EPMC6136984 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Brain vascular intima vulnerability among HIV-positive and negative individuals.

Hunter Madeleine D MD Shenoy Adele A Dwork Andrew A Elkind Mitchell S V MSV Marshall Randolph R Mohr Jay P JP Morgello Susan S Gutierrez Jose J

AIDS (London, England) 20180901 15

<h4>Objective</h4>To test whether HIV is associated with brain large artery vulnerable intima.<h4>Design</h4>Cross-sectional study of autopsied HIV-positive (HIV+) cases sex and age-matched to HIV-negative (HIV-) controls.<h4>Methods</h4>Brain large arteries from 302 autopsied cases (50% HIV+) were evaluated morphometrically for the presence of atherosclerosis, size of necrotic core, and fibrous cap thickness. Intima vulnerability was measured as intima elastolytic score [0-5, based on intimal m ...[more]

PMID: 30005012

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Project description:BACKGROUND:Although it has been purported that HIV-positive individuals may experience a greater degree of intoxication than HIV-negative individuals following acute alcohol consumption, no research to date has empirically tested this supposition. The present investigation entailed a randomized controlled experiment to identify whether the administration of a weight-specified dose of alcohol would lead to differential blood alcohol concentrations (BACs) among HIV-positive versus HIV-negative men. METHODS:In a specialized barroom laboratory, 143 men (n = 76 HIV-positive and n = 67 HIV-negative; mean age = 42.9) consumed beverages based on a formulation of 0.7 g alcohol/kg body weight over a 15-minute time frame. BAC was assessed via breathalyzer at 2 set time points (10 and 13 minutes postconsumption) and then periodically until detoxification (BAC < 0.040%). Primary outcomes included (i) area under the curve (AUC), calculated based on all of one's BAC readings, (ii) "BAC-EXP," defined as one's BAC reading 13 minutes postconsumption, and (iii) BAC-PEAK, defined as one's highest recorded BAC reading. RESULTS:Contrary to predictions, AUC (t(141) = 2.23, p = 0.027), BAC-EXP (t(141) = 2.68, p = 0.008), and BAC-PEAK (t(141) = 2.29, p = 0.023) were significantly lower among HIV-positive versus HIV-negative participants. These effects were sustained in multivariable models controlling for age, race, and AUDIT-based hazardous drinking classification. Among the HIV-positive sample, outcomes did not significantly differ based on HIV viral load detectability, antiretroviral therapy (ART) status, or ART adherence. CONCLUSIONS:The administration of a controlled, weight-specified dose of alcohol led to lower BACs among HIV-positive versus HIV-negative participants. These differences might derive from decreased body fat percentage and delayed gastric emptying associated with HIV seropositivity; however, additional research is necessary to verify these mechanisms. Unique alcohol dosing formulas based on HIV serostatus may be required in future alcohol administration experiments involving HIV-positive samples.

Project description:BackgroundHigh dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population.MethodsWe conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10-15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor.ResultsThe median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and non-dipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001).ConclusionsThe results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this.

Project description:ImportanceDespite the introduction of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders continue to be a problem for treated HIV-positive individuals. The cause of this impairment remains unclear.ObjectiveTo determine if detectable brain changes occur during a 2-year period in HIV-positive individuals who were aviremic and treated with cART.Design, setting, and participantsIn this longitudinal case-control study, participants underwent neuroimaging and neuropsychological assessment approximately 2 years apart. Data were collected from October 26, 2011, to March 1, 2016. Data from 92 HIV-positive individuals were acquired at Washington University in St Louis from ongoing studies conducted in the infectious disease clinic and AIDS Clinical Trial Unit. A total of 55 HIV-negative control participants were recruited from the St Louis community and a research participant registry. A total of 48 HIV-positive individuals who were aviremic and treated with cART and 31 demographically similar HIV-negative controls met the study requirements and were included in the analyses.Main outcomes and measuresBrain volumes were extracted with tensor-based and voxel-based morphometry and cortical modeling. Raw scores from neuropsychological tests quantified cognitive performance. Multivariable mixed-effects models assessed the effect of HIV serostatus on brain volumes and cognitive performance, and determined if HIV serostatus affected how these measures changed over time. With HIV-positive participants, linear regression models tested whether brain volumes and cognitive performance were associated with measures of infection severity and duration of infection.ResultsThe 2 groups were demographically similar (HIV-positive group: 23 women and 25 men; mean [SD] age, 47.7 [13.2] years; mean [SD] educational level, 13.3 [3.4] years; and HIV-negative group, 16 women and 15 men; mean [SD] age, 51.2 [12.9] years; mean [SD] educational level, 14.5 [2.1] years). The HIV-positive participants had poorer neuropsychological test scores compared with controls on the Trail Making Test Part A (5.9 seconds; 95% CI, 1.5-10.3; P?=?.01), Trail Making Test Part B (27.3 seconds; 95% CI, 15.0-39.6; P?<?.001), Digit Symbol Substitution Task (-12.5 marks; 95% CI, -18.9 to -6.0; P?<?.001), Letter-Number Sequencing (-2.5 marks; 95% CI, -3.7 to -1.3; P?<?.001), Letter Fluency (-6.6 words; 95% CI, -11.5 to -1.6; P?=?.01), and Hopkins Verbal Learning Test-Revised immediate recall (-2.4 words; 95% CI, -4.4 to -0.4; P?=?.05), after adjusting for age, sex, and educational level. Only changes in Trail Making Test Part A significantly differed between the groups. Cortical thickness and subcortical volumes were smaller in HIV-positive individuals compared with controls. However, changes in brain volume over time were similar between the groups.Conclusions and relevanceThese findings are consistent with the idea that cognitive and structural brain changes may occur early after seroconversion, and argue that maintaining aviremia with cART can prevent or minimize progressive brain injury.

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Brain vascular intima vulnerability among HIV-positive and negative individuals.

Publications

Brain vascular intima vulnerability among HIV-positive and negative individuals.

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