Stress Biomarkers as Outcomes for HIV+ Prevention: Participation, Feasibility and Findings Among HIV+ Latina and African American Mothers

Mothers living with HIV (MLH) are at high risk for acute and chronic stress, given challenges related to their HIV status, ethnicity, economic and urban living conditions. Biomarkers combined into a composite index show promise in quantifying psychosocial stress in healthy people, but have not yet been examined among MLH. According, we examined potential biomarker correlates of stress [cortisol and catecholamines from home-collected urine and basic health indicators (blood pressure, height and weight, waist-to-hip ratio) measured during an interview] among 100 poor African American and Latina mothers MLH and demographic-matched control mothers without HIV (n = 50). Participants had been enrolled in a randomized controlled trial about 18 months earlier and had either received (MLH-I) or were awaiting (MLH-W) the psychosocial intervention. Participation was high, biomarkers were correctly collected for 93% of cases, and a complete composite biomarker index (CBI) calculated for 133 mothers (mean age = 42). As predicted, MLH had a significantly higher CBI than controls, but there was no CBI difference across ethnicity or intervention group. CBI predicted CD4 counts independently after controlling for age, years since diagnosis, prior CD4 counts, medication adherence, and depression symptoms. The study demonstrates acceptability, feasibility and potential utility of community-based biomarker collections in evaluating individual differences in psychosocial stress

CXCL10 induces the recruitment of monocyte‐derived macrophages into kidney, which aggravate puromycin aminonucleoside nephrosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111251/1/cei12579.pd

Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment Among HIV-infected Individuals

Objective: Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals. Methods: In a cross-sectional analysis, concentrations of neopterin (NEO), tumor necrosis factor-alpha, TRP, KYN, KYN/TRP ratio, phenylalanine (PHE), tyrosine (TYR), PHE/TYR ratio, and nitrite were assessed in the cerebrospinal fluid (CSF) and plasma of HIV+ (n = 91) and HIV-negative (HIV-) individuals (n = 66). CI and MDD were assessed via a comprehensive neuropsychological test battery. A Global Deficit Score $0.5 was defined as CI. Nonparametric statistical analyses included Kruskal–Wallis and Mann–Whitney U tests, and multivariate logistic regression. Results: Following Bonferroni correction, NEO concentrations were found to be greater in CSF and TRP concentration was found to be lower in the plasma of HIV+ versus HIV- individuals, including a subgroup of aviremic (defined as HIV-1 RNA ,50 cps/mL) HIV+ participants receiving antiretroviral therapy (n = 44). There was a nonsignificant trend toward higher KYN/TRP ratios in plasma in the HIV+ group (P = 0.027; Bonferroni corrected α = 0.0027). In a logistic regression model, lower KYN/TRP ratios in plasma were associated with CI and MDD in the overall HIV+ group (P = 0.038 and P = 0.063, respectively) and the aviremic subgroup (P = 0.066 and P = 0.027, respectively), though this observation was not statistically significant following Bonferroni correction (Bonferroni corrected α = 0.0031). Conclusions: We observed a trend toward lower KYN/TRP ratios in aviremic HIV+ patients with CI and MDD

Plasma adenosine deaminase activity among HIV1 Clade C seropositives: relation to CD4 T cell population and antiretroviral therapy

Background Plasma adenosine deaminase and its isoenzymes(s) activities have been used as diagnostic marker for intracellular parasitism, including HIV infection, and malignancy of immune cells. HIV infection being primarily targeted against CD4 cells, it would be of interest to relate the activity of total plasma ADA and isoenzymes fractions to immune status and antiretroviral therapy. Methods In the present study, plasma total ADA activity (ADA<SUB>T</SUB>) including ADA<SUB>1</SUB> and ADA<SUB>2</SUB> isoenzyme(s) were assayed among HIV seropositive Clade C (n = 90) comprising both asymptomatic (n = 71) and symptomatic (n = 19) and compared with that of HIV seronegatives (n = 35). Results A significant increase in the activity of ADA<SUB>T</SUB> (16.30 ± 0.80 v/s 6.18 ± 0.30) as well as ADA<SUB>1</SUB> (6.50 ± 0.42 v/s 2.34 ± 0.16) and ADA<SUB>2</SUB> (9.79 ± 0.53 v/s 3.85 ± 0.23) isoenzyme(s) among the asymptomatic as well as the symptomatic subjects as compared to respective controls was noted. Increase in plasma ADA<SUB>T</SUB> activity, including ADA<SUB>1</SUB> and ADA<SUB>2</SUB> isoenzyme(s), were found to have negative correlation with CD4 counts (r, - 0.273; p &lt; 0.05). The increased plasma ADAT activity among the asymptomatic HIV seropositive with CD4 counts &gt; 500 (13.2 ± 1.65; p &lt; 0.01) as well as those who were on antiretroviral therapy (19.31 ± 1.36; p &lt; 0.001) was evident. Conclusions These findings suggest that plasma ADA can be a sensitive marker of an ongoing biological insult to host tissues either because of infection and/or side effects of medication. Measurement of plasma ADA activity, along with serological evidence for HIV infection may provide an alternate laboratory tool to monitor intracellular parasitism including secondary infection vis a vis the after effects of therapeutic outcome