A matched cross-sectional study of the association between circulating tissue factor activity, immune activation and advanced liver fibrosis in hepatitis C infection.

BACKGROUND: Tissue factor (TF) is a protein that mediates the initiation of the coagulation cascade. TF expression is increased in patients with poorly-controlled HIV, and may be associated with increased immune activation that leads to cardiovascular morbidity. The role of TF in immune activation in liver disease in hepatitis C virus (HCV)-monoinfection and HIV/HCV-coinfection has not been explored. METHODS: Fifty-nine patients were stratified: A) HIV-monoinfection (N = 15), B) HCV-monoinfection with chronic hepatitis C (CHC) (N = 15), C) HIV/HCV-coinfection with CHC (N = 14), and D) HIV/HCV-seropositive with cleared-HCV (N = 15). All HIV+ patients had undetectable HIV viremia. Whole blood was collected for CD4/CD8 immune activation markers by flow cytometry and plasma was assayed for microparticle TF (MPTF) activity. Subjects underwent transient elastography (TE) to stage liver fibrosis. Undetectable versus detectable MPTF was compared across strata using Fisher's Exact test. RESULTS: MPTF activity was more frequently detected among patients with HCV-monoinfection (40%), compared to HIV-monoinfection and HIV/HCV-seropositive with cleared HCV (7%) and HIV/HCV-coinfection with CHC (14%) (p = 0.02). Mean TE-derived liver stiffness score in kPa was higher in patients with detectable MPTF (12.4 ± 8.5) than those with undetectable MPTF (6.4 ± 3.0) (p = 0.01). Mean CD4 + HLADR+ and CD4 + CD38-HLADR+ expression were higher in those with detectable MPTF (44 ± 9.8% and 38 ± 8.7%, respectively) than those with undetectable MPTF (36 ± 11% and 31 ± 10.4% respectively) (p = 0.05 and 0.04 respectively). CONCLUSIONS: HCV-monoinfection and HIV/HCV-coinfection with CHC were associated with MPTF activity. MPTF activity is also associated with advanced liver fibrosis and with CD4 + HLADR+ immune activation.

Relationship Dynamics and Sexual Risk Reduction Strategies Among Heterosexual Young Adults: A Qualitative Study of Sexually Transmitted Infection Clinic Attendees at an Urban Chicago Health Center.

Few studies have examined risk-reduction alternatives to consistent condom use for HIV prevention among heterosexual young adults. We used qualitative methodology to explore risk reduction strategies and contextual factors influencing attempts to reduce risk in an urban, high morbidity sexually transmitted infection (STI) clinic. Focus groups were conducted October-December 2014 with heterosexually identified men (n = 13) and women (n = 20) aged 18-29 seeking STI screening at an urban clinic. Groups were audio recorded, transcribed verbatim, and analyzed for thematic content using Atlas.ti software. Quantitative information included sociodemographics, HIV/STI testing history, and 6-month sexual behaviors. Among 33 predominantly African-American participants with a median age of 22, risk-reduction strategies included monogamy agreements, selective condom use with casual and high-risk partners, and frequent HIV/STI testing, though testing was commonly used as a post-hoc reassurance after risk exposure. Many men and women used implicit risk assessment strategies due to mistrust or difficulty communicating. Concurrency was common but rarely discussed within partnerships. Despite attempts to reduce risk, monogamy agreements were often poorly adhered to and not openly discussed. Alcohol and substance use frequently interfered with safer sexual decisions. Participants were aware of HIV/STI risk and commonly practiced risk-reduction strategies, but acknowledged faulty assumptions and poor adherence. This work provides insights into risk-reduction approaches that are already used and may be strengthened as part of effective HIV/STI prevention interventions.

Transmission clustering among newly diagnosed HIV patients in Chicago, 2008 to 2011: using phylogenetics to expand knowledge of regional HIV transmission patterns.

INTRODUCTION: HIV transmission cluster analyses can inform HIV prevention efforts. We describe the first such assessment for transmission clustering among HIV patients in Chicago. METHODS: We performed transmission cluster analyses using HIV pol sequences from newly diagnosed patients presenting to Chicago's largest HIV clinic between 2008 and 2011. We compared sequences through progressive pairwise alignment, using neighbor joining to construct an unrooted phylogenetic tree. We defined clusters as >2 sequences among which each sequence had at least 1 partner within a genetic distance of ≤1.5%. We used multivariable regression to examine factors associated with clustering and used geospatial analysis to assess geographic proximity of phylogenetically clustered patients. RESULTS: We compared sequences from 920 patients, median age of 35 years, 75% male, 67% black, 23% Hispanic, and 8% had a rapid plasma reagin titer ≥1:16 concurrent with their HIV diagnosis. We had HIV transmission risk data for 54%; 43% identified as men who have sex with men (MSM). Phylogenetic analysis demonstrated 123 patients (13%) grouped into 26 clusters, the largest having 20 members. In multivariable regression, age <25, black race, MSM status, male gender, higher HIV viral load, and rapid plasma reagin ≥1:16 associated with clustering. We did not observe geographic grouping of genetically clustered patients. DISCUSSION: Our results demonstrate high rates of HIV transmission clustering, without local geographic foci, among young black MSM in Chicago. Applied prospectively, phylogenetic analyses could guide prevention efforts and help break the cycle of transmission.

Characterization of CD4⁺ T-cell immune activation and interleukin 10 levels among HIV, hepatitis C virus, and HIV/HCV-coinfected patients.

BACKGROUND: HIV/hepatitis C virus (HCV)-coinfected patients have accelerated liver disease compared with HCV monoinfection. In HIV-positive patients with viral suppression, data comparing inflammatory cytokines and immune activation between HIV/HCV coinfection with chronic hepatitis C (CHC) to HIV/HCV-seropositive patients with cleared HCV are limited. METHODS: Fifty-nine age- and sex-matched patients were stratified: (1) HIV monoinfection (n = 15); (2) HCV monoinfection with CHC (n = 15); (3) HIV/HCV coinfection with CHC (n = 14); and (4) HIV/HCV seropositive with cleared HCV (n = 15). All HIV-positive patients had undetectable HIV viremia, and median CD4 was 420 cells per microliter. Liver fibrosis was assessed in each subject using transient elastography. Cells were collected for CD4 and CD8 immune activation (CD38/HLA-DR) markers via flow cytometry and plasma for luminex-multiplex cytokine assays. RESULTS: CD38⁺HLA-DR⁺ expression on CD4⁺ T cells was significantly increased in HIV/HCV coinfection with CHC (7%) versus HCV monoinfection (4%) (P = 0.012). CD4⁺ total HLA-DR⁺ expression was significantly increased in HIV/HCV coinfection with CHC (43%) versus HIV monoinfection (31%) (P = 0.010) and HIV/HCV seropositive with cleared HCV (38%) (P = 0.046). Total CD4⁺CD38⁺ and CD4⁺CD38⁺HLA-DR⁻ expression was significantly higher in HIV monoinfection (23% and 18%) than HCV moninfection (13%, P = 0.002% and 9%, P = 0.001, respectively). Interleukin 10 levels were significantly lower in HIV monoinfection versus HIV/HCV coinfection with CHC (P = 0.0002). In multivariate analysis, severe fibrosis was associated with lower expression of CD4⁺CD38⁺HLA-DR⁺ and CD4⁺ total CD38⁺ than mild-moderate fibrosis (P = 0.03 and 0.03, respectively). CONCLUSIONS: CD4 immune activation with HLA-DR⁺ expression in HIV/HCV coinfection with well-controlled HIV may arise from chronic HCV viremia. Conversely, CD4⁺CD38⁺ expression may be driven by underlying HIV infection. CD4 immune activation was unexpectedly found to be associated with decreased liver fibrosis.