Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C-Coinfected Persons.

BACKGROUND: Liver diseases progress faster in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV-coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). METHODS: Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction-positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. RESULTS: A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%). CONCLUSIONS: Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV-coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used.

Preventable mortality among sexual minority Canadians.

Background: Epidemiologic studies point to multiple health inequities among sexual minority people, but few studies have examined mortality. Some causes of death are more preventable than others, and access to prevention is theorized to follow patterns of access to social and material resources. The objective of this study is to compare estimates of preventable mortality between sexual minority (SM)-i.e., bisexual, lesbian, gay-and heterosexual adults in Canada. Methods: A population-based retrospective cohort with 442,260 (unweighted N) Canadian adults, ages 18-59 years, was drawn from the Canadian Community Health Survey/Canadian Mortality Database linked database (2003-2017). The Rutstein preventability rating index was used to classify cause-specific mortality (low/high). Longitudinal analyses were conducted using Cox proportional hazards models. Results: SM respondents had higher hazard of all-cause mortality (unadjusted hazard ratio [uHR] 1.28, 95% CI 1.06, 1.55). The uHR increased when the outcome was limited to highly-preventable causes of mortality (uHR 1.43, 95% CI 1.14, 1.80). The uHR further increased in sensitivity analyses using higher thresholds of the Rutstein index. SM respondents had higher hazard of cause-specific mortality for heart disease (uHR 1.53, 95% CI 1.03, 2.29), accidents (uHR 1.97, 95% CI 1.01, 3.86), HIV (uHR 75.69, 95% CI 18.77, 305.20), and suicide (uHR 2.22, 95% CI 0.93, 5.30) but not for cancer (uHR 0.86, 95% CI 0.60, 1.25). The adjusted HR (aHR) for highly-preventable mortality was not attenuated by adjustment for confounders (aHR 1.57, 95% CI 1.20, 2.05) but was reduced by adjustment for hypothesized mediators relating to access to social and material resources (marital status, children, income, education; aHR 1.11, 95% CI 0.78, 1.58). Conclusions: Preventable mortality was elevated for SM Canadians compared to heterosexuals. Early and broad access to sexual minority-affirming primary and preventive healthcare should be expanded.

The tripeptide FEG ameliorates systemic inflammatory responses to rat intestinal anaphylaxis.

BACKGROUND: Food allergies are generally associated with gastrointestinal upset, but in many patients systemic reactions occur. However, the systemic effects of food allergies are poorly understood in experimental animals, which also offer the opportunity to explore the actions of anti-allergic drugs. The tripeptide D-phenylalanine-D-glutamate-Glycine (feG), which potentially alleviates the symptoms of systemic anaphylactic reactions, was tested to determine if it also reduced systemic inflammatory responses provoked by a gastric allergic reaction. RESULTS: Optimal inhibition of intestinal anaphylaxis was obtained when 100 microg/kg of feG was given 20 min before the rats were challenged with antigen. The increase in total circulating neutrophils and accumulation of neutrophils in the heart, developing 3 h and 24 h, respectively, after antigen challenge were reduced by both feG and dexamethasone. Both anti-inflammatory agents reduced the increase in vascular permeability induced by antigen in the intestine and the peripheral skin (pinna), albeit with different time courses. Dexamethasone prevented increases in vascular permeability when given 12 h before antigen challenge, whereas feG was effective when given 20 min before ingestion of antigen. The tripeptide prevented the anaphylaxis induced up regulation of specific antibody binding of a cell adhesion molecule related to neutrophil activation, namely CD49d (alpha4 integrin). CONCLUSIONS: Aside from showing that intestinal anaphylaxis produces significant systemic inflammatory responses in non-intestinal tissues, our results indicate that the tripeptide feG is a potent inhibitor of extra-gastrointestinal allergic reactions preventing both acute (30 min) and chronic (3 h or greater) inflammatory responses.