Background: Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a “treatment as prevention” (TasP) effect. We assessed changes in primary HCV incidence ...following DAA access among people living with HIV (PLHIV). Methods: We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010–2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods. Findings: Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio IRR = 0.98; 95%CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89). Interpretation: Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030. Funding: This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902).
Training for experimental plant biologists needs to combine bioinformatics, quantitative approaches, computational biology, and training in the art of collaboration, best achieved through fully ...integrated curriculum development.
One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we ...experimented with a new approach based on the long-established phenomenon of the heat shock response. By using the green fluorescence protein as a reporter gene, it was demonstrated that expression of a heterologous gene with a heat shock protein 70 promoter could be elevated to 500-1000-fold over background by moderate hyperthermia (39 degrees C to 43 degrees C) in tissue cultured cells. The heat-induced green fluorescence protein expression was first detectable at 3 h after heating and reached a maximum at 18-24 h. The expression dropped back to baseline within 72 h. In addition, when cells were infected with adenovirus vectors containing the heat-inducible interleukin 12 or tumor necrosis factor alpha genes and then heated (42 degrees C, 30 min), expression was at least 13,600- or 6.8 x 10(5)-fold over background, respectively. Intralesion injection of the interleukin-12-carrying adenovirus vector in a mouse melanoma tumor model caused significant tumor growth delay only with hyperthermia treatment. Our results therefore support heat-induced gene expression as a feasible approach for targeted cancer gene therapy.
Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Individuals from the ...Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 ...L between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up PYFU) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/...L. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/...L among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval CI, 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/...L to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/...L. Persons with a current CD4 of 500-749 cells/...L had a significantly higher rate of ADIs (adjusted incidence rate ratio aIRR, 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/...L had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/...L. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/...L to 750-999 cells/...L. The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/...L compared to those with a CD4 count of 750-999 cells/...L, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/... (ProQuest: ... denotes formulae/symbols omitted.)
Undergraduates (n = 311) who volunteered to participate in an experiment on "Hypnotizability and Personality" filled out several personality questionnaires (including the Dissociative Experiences ...Scale; DES), were administered the Harvard Group Scale of Hypnotic Susceptibility (HGSHS), and completed a self-rating of hypnotizability. The DES overall score correlated significantly with the HGSHS summary score (r(309) = .12, p < .05, two-tailed) and with subject's self-rating of hypnotizability (r(309) = .13, p < .05, two-tailed). The magnitude of these correlations was similar to that observed in a previous study (.14 & .18) and is also similar in magnitude to the correlations typically observed between the HGSHS and the Tellegen Absorption Scale. The potential clinical implications of these findings are discussed.
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