Objective: To identify patient and physician characteristics that may act as determinants of adherence to prescription refill of triple combination antiretroviral therapy. Methods: A population-based analysis of antiretroviral therapy-naive HIV-positive men and women in British Columbia, Canada, who initiated triple combination therapy between August 1 1996 and October 31 1998. Study participants were considered adherent if they were actually dispensed antiretrovirals ≥95% over the first year of therapy. Log-binomial regression was used to identify patient and physician characteristics associated with adherence to prescription refill. Results: Of the 886 individuals eligible for analysis, 495 (56%) were ≥95% adherent to prescription refill. In multivariate analysis, adherence was positively associated with increased age [adjusted relative rate (ARR) 1.19; 95% CI: 1.07–1.32], having a diagnosis of AIDS (ARR 1.66; 95% CI: 1.29–2.15), being male (ARR 1.79; 95% CI: 1.27–2.53), and with greater experience of the treating physician (ARR 1.27; 95% CI: 1.13–1.42). History of injection drug use was negatively associated with adherence to prescription refill (ARR 0.65; 95% CI: 0.51–0.83), as was increased pill burden (per pill daily) (ARR 0.95; 95% CI: 0.92–0.99). A sub-analysis of 316 patients who provided additional data regarding psychosocial characteristics indicated that adherence was positively associated with physician experience (ARR: 1.28; 95% CI: 1.09–1.51) and being employed (ARR: 1.55; 95% CI: 1.14–2.21), and negatively associated with a history of injection drug use (ARR: 0.61; 95% CI: 0.43–0.85). Conclusion: While patient disease stage and personal characteristics may play an important role in patient adherence to prescription refill of complex therapeutic regimens, our findings indicate that HIV-experienced physicians may have greater success in maintaining patients on prescribed therapy.

The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac109 core gene has been previously characterized as an essential late gene. Our results showed that budded virions could be detected in supernatants of infected Sf-9 cells, even when ac109 knockout viruses displayed a single-cell infection phenotype. Moreover, confocal microscopy analysis revealed that budded virions can enter the cytoplasm but are unable to enter the cell nucleus. This defect could be repaired by complementing ac109 in trans. In addition, polyhedra of normal size could be detected in Sf-9 nuclei infected with ac109 knockout viruses. However, electron microscopy demonstrated that these occlusion bodies were empty. Altogether, these results indicate that ac109 is required for infectivity of both phenotypes of virus.

Baculoviruses are nonpathogenic viruses that infect mammals, which, among other applications, are used as vehicles for gene delivery. Here, we demonstrated that the cytosolic DNA sensor cGAS recognizes baculoviral DNA and that the cGAS-STING axis is primarily responsible for the attenuation of transduction in human and mouse cell lines through type I and type III IFNs. Furthermore, we identified DNA-dependent protein kinase (DNA-PK) as a cGAS-independent and alternative DNA cytosolic sensor that contributes less to the antiviral state in baculovirus infection in human epithelial cells than cGAS. Knowledge of the pathways involved in the response of mammalian cells to baculovirus infection will improve the use of this vector as a tool for gene therapy.