IFN-free therapy is associated with restoration of type I IFN response in HIV-1 patients with acute HCV infection who achieve SVR.

Interferon (IFN)-free direct-acting antiviral agents (DAAs) have revolutionized chronic hepatitis C virus (HCV) treatment; early studies suggest excellent efficacy in acute HCV. However, changes in innate immune responses during DAA therapy for acute HCV are unknown. We studied interferon-stimulated gene (ISG) expression and related cytokines/chemokines in HIV-infected patients with acute HCV receiving sofosbuvir plus ribavirin (SOF+RBV) as part of the A5327 clinical trial. ISG expression was determined from PBMCs, and circulating cytokines/chemokines were quantified from serum from study participants. The overall sustained virologic response (SVR) was 57%; all treatment failures were due to virologic relapse. Apart from NOS2a, baseline ISG/chemokine/cytokine levels were similar irrespective of treatment outcome. Downregulation of ISGs was observed at treatment week four and end of treatment (EOT), implicating HCV in establishing elevated ISGs early during HCV infection. Levels of many of these ISGs increased at post-treatment week 12 (PTW12) in relapsers only, coinciding with recurrent HCV RNA. Eleven ISGs were differentially expressed in responders vs relapsers. On-treatment viral suppression was also associated with a reduction in IP-10, CXCL11 and MIP-1ß levels. In contrast, circulating IFN-α levels were significantly higher at EOT and PTW12 in responders vs relapsers. Upregulation of peripheral ISG expression is established early in the course of HCV infection during acute HCV infection, but did not predict subsequent treatment outcome with SOF+RBV. ISGs were downregulated during therapy and increased post-therapy in relapsers. IFN-α levels were higher in responders at EOT/PTW12, suggesting that impaired type I IFN production/secretion may contribute to relapse.

Development and Implementation of a Culturally Appropriate Education Program to Increase Cervical Cancer Screening among Maasai Women in Rural Tanzania.

Background: In Tanzania, the incidence of cervical cancer is nearly ten times that found in the US. Tanzanian women of the traditional Maasai tribe are financially and educationally marginalized and face a language barrier that reduces access to health care. While cervical cancer (CACX) screening programs are available locally, in our experience, Maasai women were less likely to use these services compared to local women of other tribal backgrounds. Objectives: A novel patient education program was designed to teach Maasai women about the natural history of cervical cancer and available screening and treatment. The program addressed the importance of preventative health and informed consent. Additionally, we sought to better understand the specific barriers Maasai women face in accessing and utilizing CACX screening services. Methods: The program used simple, scripted language translated into Maa language, the Maasai native language, with accompanying culturally appropriate 3D models. The effectiveness of the program was evaluated through pre and post-intervention surveys administered to Maasai and non-Maasai women as well as local healthcare providers, assessing knowledge of cervical cancer, screening, and treatment. Paired t-test analyses were used to analyze significance. Extensive question and answer sessions followed the education sessions from which additional barriers to screening were identified. Findings: Maasai women had minimal understanding of preventative health services prior to the intervention. While all groups showed an increase in knowledge following the education program, Maasai women demonstrated the greatest statistically significant improvement in knowledge. The proportion of Maasai women in attendance to CACX screening clinics increased by 18% after the intervention. Conclusions: Through a culturally sensitive and accessible patient education program, Maasai women gained knowledge of cervical cancer screening and treatment. This program serves as an adaptable model for other marginalized populations to increase patient understanding and informed consent, and to address issues that pertain to underutilization of health care services.