Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a.

CD4+ T cells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat. By contrast, proviruses near H3K27ac marks were actively selected against, likely due to increased susceptibility to panobinostat. These data suggest that latency-reversing treatment can increase the immunological vulnerability of HIV-1 reservoir cells and accelerate the selection of epigenetically privileged HIV-1 proviruses.

Recovery Assessment Scale - Domains and Stages (RAS-DS): Its feasibility and outcome measurement capacity.

OBJECTIVE: A self-report instrument of mental health recovery is needed both to facilitate collaborative, recovery-oriented practice and measure recovery-focused outcomes. The Recovery Assessment Scale - Domains and Stages (RAS-DS) has been developed to simultaneously fulfill these goals. The aim of this study was to test the feasibility and measurement properties of the RAS-DS. METHOD: Feasibility was examined by 58 consumer-staff pairs volunteering from 3 non-government organisations. Consumers completed the RAS-DS, discussed it with staff, and then both completed Usefulness Questionnaires. The psychometric properties were examined using Rasch analysis with the data from these consumer participants and from additional participants recruited from two Partners in Recovery programs (N=324). RESULTS: Over 70% of consumers reported taking 15 minutes or less to complete the RAS-DS and rated the instrument as easy or very easy to use. Qualitative data from both consumers and staff indicated that, for most, the RAS-DS was an easy to use, meaningful resource that facilitated shared understandings and collaborative goal setting. However, for a very small number of consumers, the instrument was too confronting and hard to use. Rasch analysis demonstrated evidence for excellent internal reliability and validity. Raw scores were highly correlated with Rasch-generated overall scores and thus no transformation is required, easing use for clinicians. Preliminary evidence for sensitivity to change was demonstrated. CONCLUSIONS: The results provide evidence of the feasibility and psychometric strengths of the RAS-DS. Although further research is required, the RAS-DS shows promise as a potential addition to the national suite of routine outcome measures.