Comparative efficacy, safety and durability of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: an update on a systematic review and network meta-analysis.

Background: The objective of this study was to assess the durability of response of dolutegravir (DTG) as an antiretroviral core agent by comparing its efficacy and safety with other recommended or commonly used core agents up to 96-weeks (W96).

Methods: A previously published systematic review was updated to identify phase 3/4 randomised controlled trials (RCTs) of core agents in treatment-naïve HIV-1 patients. Efficacy [virologic suppression (VS), CD4 cell change from baseline] and safety [adverse events [AEs], discontinuations, drug-related AEs [DRAEs]] were analysed at W96 using Bayesian network meta-analysis (NMA) adjusting for nucleoside/nucleotide reverse transcriptase inhibitors' (NRTIs') backbone.

A practical approach to predict expansion of evidence networks: a case study in treatment-naive advanced melanoma.

Network meta-analysis (NMA) is a statistical method used to produce comparable estimates of efficacy across a range of treatments that may not be compared directly within any single trial. NMA feasibility is determined by the comparability of the data and presence of a connected network. In rapidly evolving treatment landscapes, evidence networks can change substantially in a short period of time.

Value and usability of unpublished data sources for systematic reviews and network meta-analyses.

Peer-reviewed publications and conference proceedings are the mainstay of data sources for systematic reviews and network meta-analyses (NMA), but access to informative unpublished data is now becoming commonplace. To explore the usefulness of three types of 'grey' literature-clinical trials registries, clinical study reports and data from regulatory authorities-we conducted four case studies. The reporting of outcome data in peer-reviewed publications, the clinical trials registries and the clinical study reports for two clinical trials-one in melanoma, one in juvenile idiopathic arthritis (JIA)-was examined.

An adult zebrafish model for preclinical tuberculosis vaccine development.

Tuberculosis remains a major global health challenge despite extensive vaccination schemes with the current live vaccine, Bacillus Calmette-Guérin. Tuberculosis vaccine research has been hampered by a scarcity of animal models which replicate human disease and are suitable for large-scale studies. We have shown recently that Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, causes an infection resembling human tuberculosis in adult zebrafish (Danio rerio).

Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.

The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (≈ 35 bacteria) of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%), stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs.