excluded reports if they dealt with non-clinical factors or described only pharmacokinetic and pharmacodynamic data. Case reports and studies with small patient cohorts were excluded and subsequently full-length articles were retrieved from all published papers. The flow diagram is depicted in Figure 1. All selected articles or abstract-only reports were carefully read and analyzed. The quality assessment of the studies selected in the Fumarate hydratase-IN-1 systematic review is depicted in Figure 2. We assessed the strength of evidence by using the GRADE approach. In this way, a body of evidence is evaluated regarding four major domains: risk of bias, consistency, directness and precision of study outcomes. This results in four strength of evidence grades: high, moderate, low or insufficient. In order to reveal differences between virological efficacy and ancillary benefits, we extracted modified intention-to-treat as well as ontreatment and as-treated data. mITT includes all patients who received at least one dose of study drug and completed the study, missing data are considered as failures, as are non-completers. OT includes only the patients completing the study at the analyzed endpoint. Patient-data were censored in case of toxicity, loss to follow-up, lack of efficacy before the endpoint is reached and other reasons. AT is similar to OT, but includes patients with virological failure before the endpoint is reached. Only controlled studies with virological outcome data comparing INI versus another compound or placebo were included. If data were not available in the paper, authors were contacted and invited to provide it. The systematic review resulted in 48 eligible studies on the clinical use of integrase inhibitors, of which 15 abstract-only reports. These studies include in total more than 9400 HIV-infected patients. Of these studies, 38 described interventions regarding raltegravir use. Elvitegravir and dolutegravir were respectively investigated in 5 studies each. The average study population size was 202, the average study duration 48 weeks. All but four of the included studies were 1000998-59-3 prospective, the majority randomized and multi-centered. Blinding was performed in 48 of the studies, 20 studies were single-armed. Study characteristics of all studies with latest result up