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 VE-822 raltegravir use. Elvitegravir and dolutegravir were respectively investigated in 5 studies each. The 1494675-86-3 distributor average study population size was 202, the average study duration 48 weeks. All but four of the included studies were 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 updates and evidence levels per category can be found in Table 2, the studies and data used in the meta-analysis are listed in Table 3. Subsequently a meta-analysis of virological outcome was performed on the 16 controlled studies that compared an INI-based regimen with placebo or other drug classes for similar indications and in which similar endpoints could be evaluated. This resulted in three subcategories and the exclusion of studies on treatment intensification, due to the absence of comparable endpoints. The results of the meta-analysis are visualized in Forest plots. Low heterogeneity in the outcome was seen in the treatment-naive subgroup and the patients switching successful suppressive therapy group. Higher heterogeneity was seen in the studies for patients experiencing virological failure, which points to a higher inter-study variation on virological outcome. When assessing the immunological response after start of INIs, the majority of the controlled studies with raltegravir, elvitegravir or dolutegravir indicate a similar median CD4 increase compared to other regimens. However, in therapy-naive patients and the long-term follow-up of all reported significantly higher CD4 increments compared to efavirenz-based therapies. In the subgroup of treatment-experienced patients with virological failure, use of raltegravir resulted in significant better immunological outcome in BENCHMRK 1 and 2 compared to placebo. ODIS reported similar significant results after switching to raltegravir from a boosted PI. The INIs are generally well tolerated and rarely Grade 3 or 4 treatment-emerging adverse events are reported. Compared to efavirenz, discontinuation from INIs due to clinical adverse events is infrequent, while compared to PIs, less severe and lifethreatening laboratory abnormalities are observed.
