Purpose of review: Results from nonrandomized cohort studies suggest higher risks of CNS adverse events for dolutegravir, versus other ARVs. There have been two case reports of myocarditis on dolutegravir. Integrase inhibitors have been associated with IRIS in two cohort studies. Meta-analysis of randomized trials can be used to cross-check potential safety signals. This systematic review of drug safety used an EMBASE and MEDLINE search combined with serious adverse event (SAE) reports on the website www.clinicaltrials.gov. Cardiovascular, CNS or IRIS-associated adverse events were analysed for dolutegravir versus other ARVs. Relative risks for the comparison between dolutegravir and other antiretrovirals were calculated for each adverse event. Meta-analyses applied Mantel-Haenszel random-effects models.
Recent findings: There was a higher risk of Grade 1-4 insomnia adverse events for DTG (6.1%) versus other ARVs (4.5%; P = 0.02). There was no significant difference between DTG and other ARVs in the risk of cardiovascular serious adverse events. In the SINGLE and SPRING-1 trials comparing DTG with efavirenz, there were 5/465 patients with reported suicidality SAEs on DTG (1.1%) versus 6/469 (1.3%) on EFV. In other studies, serious adverse events of suicidality were reported for 15/2250 patients on DTG (0.7%) versus 9/2257 patients on other ARVs (0.4%). Risks of IRIS were low, but event rates were low and the main trials excluded CDC stage C disease.
Summary: In this meta-analysis, there was no significant effect of dolutegravir on the risk of cardiac, IRIS or suicide-related serious adverse events. There was a higher risk of insomnia for DTG. Other completed randomized trials should be included in new evaluations of DTG safety. Continued pharmacovigilance, with regular meta-analyses, should be used to monitor safety.