Uptake and discontinuation of integrase inhibitors (INSTIs) in a large cohort setting. JAIDS
Greenberg et al. on behalf of the RESPOND Study Group aimed to describe the characteristics of patients initiating integrase strand transfer inhibitors (INSTIs) for the first time in heterogeneous real-world settings across Europe and Australia. In this analysis, RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG), or raltegravir (RAL) after January 1, 2012 were included.
Overall, 9’702 persons were included; 5’051 (52.1%) starting DTG, 1’933 (19.9%) EVG, and 2’718 (28.0%) RAL. The likelihood of starting RAL or EVG vs DTG decreased over time and was higher in Eastern and Southern Europe compared with Western Europe. At 6 months after initiation, 8.9% (95% confidence interval: 8.3% to 9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, and 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, and 19.8% RAL). Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and previous non–AIDS-defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months.
In conclusion, uptake of DTG compared with EVG/c or RAL has increased over calendar time, and more in Western Europe compared with other European regions. INSTI discontinuation was mainly due to toxicity in the first 6 months and patient/physician choice thereafter, but was low overall. Discontinuation was significantly higher for RAL, mainly due to treatment simplification, whereas discontinuation due to nervous system toxicities was highest on DTG. Our findings highlight the need for further research to better understand adverse events on INSTIs