Integrase inhibitors are now preferred antiretrovirals in first line cART. Dolutegravir (DGV) is possibly considered as one of the most efficacious, convenient and tolerated INSTI, with hardly any chance for drug-drug interactions. Since we encountered many patients who stopped DGV because of intolerance, we analyzed the experience with DGV in our whole patient population since licensing in the Netherlands.
In our hospital cohort we retrospectively analyzed all patients who started DGV, either as initial therapy or after switching from other antiretrovirals for any reason. Baseline characteristics at the moment of DGV start were recorded. We calculated the proportion of patients who stopped DGV, analyzed the reason for interruption and evaluated potential risk factors. We used the Chi-squared test to check for significant differences between groups.
In our cohort of almost 3000 hiv infected patients (97,6% on cART), 388 patients started DGV from August 2014 for a median period of 219 days (range 5-376) and at a median age of 48 years (range 23-77); 46 were female. In total 65 started as naieves (median CD4 495/mm3 (range 70-1610). One patient died from progressive prostate carcinoma and was excluded form the analysis.
DGV treatment was stopped in 62/387 (16,0%) patients after a median of 78 days (range 5-327). Of the naieves 9/65 (13,8%) stopped DGV compared to 53/322 (16,4%) of non-naieves (p=ns). Of the women 5/46 (10,9%) stopped, compared to 57/341 men (16,7%) (p=ns). Of those who used DGV-only tablets 24/158 (15,6%) stopped, compared to 38/230 (16,5%) using combination-tablet (with ABC/3TC) (p=ns). Main reason for DGV interruption was intolerance in 55/62 (88,7%) patients: 19/55 (34,5%) sleeping problems, 18/55 (32,7%) gastrointestinal problems, 12/55 (21,8%) psychiatric problems, 7/55(12,7%) headache, 6/55 (10,9%) musculoskeletal problems and 6/55 (10,9%). Some patients reported more than one toxicity. There were no virological failures.
In a real life setting a substantial proportion of patients (16%) unexpectedly interrupted DGV treatment for reasons of intolerance, in particular sleeping-, gastrointestinal- and psychiatric problems. This was much higher than reported in clinical trials, where discontinuation of DGV due to adverse reactions is reported to be less than 3%.