Abstract Body

The rates of discontinuation (D/C) due to adverse events (AEs) of the integrase strand transfer inhibitors (INSTI) dolutegravir (DTG), raltegravir (RAL) and cobicistat-boosted elvitegravir (EVG/c) have been very low in randomized clinical trials. However, some real-life retrospective series have reported unexpectedly high rates of D/C due to AEs, particularly with DTG. We aimed to compare the D/C rates due to AEs of the three INSTI inhibitors in a prospective multicenter cohort.

The PISCIS Cohort is an ongoing observational study that includes about 21000 HIV-infected patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain). All subjects having started one of these 5 regimens including DTG with abacavir/lamivudine (ABC/3TC) or tenofovir fumarate/emtricitabine (TDF/FTC; regimens A and B, respectively), RAL with ABC/3TC (C) or TDF/FTC (D), or the co-formulation EVG/c/TDF/FTC (E) since July 2013 as their initial regimen or a switch with plasma HIV-1 RNA <50 c/mL were included. The incidence rate and 95% confidence interval [IR (95% CI)] of D/C due to toxicity is estimated as the ratio of the number of discontinuations by 100 patients/year of follow-up. Adjusted hazard ratios (aHR) and their 95% CI were obtained from multivariate Cox models, adjusted for gender, age, transmission group, origin, treatment-naïve and hepatitis B/C co-infection.

Out of 13066 patients on follow-up at July 2016, 2096 subjects were included (90% naives), receiving regimens A (n=859), B (n=108), C (n=208), D (n=280) and E (n=641). Of them, 430 (stopped prematurely their regimen, due to AEs in 74. The corresponding IR (95%CI) for DTG, RAL and EVG/c were 5.1 (3.6-7.0), 3.0 (1.8-4.5), and 2.8 (1.7-4.1), respectively. Among those receiving DTG, the IR with ABC/3TC or TDF/FTC were 4.9 (3.3-6.9) and 6.3 (2.0-12.9), respectively, with no significant differences between them. The aHR of D/C due to AEs with DTG vs. RAL was 1.1 (0.6-2.1), DTG vs. EVG/c 1.6 (0.8-2.9), and EVG/c vs. RAL 0.8 (0.4-1.6).

In subjects starting an initial therapy or a switch regimen with an undetectable plasma HIV-1-RNA, there are no significant differences in the D/C rates due to AEs among those receiving DTG, RAL or EVG/c. For those receiving DTG, there are no significant differences between those receiving ABC/3TC or TDF/FTC. Marginal structural models adjusted for baseline and time-varying confounding variables will be run in further analysis.