Adverse Events of Raltegravir and Dolutegravir

Luigia Elzi; Stefan Erb; Hansjakob Furrer; Matthias Cavassini; Alexandra Calmy; Pietro Vernazza; Huldrych Günthard; Enos Bernasconi; Manuel Battegay

Disclosures

AIDS. 2017;31(13):1853-1858. 

In This Article

Results

During the study period from 1 April 2006 to 31 December 2015, 4041 HIV-infected individuals participating in the SHCS started an antiretroviral regimen containing either raltegravir (n = 2091) or dolutegravir (n = 1950). Baseline characteristics are shown in Table 1. Dolutegravir was mostly combined with abacavir–lamivudine in a single-tablet regimen in comparison with raltegravir being most often combined with tenofovir–emtricitabine.

Of 4041 patients included in this study, 568 (14.1%) patients had modification of their ART because of any reason during the first year of treatment, corresponding to 15.5 [95% confidence interval (CI) 14.5–16.9] discontinuations per 100 patient-years. Among them, 364 (17.4%) patients were treated with raltegravir and 204 (10.5%) with dolutegravir (Table 1).

The main reason for treatment modification was convenience (n = 302) expressed by the patient's wish, physician's decision or treatment simplification, followed by toxicity or intolerance (n = 181). Only 10 patients under raltegravir (0.48%) and two patients under dolutegravir (0.10%) demonstrated virological failure (Table 1).

In multivariable analysis, risk factors of ART modification within the first year of treatment regardless of the main reason were female sex (hazard ratio 1.28, 95% CI 1.06–1.53, P = 0.009), younger age (hazard ratio 0.90, 95% CI 0.83–0.98 per 10 years older, P = 0.011), HIV RNA more than 100 000 copies per ml at baseline (hazard ratio 1.49, 95% CI 1.09–2.02, P = 0.011), and starting a raltegravir-containing regime (hazard ratio 1.71, 95% CI 1.38–2.08, P < 0.001; S1 Table. Supplementary material, http://links.lww.com/QAD/B135). Among pregnant women, those treated with dolutegravir were more likely to discontinue ART compared with those treated with raltegravir. However, this difference was not statistically significant (P = 0.205).

Adverse events leading to ART modification within the first year occurred in 4.5% of the patients, corresponding to a discontinuation rate of 4.4 (95% CI 3.6–5.5) per 100 patient-years for dolutegravir and 5.7 (95% 4.7–6.9) per 100 patient-years for raltegravir. This difference did not reach statistical significance (P = 0.11). In multivariate analysis, the only independent risk factor for ART modification because of toxicity was female sex (hazard ratio 1.98, 95% CI 1.45–2.71, P < 0.001; Table 2).

Neuropsychiatric complaints, although observed in less than 2% of the patients, were the most commonly reported toxicity adverse events and more frequently in the dolutegravir group [discontinuation rate of 1.83 (95% CI 1.30–2.57) per 100 patient-years] compared with the raltegravir group [discontinuation rate of 0.70 (95% CI 0.41–1.21) per 100 patient-years, P = 0.002]. In multivariable analysis of the subgroup with neurotoxicity, there was a lower risk of discontinuation for raltegravir compared with dolutegravir (hazard ratio 0.46, 95% CI 0.22–0.96, P = 0.037; S2 Table. supplementary material, http://links.lww.com/QAD/B135).

Gastrointestinal adverse events were the second most common reason for ART modification and reported in 19 dolutegravir-treated patients and only in six patients under raltegravir. Allergies and lipid disorders as reason for ART modification were more frequent in raltegravir (16 and 12, respectively) than dolutegravir (four and one, respectively) patients. There were only seven immune reconstitution syndrome events after initiation of a INSTI-containing regimen, six in the raltegravir group and one in the dolutegravir group (P = 0.076) (Table 1).

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