Intolerance of dolutegravir-containing combination antiretroviral therapy regimens in real-life clinical practice

Boer, M.G.J. de; Berk, Guido E.L. van den; Holten, N. van; Oryszcyn, Josephine E.; Dorama, W.; Moha, Daoud Ait; Brinkman, Kees

doi:10.1097/qad.0000000000001279

Cited by 165 publications

(161 citation statements)

References 11 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…TDs were mainly attributable to toxicity of study drugs, with neuropsychiatric events being the most frequent adverse events. This is in agreement with previous reports on DTG and with the recent SWORD trial , further highlighting the potential neuropsychiatric toxicity of DTG. As a consequence of its viral potency and high genetic barrier, DTG represents a good option in two‐drug maintenance regimens.…”

Section: Discussionsupporting

confidence: 93%

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV‐1 replication

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV‐1 replication

et al. 2018

View full text Add to dashboard Cite

show abstract

“…We identified higher rates of discontinuation because of any toxicity—but not because of NPAEs—in women, in agreement with some cohort studies and an open‐label RCT with dolutegravir recruiting only women . In the latter, rates of NPAEs including insomnia, depression or depressed mood, and suicidal ideation were similar between dolutegravir and atazanavir, and participant‐reported treatment satisfaction was significantly higher with dolutegravir .…”

Section: Discussionsupporting

confidence: 88%

“…Discontinuation of dolutegravir because of NPAEs was not more frequent after February 2016, when increased awareness of treating physicians of the possibility of dolutegravir being the drug responsible for NPAEs could be expected after some initial reports in international conferences . Therefore, we cannot confirm or refute the possibility that physician awareness had a significant biasing effect on this association.…”

Section: Discussionmentioning

confidence: 87%

Discontinuation of dolutegravir, elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort

et al. 2019

View full text Add to dashboard Cite

Objectives The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. Methods A population‐based, prospective, multicentre cohort study was carried out. Treatment‐naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV‐1 RNA < 50 HIV‐1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double‐checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. Results A total of 4165 subjects (37% treatment‐naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1–2, and had been present before and improved after drug withdrawal. Conclusions In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.

show abstract

“…In contrast, a report by de Boer et al . emphasized an unexpectedly high risk of discontinuation of dolutegravir because of CNS toxicity (13.7%), particularly when combined with abacavir. Furthermore, a more recent study by Peñafiel et al .…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of switching to dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (TDF) or elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed HIV‐infected patients in clinical practice: results from a multicentre, observational study

et al. 2018

View full text Add to dashboard Cite

Objectives The aim of the study was to compare the efficacy and tolerability of switching antiretroviral therapy to dolutegravir + emtricitabine/tenofovir disoproxil fumarate (TDF) with those of switching to elvitegravir/cobicistat/emtricitabine/TDF in clinical practice. Methods In a multicentre real‐life observational study, we analysed data for HIV‐infected patients on antiretroviral treatment with viral load < 50 HIV‐1 RNA copies/mL switching to dolutegravir + emtricitabine/TDF (dolutegravir group) or elvitegravir/cobicistat/emtricitabine/TDF (elvitegravir group). Follow‐up was censored at 48 weeks. Results The 48‐week estimated proportion maintaining virological efficacy was 96.1% with dolutegravir (n = 123) and 95.4% with elvitegravir (n = 186; P = 0.941). Patients in the dolutegravir group showed more treatment discontinuations, but these were mainly as a result of simplification. The elvitegravir group showed more discontinuations because of renal adverse events (2.7% versus 0% with dolutegravir). Interestingly, no difference was observed between the two regimens in central nervous system toxicity‐related discontinuations. Switching to dolutegravir was associated with a better blood lipid profile. Conclusions Switching to dolutegravir + emtricitabine/TDF was associated with similar efficacy and tolerability to switching to elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed patients in clinical practice, although reasons for discontinuation showed differences between regimens. These results should be interpreted with caution, as this is a nonrandomized comparison.

show abstract

Intolerance of dolutegravir-containing combination antiretroviral therapy regimens in real-life clinical practice

Cited by 165 publications

References 11 publications

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV‐1 replication

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV‐1 replication

Discontinuation of dolutegravir, elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort

Efficacy and safety of switching to dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (TDF) or elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed HIV‐infected patients in clinical practice: results from a multicentre, observational study

Contact Info

Product

Resources

About