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

AIDS. 2016 Nov 28;30(18):2831-2834. doi: 10.1097/QAD.0000000000001279.

Abstract

Objective: Dolutegravir (DGV) is one of the preferred antiretroviral agents in first-line combination antiretroviral therapy (cART). Though considered to be a well tolerated drug, we aimed to determine the actual rate, timing and detailed motivation of stopping DGV in a real-life clinical setting.

Design: A cohort study including all patients who started DGV in two HIV treatment centers in The Netherlands.

Methods: All cART-naïve and cART-experienced patients who had started DGV were identified from the institutional HIV databases. Clinical data, including motivation and timing of discontinuation of DGV, were extracted from the patient files. Factors that potentially influenced discontinuation of DGV were compared between patients who stopped or continued DGV by multivariate and Kaplan-Meier analyses.

Results: In total, 556 patients were included, of whom 102 (18.4%) were cART-naïve at initiation of DGV. Median follow-up time was 225 days. Overall, in 85 patients (15.3%), DGV was stopped. In 76 patients (13.7%), this was due to intolerability. Insomnia and sleep disturbance (5.6%), gastrointestinal complaints (4.3%) and neuropsychiatric symptoms such as anxiety, psychosis and depression (4.3%) were the predominant reasons for switching DGV. In regimens that included abacavir, DGV was switched more frequently (adjusted relative risk 1.92, 95% confidence interval 1.09-3.38, P log-rank 0.01). No virologic failures were observed.

Conclusion: A relatively high rate of preliminary discontinuation of DGV due to intolerability was detected in our patient population. In particular, DGV was stopped more frequently if the regimen included abacavir. Multiple factors may explain these unexpected postmarketing observations, which warrant further investigation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Retroviral Agents / adverse effects*
  • Anti-Retroviral Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Antiretroviral Therapy, Highly Active / methods*
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy*
  • Heterocyclic Compounds, 3-Ring / adverse effects*
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Male
  • Medication Adherence*
  • Middle Aged
  • Netherlands
  • Oxazines
  • Piperazines
  • Product Surveillance, Postmarketing
  • Pyridones
  • Withholding Treatment
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir