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Neurotoxicities in the treatment of HIV between dolutegravir, rilpivirine and dolutegravir/rilpivirine: a meta-analysis
  1. Anthony Allen Reeves1,
  2. Andrea V Fuentes1,
  3. Joshua Caballero1,
  4. Jennifer E Thomas1,
  5. Juan F Mosley II1,
  6. Catherine Harrington2
  1. 1Department of Clinical and Administrative Sciences, Larkin University College of Pharmacy, Miami, Florida, USA
  2. 2Lloyd L Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, Florida, USA
  1. Correspondence to Dr Anthony Allen Reeves, Department of Clinical and Administrative Sciences, Larkin University College of Pharmacy, Miami, FL 33169, USA; a.allenreeves13{at}


Objective To assess the risk of neuropsychiatric adverse effects (ie, depression, anxiety, insomnia, dizziness, suicidal behaviour) among patients treated with rilpivirine, dolutegravir and dolutegravir/rilpivirine.

Design This is a systematic review and meta-analysis of randomised controlled trials. Quality of evidence was assessed using Jadad scoring system.

Data sources Three electronic databases were searched for available publications up to 1 May 2020. Searches included relevant studies, trial registers, conference proceeding abstracts and grey literature.

Inclusion criteria Randomised controlled trials with data focused on adult participants (ie, 18 years of age or older) receiving dolutegravir 50 mg, rilpivirine 25 mg or combination of dolutegravir 50 mg/rilpivirine 25 mg once daily.

Results Twenty studies with a minimum duration of 48 weeks and average Jadad score of 4 were included (n=10 998). Primary objective demonstrated a relative risk (RR) synergistic effect on depressive symptoms for dolutegravir/rilpivirine (RR=2.82; 95% CI (1.12 to 7.10)) when compared with dolutegravir (RR=1.10; 95% CI (0.88 to 1.38)) and rilpivirine (RR=1.08; 95% CI (0.80 to 1.48)). Secondary objectives showed no difference between dolutegravir, rilpivirine and dolutegravir/rilpivirine to efavirenz. Additionally, excluding efavirenz studies, dolutegravir and dolutegravir/rilpivirine yielded increased depression (RR=1.34; 95% CI (1.04 to 1.74)).

Conclusion The combination of dolutegravir/rilpivirine appears to increase the risk of depressive symptoms. Despite the increase, the clinical significance is unknown and needs further study. Additionally, neurotoxicity risk appears similar between dolutegravir, rilpivirine and dolutegravir/rilpivirine antiretroviral therapy when compared with efavirenz-based antiretroviral therapy.

  • anti-retroviral agents
  • HIV
  • patient care management

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  • Handling editor Laith J Abu-Raddad

  • Contributors AAR developed the research question and methods section, and developed the search strategy. AAR and AVF selected eligible studies during the title/abstract screening and full-text evaluation. AAR and AVF extracted data from the included studies and appraised the quality of the evidence. JC, JET and JFM reviewed data extraction and appraisal of evidence. AAR and CH coordinated RevMan V.5.3 implementation. AAR entered extracted data into RevMan V.5.3 and interpreted/analysed the data. AVF, JC, JET and JFM double-checked data entry into RevMan V.5.3 and reviewed data interpretation. CH was involved in cases of dissent with respect to extracted data/evaluations, and participated in analysing and interpreting the data. AAR developed the draft of the manuscript. AVF, JC, JET, JFM and CH contributed to the final editing of the draft. AAR and JC coordinated contributions of the coauthors and compiled the final draft.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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