Neurotoxicities in the treatment of HIV between dolutegravir, rilpivirine and dolutegravir/rilpivirine: a meta-analysis

Sex Transm Infect. 2021 Jun;97(4):261-267. doi: 10.1136/sextrans-2020-054821. Epub 2021 Mar 29.

Abstract

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.

Keywords: HIV; anti-retroviral agents; patient care management.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Alkynes / adverse effects*
  • Alkynes / therapeutic use
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Benzoxazines / adverse effects*
  • Benzoxazines / therapeutic use
  • Cyclopropanes / adverse effects*
  • Cyclopropanes / therapeutic use
  • Depression / chemically induced
  • Drug Combinations
  • HIV Infections / drug therapy
  • Heterocyclic Compounds, 3-Ring / adverse effects*
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Neurotoxicity Syndromes / etiology*
  • Oxazines / adverse effects*
  • Oxazines / therapeutic use
  • Piperazines / adverse effects*
  • Piperazines / therapeutic use
  • Pyridones / adverse effects*
  • Pyridones / therapeutic use
  • Randomized Controlled Trials as Topic
  • Rilpivirine / adverse effects*
  • Rilpivirine / therapeutic use

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Drug Combinations
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir, rilpivirine drug combination
  • dolutegravir
  • Rilpivirine
  • efavirenz