Changes in functional connectivity in people with HIV switching antiretroviral therapy

J Neurovirol. 2020 Oct;26(5):754-763. doi: 10.1007/s13365-020-00853-0. Epub 2020 Jun 4.

Abstract

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects.

Keywords: Attention; HIV; Memory; Neuropsychological assessment; fMRI.

MeSH terms

  • Adult
  • Alkynes / therapeutic use
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • Asymptomatic Diseases
  • Benzoxazines / therapeutic use
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / virology
  • Connectome / methods*
  • Cyclopropanes / therapeutic use
  • Drug Substitution / methods*
  • Emtricitabine / therapeutic use
  • Executive Function / drug effects
  • Executive Function / physiology
  • Female
  • HIV Infections / diagnostic imaging
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • HIV Infections / virology
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology
  • Middle Aged
  • Neuropsychological Tests
  • Oxazines / therapeutic use
  • Piperazines / therapeutic use
  • Prospective Studies
  • Pyridones / therapeutic use
  • Raltegravir Potassium / therapeutic use
  • Rilpivirine / therapeutic use
  • Tenofovir / therapeutic use

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Raltegravir Potassium
  • Tenofovir
  • dolutegravir
  • Rilpivirine
  • Emtricitabine
  • efavirenz

Associated data

  • EudraCT/2014-002284-15
  • EudraCT/2014-003710-84