Influence of efavirenz and 8-hydroxy-efavirenz plasma levels on cognition and central nervous system side effects

© 2023 British HIV Association..

OBJECTIVES: To investigate whether efavirenz (EFV) or 8-hydroxy-EFV (8-OH-EFV) plasma levels are associated with neurocognitive impairment and central nervous system (CNS) side effects.

METHODS: We conducted a cross-sectional analysis to explore the potential links between EFV/8-OH-EFV levels and cognitive performance or CNS-related side effects in patients screened within a randomized trial involving a switch from EFV to rilpivirine. The Mann-Whitney test was employed to compare drug levels in patients with or without cognitive impairment, depression, anxiety, sleep disorder or CNS symptoms. Additionally, Spearman's test was used to assess correlations between drug levels and test scores.

RESULTS: Among 104 patients, neither EFV nor 8-OH-EFV levels were linked to cognitive impairment, although trends towards higher EFV levels were observed in those with impaired executive function (p = 0.055) and language performances (p = 0.021). On the other hand, elevated 8-OH-EFV levels, but not EFV levels, were associated with more CNS side effects (222 vs. 151 ng/mL, p = 0.027), depressive symptoms (247 vs. 164 ng/mL, p = 0.067) and sleep impairment (247 vs. 164 ng/mL, p = 0.078). Consistently, a trend towards a correlation between EFV levels and lower z-scores in executive function and motor function was observed, while 8-OH-EFV levels, but not EFV levels, were directly correlated with symptom scores.

CONCLUSIONS: Higher levels of 8-OH-EFV were associated with CNS side effects, while EFV levels were only marginally associated with cognitive performance, thus suggesting that EFV and its metabolite may act differently in determining detrimental neurological effects.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

HIV medicine - 25(2024), 4 vom: 04. Apr., Seite 491-497

Sprache:

Englisch

Beteiligte Personen:

Ranzani, Alice [VerfasserIn]
Castelli, Francesco [VerfasserIn]
Di Biagio, Antonio [VerfasserIn]
d'Arminio Monforte, Antonella [VerfasserIn]
D'Avolio, Antonio [VerfasserIn]
Soria, Alessandro [VerfasserIn]
Bai, Francesca [VerfasserIn]
Focà, Emanuele [VerfasserIn]
Taramasso, Lucia [VerfasserIn]
Calcagno, Andrea [VerfasserIn]
Bresciani, Elena [VerfasserIn]
Torsello, Antonio [VerfasserIn]
Bonfanti, Paolo [VerfasserIn]
Lapadula, Giuseppe [VerfasserIn]

Links:

Volltext

Themen:

8‐hydroxy‐efavirenz
8-hydroxyefavirenz
Alkynes
Anti-HIV Agents
Benzoxazines
Central nervous system side effects
Cyclopropanes
Efavirenz
JE6H2O27P8
Journal Article
Neurocognitive impairment
P8S49CKH6L
Toxicity

Anmerkungen:

Date Completed 05.04.2024

Date Revised 05.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/hiv.13600

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365956589