Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in...

Area of Science:

• Neuroscience
• Pharmacology
• Infectious Diseases

Background:

• Antiretroviral therapy (ART) is crucial for managing HIV.
• Cognitive impairment can affect people with HIV (PWH).
• Understanding drug concentration effects on cognition is important for treatment optimization.

Purpose of the Study:

• To examine the relationship between plasma concentrations of specific antiretroviral drugs and cognitive function in PWH.
• To investigate lamivudine (3TC), abacavir (ABC), emtricitabine (FTC), and tenofovir (TFV) pharmacokinetics (PK) in relation to cognitive performance.

Main Methods:

• The POPPY study cohort provided pharmacokinetic and cognitive data from PWH on 3TC/ABC or FTC/TDF regimens.
• Cognitive function was assessed using Cogstate across six domains.
• Rank regression analysis was used to correlate PK parameters (AUC0-24, Cmax, Ctrough) with cognitive z-scores, adjusting for confounders.

Main Results:

• Higher 3TC area under the concentration-time curve over 24 hours (AUC0-24) and trough concentrations (Ctrough) correlated with better global cognitive z-scores.
• Higher 3TC maximum concentration (Cmax) was associated with poorer cognitive z-scores, independent of abacavir levels.
• No significant associations were found between abacavir, emtricitabine, or tenofovir PK parameters and cognitive function.

Conclusions:

• While abacavir, emtricitabine, and tenofovir plasma exposure did not show a clear impact on cognitive function, lamivudine exposure demonstrated a complex relationship.
• Higher overall lamivudine exposure was generally linked to better cognitive performance, whereas higher peak lamivudine concentrations were associated with poorer performance.