Impact of Early ART Initiation on Neurocognitive Function in HIV – A Randomized Trial
Appelmans, Eline A.
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University of Washington Abstract Impact of Early ART Initiation on Neurocognitive Function in HIV – A Randomized Trial Eline A Appelmans Chair of the Supervisory Committee: Ann Duerr Affiliate Professor Global Health Epidemiology Objective During the early stages of HIV infection, the virus invades the central nervous system (CNS), causing inflammation and neuronal damage. Untreated, this damage may cause cognitive impairment known as HIV-associated neurocognitive disorder (HAND). The optimal timing of antiretroviral therapy (ART) initiation required to prevent HAND remains unknown. We hypothesized that immediate ART initiation prevents neurocognitive impairment. Design Prospective longitudinal randomized study. Method Between 2012 and 2017 in Lima, Peru, HIV infection was identified by monthly HIV Ab/RNA testing in the Sabes study of HIV-negative men who have sex with men and transgender women. Participants with CD4 counts greater than 350 were randomized to receive ART (FTC/TDF/EFV or FTC/TDF/COBI/EVG) immediately or at 24 weeks after diagnosis. Participants underwent full neuropsychological (NP) testing of 8 functional domains at baseline and 12, 24, and 48 weeks from enrollment. Total neurocognitive performance was measured via total z scores using site-specific normative data. We compared total z score and change in total z score (from baseline) at week 48 between immediate and deferred ART groups. Result 88 subjects were enrolled into this neuropsychological study and had their baseline NP assessment at a median of 47 days from estimated infection date. There was an increase in total z score over time in both arms, consistent with neurocognitive improvement. At week 48, the NP domain of processing speed had a change from baseline that was lower among subjects randomized to deferred treatment than among those treated immediately. Overall the change in total z score from baseline was the same amongst randomization arms. Conclusion These preliminary results suggest that HIV care that includes ART initiation very shortly after HIV acquisition led to improvement in participants' speed of processing performance over time. This unique randomized cohort offers a rigorous assessment of the consequences that delays in ART initiation may have on neurocognitive function. Long term follow-up will provide valuable insights on the further evolution of neurocognitive functioning. Keywords Neurocognitive, Acute Infection, Antiretroviral Treatment, Central Nervous System (CNS)
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