Serotonergic and Dopaminergic Function in Neuropsychiatrically Asymptomatic People With HIV on Antiretroviral Therapy

People with HIV (PWH) on antiretroviral therapy (ART) still experience neurocognitive dysfunction and accelerated brain volume loss. To assess whether the serotonergic and dopaminergic systems are affected, we used [¹¹C]DASB positron emission tomography (PET) to assess presynaptic serotonergic function and [¹⁸F]FDOPA PET to measure presynaptic dopaminergic reserve in neurocognitively and psychiatrically asymptomatic PWH on ART, compared to seronegative controls (SCs).

We compared [¹¹C]DASB binding (BP_ND) (n = 17 PWH/19 SCs) and [¹⁸F]FDOPA influx constant (K_i) (n = 20 PWH/19 SCs) of PWH and SCs. We assessed correlations of K_i and BP_ND with CSF cytokines and imaging/clinical/neuropsychological outcomes using multivariable and univariable models.

BP_ND, K_i, and neurocognitive and psychiatric scores did not differ between PWH and SCs. Higher BP_ND correlated with better neurocognitive scores in the whole group. K_i did not correlate with neurocognitive scores. Neither BP_ND nor K_i correlated with depression scores. Caudate and putamen MRI volumes trended smaller in PWH. While CSF inflammatory cytokines were higher in PWH, they did not correlate with either PET measure.

Presynaptic serotonin transporter density (measured by [¹¹C]DASB) is a good correlate of the neurocognitive function in PWH and SCs. Despite long-term ART, PWH still showed trends for basal ganglia volume loss, consistent with known disproportionate global and regional volume loss in PWH compared to SCs. Aspects of serotonergic and dopaminergic function, namely, presynaptic SERT density and dopaminergic reserve, however, are not different in this PWH cohort on ART from SCs, despite persistent neuroinflammation and trends of volume loss. This could reflect a functional compensatory process versus minimal, below-detection-level dysfunction.