Background:
The brain’s central executive network (CEN) plays a key role in the pathogenesis of depression, problematic substance use, and cognitive impairment, all of which are common comorbidities of HIV. Previous cross-sectional research has reported that resting-state functional connectivity (rsFC) in the CEN is lower in people living with HIV (PLWH) compared to participants without HIV, suggesting reduced integrity of the CEN in PLWH. But it is unclear when these alterations emerge and what clinical markers predict their emergence.
Methods:
Resting state functional magnetic resonance imaging scans were conducted at baseline and two-year follow-up in a cohort (median age=29) of PLWH in early HIV infection (n=49) and healthy controls (n=20). A sub-sample (n=50, six female, 44 male) completed scans at both timepoints. Blood samples were collected to measure clinical immune markers and plasma HIV RNA. Regression models adjusting for age and sex were used to predict longitudinal change scores for CEN rsFC.
Results:
In the overall sample, CEN rsFC increased from baseline to follow-up (mean change=+13.4% ; 95% confidence interval [CI]: +2.2%, +25.1%). We detected no differences by HIV status in CEN rsFC at baseline or follow-up and no differences by HIV status in CEN rsFC change scores. Among PLWH, those infected longer at baseline (i.e., with detectable HIV antibodies and no longer in acute HIV) exhibited more negative CEN rsFC change scores (β=-0.78; 95% CI:-1.50, -0.06). Higher absolute CD4 counts at baseline predicted more positive CEN rsFC change scores (β=0.5; 95% CI:0.17, 0.83). Due to the small number of female participants, it was not possible to calculate sex-stratified effect estimates.
Conclusions:
In the overall sample, CEN rsFC increased over time. Among PLWH, these gains in CEN rsFC were substantially weaker among those with evidence of greater immunopathology at baseline, as indexed by lower CD4 count. Gains in CEN rsFC were weaker among those infected longer at baseline, as indicated by the presence of detectable HIV antibodies. These findings suggest that HIV-related differences in CEN rsFC not yet apparent in early infection, but greater immunopathology in early infection alters early longitudinal trajectories of CEN rsFC. CD4 nadir may be an important prognostic marker for reduced CEN rsFC later in life in PLWH. Interventions that preserve CEN rsFC (e.g., non-invasive neuromodulation) may protect against emergence of psychiatric and neurocognitive comorbidities in PLWH.