Background:
Development and progression of cerebral white matter hyperintensities (WMH) are associated with increased risk of stroke and cognitive impairment for people with (PWH) and without HIV (PWOH). Individuals with chronic HIV have greater WMH burden compared to PWOH despite viral suppression. Progression of WMH in relation to outcomes following onset of early antiretroviral therapy (ART) remains poorly understood.
Methods:
We identified participants enrolled in the SEARCH010/RV254 cohort in Thailand. Multimodal 3T MRI and cognitive testing was performed at week 0 (Fiebig I-V, at ART onset) and week 96 post-ART initiation for all participants. WMH data were extracted from T2 FLAIR sequences using an automated k-nearest neighbor approach. Total WMH volume was computed as both a raw index and as a standardized percentage of the intracranial volume (ICV) for each individual. A composite cognitive score (NPZ-4) was created by averaging Z-scores for Color Trails 1 & 2, Grooved Pegboard Non-dominant, and Trail Making A. HIV disease indices, vascular comorbidities, and cognitive scores were compared to WMH indices using nonparametric testing.
Results:
We identified 71 participants (70 male) with AHI and median age 27 years (IQR 24-33). Median CD4+ T-cell count was 348 (IQR 251, 481) and 674 (IQR 486, 908) at week 0 and 96. Median VL at week 0 was 6.16 logcopies/mL (IQR 5.43, 6.78). 96% of participants were virally suppressed (VL <50 copies/mL) at week 96. We observed a mean increase in standardized WMH volume of 22% from week 0 to 96, with 53 individuals (75%) showing an absolute increase and 18 individuals (25%) showing an absolute decrease. While presence of vascular comorbidities was low (9% hypertension, 1% diabetes, 7% hyperlipidemia, and 3% migraine), we found positive associations between WMH % change and history of smoking and systolic blood pressure at week 0, as well as between raw WMH change and BMI, pulse pressure, systolic blood pressure, and hypertension at week 0 (all p<0.05). We did not find an association between WMH burden and cognitive test scores.
Conclusions:
Individuals with AHI showed an increase in WMH volume over two years following initiation of ART. Modifiable vascular risk factors during AHI correlated with WMH progression despite successful ART. These findings implicate vulnerability of white matter following acute infection despite early and effective initiation of ART. Further studies comparing these patterns to PWOH and individuals with chronic HIV are needed.
