Greater Accumulation of Brain White Matter Hyperintensities in People Diagnosed and Treated During Acute HIV Compared With People Without HIV

Abstract

Background and objectives: People living with HIV (PWH) have increased rates of ischemic stroke even after antiretroviral therapy (ART) and viral suppression. Cerebral white matter hyperintensities (WMHs) on brain MRI are associated with an increased risk of stroke and cognitive impairment. This study sought to characterize and quantify brain WMHs during acute HIV infection and after early ART initiation compared with people without HIV.

Methods: Participants diagnosed with acute HIV infection (AHI) from the RV254/SEARCH010 cohort in Thailand and demographically matched people without HIV (PWoH) were identified. The inclusion criterion was age 18 years or older; exclusion criteria were history of psychiatric disorder, neurologic disorder, or pregnancy. Participants who had paired 3T MRI brain scans completed at enrollment and at two-year follow-up were included in the analysis. WMH data were extracted from T2 fluid-attenuated inversion recovery sequences and standardized to total intracranial volume to generate an index of WMH volume change. A repeated-measures ANOVA was used to test for WMH change over time per group, and WMH change was compared with HIV disease measures and vascular comorbidities using parametric and nonparametric testing.

Results: Seventy-two RV254 participants (PWH, 99% male) and 37 PWoH (100% male), with a mean age of 31 years, were included. PWH had a mean estimated duration of exposure to HIV of 21 days (SD = 9). Both groups had very low rates of vascular comorbidities. At baseline, the volume of WMHs did not differ between groups. However, there was a greater increase in WMH volume over 2 years in PWH (mean 21.6%) compared with PWoH (mean 5.8%, p = 0.004, partial η² = 0.075, Cohen d = 0.597) despite undetectable plasma viral load. Within PWH, hypertension and higher BMI were associated with a greater increase in WMHs (p = 0.038 and p = 0.016, respectively). Greater WMH accumulation also correlated with higher baseline CD4⁺ T-cell count in PWH (r = 0.272, p = 0.021).

Discussion: Young Thai men with AHI demonstrated greater WMH progression than PWoH over 2 years despite ART initiation and viral suppression. These data suggest that brain white matter is vulnerable to HIV during early infection, independent from vascular comorbidities or lifestyle factors. Limitations include homogeneity in sex and ethnicity and follow-up period limited to 24 months.