Demographic and clinical data of the participants are presented in Table 1. Welch’s Two Sample t-test indicates that there is no statistically significant age difference between the HIV- and HIV + participants (p = 0.324). However, we included age as a covariate in all multivariate regression analyses to control for their remaining confounding effects. Compared to HIV+, HIV- participants had a higher number of males than females (p < 0.001) and higher education levels (p = 0.039) at baseline.
Baseline FW comparison for HIV + vs. HIV- cohorts
Figure 1A-B represents the comparisons of FW between the HIV + and HIV- at baseline for GM and WM. Mean voxel-by-voxel FW map from HIV + cohort is shown in Fig. 1C. Marginal comparisons based on Welch’s two-sample t-test showed that FW index was higher in GM (t = 4.74, adjusted p-value padj <0.001) and in WM (t = 2.11, padj =0.038) in the HIV + cohort than in HIV- cohort (Fig. 1, Table 1).
We also compared the FW in both cohorts categorized by age such as young adults (age ≤30, 22 HIV+, 18 HIV- participants) and older adults (age > 30, 15 HIV+, 32 HIV- participants). FW was significantly higher in GM (t = 10.51, padj<0.001) and WM (t = 4.072, padj<0.001) in the HIV + young adult than HIV- young adult. In contrast, FW was significantly higher only in GM (t = 2.589, padj=0.007) in the HIV + older adult compared to HIV- older adults.
Among 25 ROIs that included subcortical GM structures and WM tracts, 3 ROIs (Thalamus, Amygdala and Hippocampus) had significantly higher FW in the HIV + cohort than in HIV- cohort (p < 0.05) (not shown).
Baseline comparisons of blood marker for HIV + vs. HIV- cohorts
Welch’s two group t-test showed that average NfL concentration was marginally higher in HIV + compared to the HIV- cohort (t = 2.10, p = 0.042) (Table 1).
Short Term effects of cART on FW
In paired comparisons between baseline and week-12 for HIV + participants (n = 31 with measures at both baseline and week-12), we found that the FW index decreased significantly in GM (t = 4.57, padj<0.001) and WM (t = 2.60, padj=0.014) (Fig. 2A-B).
Based on the STM that modeled the cohort and treatment effect simultaneously and adjusted for the confounding effects of age, we found that GM and WM are associated with significant higher FW in the HIV + cohort (βcohort,GM=0.044, padj,GM <0.001; (βcohort,WM=0.005, padj,WM =0.004). Even after accounting for the effects of HIV and treatment, age was significantly associated with the increase of FW for most of the ROIs. More information on individual ROIs can be found in Supplementary Table S1.
Short Term effects of cART on blood markers
Paired t-test showed that the average NfL concentration decreased (t = 1.61, p = 0.115) after 12 weeks of cART treatment (Fig. 2C).
Long Term effects of cART on FW
Paired t-tests revealed that FW increased in WM and GM at year-1 compared to week-12 and baseline for the HIV + and HIV- cohorts respectively (p < 0.05). However, at year-1 and year-2 visits there were no significant differences in GM and WM between the HIV + and HIV- (Fig. 3A-B).
The LTM showed there were no significant cohort effect and the interaction of cohort and visit in GM and WM suggesting that levels of FW in the HIV + cohort were stabilized after 12 weeks of cART treatment (Fig. 3A-B). The LTM on ROIs also revealed similar results as presented in Supplementary Table S2. Age is invariably associated with significant increase of FW.
Long Term effects of cART HIV + on NfL
The average NfL concentrations were found to become stable after 12 weeks (new baseline) of cART treatment and follow-up visits in the HIV + cohort. Similar to FW, after 12 weeks of cART treatment, no significant differences in NfL were found between the HIV + and HIV- cohorts during the follow-up visits (Fig. 3C).
Baseline FW association with blood markers and cognitive performance
Pearson correlation analysis for HIV + at baseline showed that average NfL concentration was correlated with FW in GM and WM (β ≈0.6, padj<0.001). In addition, we found significant positive correlations for FW vs. NfL in 19 of 25 ROIs. The CD4 cell counts were negatively associated with FW in GM and WM (β ≈-0.4, padj=0.041), as well as in 14 out of 25 ROIs. However, no significant correlations were found for FW vs. VL for any ROIs. Details are provided in Supplementary Table S3.
The total cognitive score was also lower in the HIV + cohort compared to the HIV- cohort at baseline (p = 0.028). Paired t-test showed that total cognitive score increased after 12 weeks of cART treatment in HIV + cohort (p < 0.001). After 12 weeks of cART treatment and follow-up visits in HIV + cohort, total cognitive scores became stable. The total cognitive score was not significantly correlated with FW for WM and GM in both cohorts at baseline; however, there was a trend toward a negative correlation in the GM (r= -0.26, p = 0.11). In the STM and LTM, FW in WM and GM were not significantly associated with the total cognitive scores. Visit and interaction between cohort and visit were found significant for FW in WM and GM in the LTM while visit was significant in the STM (padj<0.05).