Altered Brain Function in Young HIV Patients with Syphilis Infection: A Voxel-Wise Degree Centrality Analysis

Figures & data

Table 1 Demographic, Clinical and Neruopsychological Data of the Three Groups

	HIV+/Syphilis+ (n=44)	HIV+/Syphilis- (n=45)	Healthy Controls (n=43)	P value
Sex(M/F)	43/1	42/3	39/4	0.38^※
Age (years) (mean±SD)	32.11±6.96	31.23±6.21	33.09±6.27	0.36＊
Education (years), median (IQR)	16 (15–18)	16 (15–18)	16 (16–18)	0.96^§
HIV infection (months), median (IQR)	22 (12–34)	22 (4–41)	/	0.92^﹟
CD4^+ (cells/mL) (mean±SD)	497.45±206.59	507.07±217.05	/	0.81^∆
CD4^+/CD8^+ ratio(mean±SD)	0.60±0.41	0.61±0.38	/	0.83^∆
cART/untreated	36/8	37/8	/	0.95^※
Ratio of TND of HIV viral load	34/44	35/45	/	0.95^※
Verbal fluency(mean±SD)	44.32±8.76	46.82±8.05	/	0.16^∆
Attention/working memory(mean±SD)	41.66±8.08	45.17±9.88	/	0.07^∆
Executive function(mean±SD)	53.67±9.11	56.51±10.60	/	0.18^∆
Memory (learning/delayed recall) (mean±SD)	42.74±8.56	45.78±7.63	/	0.08^∆
Speed of information processing(mean±SD)	44.34±9.44	47.54±9.07	/	0.11^∆
Complex motor skills (mean±SD)	42.59±10.08	47.60±8.71	/	<0.05^∆
Cognitive status (ANI/Non-HAND)	18/26	16/29	/	0.60^※

Notes: ^※, χ² test; ＊, One-way analysis of variance; ^§, Kruskal–Wallis test; ^﹟, Mann–Whitney U-test; /, No data available; ^∆, Independent two-sample t-test. Significant level P<0.05.

Abbreviations: HIV+/syphilis+, HIV patients with syphilis coinfection; HIV+/syphilis-, HIV patients without syphilis coinfection; M, male; F, female; IQR, interquartile range; SD, standard deviation; ANI, asymptomatic neurocognitive impairment; HAND, HIV-associated neurocognitive disorders; TND, target not detected.

Table 2 Brain Regions with DC Differences Among the Three Groups

	Brain Regions	BA	MNI Coordinates (mm)	Number of Clusters	Peak t value
			(x, y, z)
[HIV+/syphilis+]>HC	Left IFC (Oper/Tri)	44/45	−45, 12, 3	387	4.99
	Bilateral PCC/PCu	7/23	−3, −54, 15	283	5.08
	Left IPL	40	−51, −24, 36	264	4.68
	Right OFC	10	24, 48, 6	275	−4.35
[HIV+/syphilis-]>HC	Left IPL	40	−57, −30, 12	252	4.75
	Right OFC	10	39, 30, −18	260	−5.12
[HIV+/syphilis+]>[HIV+/syphilis-]	Left LOC	19	−51, −75, 9	267	−4.39

Abbreviations: HCs, healthy controls; BA, Brodmann’s area; MNI, montreal neurological institute; IFC (Oper/Tri), inferior Frontal cortex (Oper/Tri); PCC/PCu, posterior cingulated cortex/precuneus; IPL, inferior parietal lobe; OFC, orbital-frontal cortex; LOC, lateral occipital cortex (P<0.005, cluster number = 249, corrected).

Figure 1 DC differences among HIV+/syphilis+, HIV+/syphilis- and HC groups.

Notes: F-test of ANOVA showed DC differences mainly located in bilateral frontal cortex, left occipital cortex, and bilateral inferior parietal lobule (yellow). HIV+/syphilis+ showed decreased DC in the right frontal cortex and increased DC in the bilateral inferior parietal cortex and left occipital cortex. HIV+/syphilis- showed decreased DC in the right frontal cortex and increased DC in the left inferior parietal cortex. Compared with HIV+/syphilis-, HIV+/syphilis+ displayed decreased DC in the left occipital cortex. (P<0.005, cluster number = 249, α = 0.05, corrected). Increased DC was shown in red, while decreased DC was shown in green.

Abbreviations: ANOVA, analysis of variance; DC, functional connectivity density; HIV+/syphilis+, HIV patients with syphilis coinfection; HIV+/syphilis-, HIV patients without syphilis coinfection; HC, healthy controls.

Figure 2 Pearson correlation between DC values and clinical variables and cognitive metrics in HIV+/cART+.

Notes: The mean z value of DC in the right orbital-frontal cortex was positively correlated to the CD4+ cell counts (r = 0.366, P = 0.014) (A). The mean z value of DC in the left inferior parietal lobe was negatively correlated to the executive function score (r = −0.314, P = 0.038) (B).