Effects of early HIV infection and combination antiretroviral therapy on intrinsic brain activity: a cross-sectional resting-state fMRI study

Figures & data

Table 1 Neurocognitive scales and corresponding cognitive domains

Neurocognitive scales	Cognitive domains
Animal Verbal Fluency Test (AFT)	Verbal fluency
Wisconsin Card Sorting Tests (WCST-64)	Executive function
Trail Marking Test A (TMT-A)	Speed of information processing
Grooved Pegboard (dominant and non-dominant hands)	Complex motor skills
Continuous Performance Test-Identical Pair (CPT-IP) Wechsler Memory Scale (WMS-Ⅲ) Paced Auditory Serial Addition Test (PASAT)	Attention/working memory (three tests)
Hopking Verbal Learning Test (HVLT-R) Brief Visuospatial Memory Test (BVMT-R)	Learning and delayed recall (two tests)

Table 2 Demographic, clinical, and neruopsychological data of the three groups

	HIV+/cART+ (n=26)	HIV+/cART– (n=23)	Healthy controls (n=25)	p-value
Sex (M/F)	24/2	22/1	24/1	0.814^^
Age (years) (mean±SD)	33.1±5.4	31.3±3.7	33.2±6.1	0.344^‡
Education (years), median (IQR)	16 (16–18)	16 (15–18)	16 (16–18)	0.975^‡‡
Disease course (months), median (IQR)	31.5 (12–115)	3 (1–35)	/	0.000^|||
Duration of infection without medication (months), median (IQR)	2.5 (1–42)	3 (1–35)	/	0.822^|||
Duration of cART treatment (months) (mean±SD)	30.8±20.2	/	/	/
CD4^+ (cells/ml) (mean±SD)	524.8±208	465.4±185	/	0.299^||
CD4^+/CD8^+ ratio (mean±SD)	0.75±0.51	0.46±0.11	/	0.009^||
Plasma viral load (mean±SD)	TND	19,850±42,252	/	/
Scores of cognitive performance (mean±SD)
Verbal fluency	45.8±7.0	44.2±9.3	/	0.509^||
Attention/working memory	40.6±6.7	40.6±6.4	/	0.990^||
Executive function	53.5±10.5	53.7±7.9	/	0.951^||
Memory (learning/delayed recall)	43.4±8.6	41.5±7.0	/	0.410^||
Speed of information processing	45.6±9.4	48.3±9.0	/	0.304^||
Fine motor	43.5±9.8	47.3±6.7	/	0.125^||
Cognitive status (ANI/Non-HAND)	12/14	7/16	/	0.26^^

Note: Significant level p<0.05.

Abbreviations: HIV+/cART+, HIV patients experiencing stable cART; HIV+/cART–, treatment-naïve HIV individuals; M, male; F, female; TND, undetectable; ANI, asymptomatic neurocognitive impairment; HAND, HIV-associated neurocognitive disorders; ^, χ² test; ‡, one-way ANOVA; ‡‡, Kruskal–Wallis test; /, no data available; |||, Mann–Whitney U test; ||, independent sample Student t–test.

Table 3 Regions showing ALFF differences among cART+, cART–, and healthy control subject groups

	Brain regions	Montreal Neurologic Institute coordinates (mm)			Number of clusters	Peak t value
	X	Y	Z
HIV+/cART+ vs HC	Right caudate	15	−6	0	57	4.71
	Right superior temporal cortex	60	−36	21	46	4.12
	Right middle cingulum cortex	12	3	39	110	4.76
	Right middle frontal cortex	36	6	51	79	4.70
	Right postcentral cortex	57	−15	45	51	4.11
	Right superior and middle occipital cortex	15	−87	18	397	−5.34
	Left superior and middle occipital cortex	−14	−88	18	402	−5.44
	Left cuneus	−9	−87	24	183	−4.42
	Right calcarine	18	−90	9	139	−4.59
	Right precuneus	9	−57	63	91	−4.91
	Left postcentral cortex	−21	−33	69	126	−3.64
HIV+/cART– vs HC	Right caudate	18	12	12	49	4.20
	Left caudate	−6	18	9	53	5.00
	Right lingual	18	−81	−3	53	−4.35
	Right calcarine	18	−81	−3	42	−5.35
	Right inferior occipital cortex	18	−81	−3	29	−4.65
HIV+/cART+ vs HIV+/cART-	Right superior temporal cortex	60	−39	21	108	3.98
	Right supramarginal cortex	63	−36	24	32	4.49

Note: t value, a positive value represents the ALFF value of the former group, which is higher than the latter, and a negative value represents a decrease.

Abbreviations: ALFF, amplitude of low-frequency fluctuation; HIV+/cART+, HIV patients experiencing stable cART; HC, healthy controls; HIV+/cART–, treatment-naïve HIV individuals.

Figure 1 ALFF maps show the differences among HIV+/cART+, HIV+/cART–, and HC groups. F test revealed significant differences located in bilateral occipital lobes. In comparison with HC, patients in HIV+/cART+ group showed significantly lower ALFF values in bilateral occipital lobes and higher ALFF values mainly in the right frontoparietal lobe and caudate; individuals in HIV+/cART– group showed significantly lower ALFF values in the right occipital lobe and higher ALFF values in bilateral caudate. Compared with HIV+/cART–, HIV+/cART+ showed significantly higher ALFF in right superior temporal gyrus and supramarginal gyrus.

Abbreviations: ALFF, amplitude of low-frequency fluctuation; HIV+/cART+, HIV patients experiencing stable cART; HC, healthy controls; HIV+/cART–, treatment-naïve HIV individuals.

Figure 2 The differences in altered ALFF values in bilateral occipital lobes among HIV+/cART+, HIV+/cART–, and HC groups. Bar graph showed the normalized ALFF values in the occipital cortex. Significantly decreased ALFF values are found in HIV+/cART+ and HIV+/cART– groups compared with HC, respectively. HIV+/cART+ group was lower than that of the HIV+/cART– group, but the difference was not statistically significant.

Note: *, statistically significant.
Abbreviations: NS, nonsignificant; ALFF, amplitude of low-frequency fluctuation; HIV+/cART+, HIV patients experiencing stable cART; HIV+/cART–, treatment-naïve HIV individuals; HC, healthy controls.

Figure 3 Relationship between ALFF values and clinical variables and cognitive performances in HIV patients. Normalized ALFF values of the right occipital cortex positively correlated with CD4⁺/CD8⁺ ratio and executive function in HIV+/cART.

Abbreviations: ALFF, amplitude of low-frequency fluctuation; HIV+/cART+, HIV patients experiencing stable cART.