Cerebral Function in Perinatally HIV Infected Young People and HIV Uninfected Sibling Controls

A study by Ashby and colleagues aimed to characterise the neurocognitive function of young adults with perinatally acquired HIV (paHIV) infection and compare them to their HIV negative siblings or family members as aged matched controls.

The study had two arms, group 1 was made up of 33 perinally infected HIV-positive young people aged 16-25, group 2 was a control group of 14 HIV-negative young people matched by age who were aware of their family member’s HIV status. Both groups completed a series of computerised neurocognitive tests, prospective and retrospective memory questionnaires (PRMQ) and the International HIV Dementia Scale (IHDS) testing. There was an additional sub-study, which involved Magnetic Resonance Spectroscopy (MRS) scanning of which all candidates were eligible. The MRS sub-study used 8 participants from group 1 and 4 from group 2.

The two groups were evenly matched in terms of demographics as shown in Table 1.

Of the 33 young people in group 1 who were HIV-positive, the median CD4 count was 444 cells/mm³ (IQR: 174-725), median CD4% was 21%, 18 (55%) young people had a HIV viral load of <50 copies/mL. The median age at diagnosis was 5 years (IQR: 0-9) with the median number of years since diagnosis of 15 (IQR: 13-20). Currently 26 (79%) of young people were on ARVs with the median age of starting ARVs being 13 years (IQR: 8-13) and the number of years since starting ARVs being 8.5 years (IQR: 4-13).

The results are shown in Tables 2 and 3. Results are mean scores unless otherwise stated. The only significantly different result from neurocognitive panel of tests between the two groups was the Prospective and Retrospective Memory Questionnaire (PRMQ) test where group 2 scored lower than group 1.

However, the MRS sub-study results showed significant differences between the two groups in terms of concentrations of Chol/Cr and MI/Cr. This indicates significant increases in cerebral metabolite inflammatory factors despite the fact that 5/8 people in group 1 had a plasma viral load of <50 cells/mm³.

Table 1: Baseline Demographics
Parameter	Group 1	Group 2
Number of subjects	33	14
Number of subjects undergoing MRS	8	4
Age, years (mean, range)	20, 17-23	20, 16-24
Black/Mixed ethnicity (%)	85	86
Male gender, n (%)	11(33)	4 (29)
Recent recreational drug use (%)	2 (6)	1 (7)
Ever used recreational drugs (%)	13 (39)	6 (43)
English is first language (%)	29 (88)	13 (93)
Number of years education (years)	14	15

Table 2: Results of Neurocognitive Tests in HIV-Positive Children and Age-Matched HIV-Negative Siblings
Domain	Best score	Total score (n=47)	Group 1 (n=34)	Group 2 (n=14)	p (for group differences)
Speed	Low	10.64	10.66	10.57	0.27
Executive function	Low	17.83	18.18	17.00	0.68
Accuracy	High	3.02	3.03	2.99	0.78
IHDS	High	-	11.3	11.3	0.861
PRMQ (IQR)	Low	-	42 (36-49)	35 (28-43)	0.023

Table 3: Results of the Sub-Group MRS Study
		Best score	Total score	Group 1 (n=8)	Group 2 (n=4)	p
Right Basal Ganglia	NAA/Cr	High	20.21	2.13	1.77	0.17
	Chol/Cr	Low	0.76	0.83	0.63	0.02
	MI/Cr	Low	3.30	3.43	3.03	0.09
Key: Cr = creatine, Chol = choline, MI = myo-inositol, NAA – N-Acetyl Aspartate

Comment

This is the first study to looked at neurological function in HIV-positive children using MRS with an appropriate HIV-negative control group.

While the clinical implications are unclear this is clearly an aspect of paediatric care that demands further research, especially given the expanding interest in questions related to HIV and ageing, and the potential role of HIV-mediated inflammation in people with unsuppresed viraemia.

Reference

1. Ashby J et al. Cerebral function in perinatally HIV infected young people and HIV uninfected sibling controls. 17th Annual BHIVA Conference, 6–8 April 2011, Bournemouth. Oral abstract O30.