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Cerebral Small Vessel Disease Signal Similar in Older Men With vs Without HIV
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9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris
Mark Mascolini
White-matter hyperintensities volume (WMHV), a signal of cerebral small-vessel disease (CSVD), did not differ significantly between HIV-positive and negative men 50 or older [1]. The results add to the list of divergent findings on this issue.
Inflammation, a hallmark of HIV infection, has been linked to CSVD. Research also ties HIV infection to a higher stroke risk [2]. A team at University College London and other centers conducted a magnetic resonance imaging (MRI) study to determine whether HIV is also associated with CSVD. They aimed to explore potential associations between HIV status and WMHV in men 50 years old or older in the United Kingdom. WMHV is a neuroimaging correlate of CSVD.
The UK POPPY cohort includes three demographically matched groups: HIV-positive people 50 or older, HIV-positive people younger than 50, and HIV-negative people 50 or older. The MRI analysis focused on a POPPY subgroup of HIV-positive and negative white men 50 or older. Men with HIV had a viral load below 50 copies on antiretroviral therapy. All participants underwent MRI to assess WMHV. The researchers used linear regression models to explore the association between HIV status and WMHV with adjustment for all factors associated with WMHV in bivariate models (at P < 0.2): age, waist circumference, and high-density lipoprotein (HDL) cholesterol level.
The analysis involved 38 men with HIV and 37 without HIV. The groups were similar in atherosclerosis risk factors including age (median 60 and 59 with and without HIV), HDL cholesterol (1.3 mmol/L, or 50 mg/dL, in both groups), Framingham cardiovascular risk score (median 6.5 and 7.4, P = 0.41), current smoking (23.7% versus 18.9%), and drug use in the past 6 months (31.6% and 29.7%). Compared with HIV-negative men, those with HIV had higher frequencies of prior coronary heart disease (13.2% versus 0, P = 0.05) and syphilis (47.4% versus 21.6%, P = 0.02).
Median (and interquartile range, IQR) WMHV was similar in men with HIV (962 uL, IQR 428 to 2628) and men without HIV (825 uL, IQR 347 to 1969) (P = 0.31). Results were also similar for median WMHV as a percent of intracranial volume (ICV) (0.06 with HIV, 0.05 without HIV, P = 0.29).
Linear regression analysis saw no association between HIV and WMHV/ICV (P = 0.78). That analysis did link two factors to a larger WMHV/ICV volume: older age (1.7-fold increase in WMHV/ICV for every 10 years, 95% confidence interval [CI] 1.1 to 2.7, P = 0.04) and greater waist circumference (1.3-fold increase in WMHV/ICV for every 10 cm, 95% CI 1.0 to 1.7, P = 0.06).
The researchers believe their findings "suggest there is no association between HIV status and CSVD." They noted that their results agree with those of two previous studies of WMHV measured by MRI [3,4]. But two other MRI studies--one measuring WMHV, the other using radiologic visual rating scales--did see more CSVD in people with HIV than in HIV-negative controls [5,6]. The researchers suggested these contrasting results could reflect differences in selecting controls and measurement techniques.
References
1. Haddow L, Sudre C, Cardoso MJ, et al. Magnetic resonance imaging of cerebral small vessel disease in HIV positive and HIV negative men aged 50 and above. 9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris. Abstract WEPEB0482.
2. Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system. J Acquir Immune Defic Syndr. 2012;60:351-358.
3. Seider TR, Gongvatana A, Woods AJ, et al. Age exacerbates HIV-associated white matter abnormalities. J Neurovirol. 2016;22:201-212.
4. Watson C, Busovaca E, Foley JM, et al. White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV. J Neurovirol. 2017;23:422-429.
5. Su T, Wit FW, Caan MW, et al. White matter hyperintensities in relation to cognition in HIV-infected men with sustained suppressed viral load on combination antiretroviral therapy. AIDS. 2016;30:2329-2339.
6. Moulignier A, Savatovsky J, Godin O, et al. Cerebral small-vessel disease in HIV-infected patients well controlled on cART. Conference on Retroviruses and Opportunistic Infections. Seattle, 2017. Abstract 75.
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from Jules: perhaps the reason they found no difference between HIV+ vs HIV-neg is because the 2 groups were similar at leaf based on the Table 1 Particpant characteristics below. But generally HIV+ have more metabolic abnormalities, may have a greater background history of alcohol & illicit drug use. HIV itself however can affects blood vessels and there is chronic inflammation & immune activation with HIV+.In HIV-uninfected individuals, white matter hyperintensities (WMH), neuroimaging correlates of cerebrovascular disease, have been associated with cognitive decline, particularly among individuals at increased risk for cardiovascular disease (CVD).Cerebrovascular disease and cerebral blood flow (CBF) are assumed to be interrelated, and the extent of WMH burden is associated with CBF decline over time - from AIDS study referenced below, which interestingly studied patients only 45-60, which is the age population from the CROI study that found a difference between HIV+ vs HIV-neg and they did not find a difference in the over 60 group. This study at IAS did not separate participants out by age group. Perhaps that may be a reason for the finding. In the AIDS study waist circumference was reported & HIV+ had greater WC but vascular stiffness was the same in HIV+ & HIV-neg. Inflammation markers were greater in the HIV+ group in the AIDS study: also 47% were ion protease inhibitors while the POPPY study does not specify which ARTs participants were on; nadir CD4 was low at 170.
here is link to CROI study:
CEREBRAL SMALL-VESSEL DISEASE IN HIV-INFECTED PATIENTS WELL CONTROLLED ON cART - (02/28/17)
References:
[1] Sudre CH, Cardoso MJ, BouvyWH, et al. Bayesian model selection for pathological neuroimaging data applied to white matterlesion segmentation. IEEE Transactions on Medical Imaging2015; 34: 2079-2102.
[2] Seider TR, Gongvatana A, Woods AJ, et al. Age exacerbates HIV-associated white matter abnormalities. J Neurovirol2016; 22: 201-12.
[3] Watson C, Busovaca E, Foley JM, et al. White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV. J Neurovirol2017 [Epub ahead of print].
[4] Morgello S, Murray JM, Van Der Elst S and Byrd DA. HCV, but not HIV, is a risk factor for cerebral small vessel disease. Neurol Neuroimmunol Neuroinflamm2014; 1:1-7.
[5] Su T, Wit FW, Caan MW, et al. White matter hyperintensities in relation to cognition in HIV-infected men with sustained suppressed viral load on combination antiretroviral therapy. AIDS2016; 30: 2329-39.
[6] Moulignier A, Savatovsky J, Godin O, et al. Cerebral small-vessel disease in HIV-infected patients well controlled on cART. Conference on Retroviruses and Opportunistic Infections. Seattle, USA, 2017: Abstract #75.
[7] Pathai S, Weiss HA, Lawn SD, et al. Retinal arterioles narrow with increasing duration of anti-retroviral therapy in HIV infection: a novel estimator of vascular risk in HIV? PLoS ONE2012; 7: e51405.
[8] Haddow LJ, Laverick R, Leung I, et al. Retinal vascular calibres in HIV positive men over 50 years compared to similarly aged HIV negative and younger HIV positive controls. British HIV Association Spring Conference. Liverpool, UK, 2017: Abstract P98.
Contact: lewis.haddow@ucl.ac.uk
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