Virawudh Soontornnitomkij, M.D.

• M.D. , Faculty of Medicine Ramathibodi Hospital , Mahidol University, Thailand (1986)
• Residency in Anatomic Pathology , Pathology, Ramathibodi Hospital , Mahidol University, Thailand(1992)
• Residency in Anatomic Pathology , Pathology, Vanderbilt University Medical Center , Vanderbilt University, USA(1995)
• Fellowship in Neuropathology , Pathology, University of Iowa Hospitals and Clinics , University of Iowa, USA(1996)
• Fellowship in Neuropathology , Pathology, University of Pittsburgh Medical Center ,University of Pittsburgh, USA(1998)
• Postdoctoral Research ,Pathology and Laboratory Medicine (Neuropathology),University of California Los Angeles, USA (2008)
• Postdoctoral Research, Psychiatry (NeuroAIDS) University of California San Diego, USA(2012)

Regional distribution of HIV-1 RNA load in the brain

My neuroAIDS research prior to the era of combination antiretroviral therapy focused on the importance of brain HIV viral load and HIV encephalitis in mediating HIV-associated dementia. A variety of techniques to quantify HIV in the brain had led to vastly different results in different laboratories. Our group pioneered the reproducible quantification of HIV-1 RNA in brain tissue homogenates to determine the regional distribution of brain viral loads in AIDS autopsies. We applied two highly sensitive RNA assays based on either signal amplification (branched-DNA assay, Quantiplex HIV RNA, Chiron Corporation) or template amplification (RT-PCR assay, Amplicor HIV-1 Monitor, Roche Molecular Systems). We found a good correlation between these two techniques in quantitative performance. In addition, the HIV-1 RNA load generally correlated well with HIV gp41 protein load assessed by our immunohistochemical semi-quantitative scoring system. Of the truly quantitative techniques, HIV-1 RNA assays of tissue homogenates held the greatest promise for objective cross-study comparisons. We also demonstrated that productive HIV infection was not uniformly distributed throughout the brain, but was preferentially localized to certain anatomical regions.

• Soontornniyomkij V, Nieto-Rodríguez JA, Martínez AJ, Kingsley LA, Achim CL, Wiley CA. Brain HIV burden and length of survival after AIDS diagnosis. Clinical Neuropathology 1998;17:95–99. PMID: 9561331.
• Wiley CA, Soontornniyomkij V, Radhakrishnan L, Masliah E, Mellors J, Hermann SA, Dailey P, Achim CL. Distribution of brain HIV load in AIDS. Brain Pathology 1998;8:277–284. PMID: 9546286.
• Soontornniyomkij V, Wiley CA. Quantification of HIV in the central nervous system. NeuroAIDS, Volume 1, Issue 1, 1998 
• Wiley CA, Achim CL, Christopherson C, Kidane Y, Kwok S, Masliah E, Mellors J, Radhakrishnan L, Wang G, Soontornniyomkij V. HIV mediates a productive infection of the brain. AIDS 1999;13:2055–2059. PMID: 10546857.

Cerebral β-amyloid angiopathy in Alzheimer's disease

A significant proportion of dementing illnesses in the elderly are attributed to multiple pathologic processes that may confer their additive or synergistic effects to the development of cognitive decline. Cerebral β-amyloid angiopathy is common in elderly individuals, especially those affected with Alzheimer's disease. Our autopsy study showed direct association between severe cerebral β-amyloid angiopathy and microinfarct burden in Alzheimer's disease brains. Frequent microinfarcts in demented individuals with severe cerebral β-amyloid angiopathy might contribute a vascular component to the cognitive impairment in these patients.

I also accomplished in optimizing a protocol of immunogold silver staining for β-amyloid on semi-thin resin-embedded brain tissue sections and demonstrated a spatial association of β-amyloid deposits in capillary walls and perivascular neuropil, supporting a hypothesis of deficiencies in perivascular drainage in mediating cerebral β-amyloidosis.

• Anders KH, Wang ZZ, Kornfeld M, Gray F, Soontornniyomkij V, Reed LA, Hart MN, Menchine M, Secor DL, Vinters HV. Giant cell arteritis in association with cerebral amyloid angiopathy: immunohistochemical and molecular studies. Human Pathology 1997;28:1237–1246. PMID: 9385928.
• Soontornniyomkij V, Lynch MD, Mermash S, Pomakian J, Badkoobehi H, Clare R, Vinters HV. Cerebral microinfarcts associated with severe cerebral β-amyloid angiopathy. Brain Pathology 2010:20:459–467. 
• Soontornniyomkij V, Choi C, Pomakian J, Vinters HV. High-definition characterization of cerebral β-amyloid angiopathy in Alzheimer’s disease. Human Pathology 2010;41:1601–1608. 

Immunohistologic correlates of age-related memory impairment in animal models

The differential susceptibility to the development of age-related memory impairment may be driven by genetic polymorphisms, epigenetic phenomena, and dissimilar life-long environmental exposure to stressors. Neurobiological substrates contributing to memory impairment in old age largely remain unclear. I applied immunohistochemistry and computer-assisted image analysis to study protein expression levels in mouse brains in correlation with novel object recognition memory performance. I developed a protocol for measuring immunoreactivity levels within anatomic areas of interest using the Image-Pro Analyzer software.

• Soontornniyomkij V, Risbrough VB, Young JW, Wallace CK, Soontornniyomkij B, Jeste DV, Achim CL. Short-term recognition memory impairment is associated with decreased expression of FK506 binding protein 51 in the aged mouse brain. Age 2010;32:309–322. 
• Soontornniyomkij V, Risbrough VB, Young JW, Soontornniyomkij B, Jeste DV, Achim CL. Increased hippocampal accumulation of autophagosomes predicts short-term recognition memory impairment in aged mice. Age 2012;34:305–316. 
• Soontornniyomkij V, Risbrough VB, Young JW, Soontornniyomkij B, Jeste DV, Achim CL. Hippocampal calbindin-1 immunoreactivity correlate of recognition memory performance in aged mice. Neuroscience Letters 2012;516:161–165. 

Interaction effect of APOE ε4 genotype and cerebral β-amyloid plaque deposition on HAND

The apolipoprotein E (APOE) ε4 allele enhances cerebral accumulation of β-amyloid and is a major risk factor for sporadic Alzheimer’s disease. It is possible that the APOE ε4 genotype and cerebral β-amyloid deposition play a role in the development of HIV-associated neurocognitive disorders (HAND). We conducted a clinicopathological study using brain tissue specimens from the National NeuroAIDS Tissue Consortium (NNTC) and showed that β-amyloid plaques in HIV brains were immunohistologically different from those in symptomatic Alzheimer's disease brains. Nonetheless, cerebral β-amyloid plaque deposition was associated with HAND in APOE ε4 carriers but not in non-ε4 carriers. The detection of APOE ε4 genotype and cerebral β-amyloid deposition biomarkers might be useful in identifying living HAND subjects who could benefit from β-amyloid-targeted therapies.

• Soontornniyomkij V, Achim CL. Cerebral β-amyloid deposition and HIV-associated neurocognitive impairment. Alzheimer Research Forum, January 2010 
• Soontornniyomkij V, Moore DJ, Gouaux B, Soontornniyomkij B, Tatro ET, Umlauf A, Masliah E, Levine AJ, Singer EJ, Vinters HV, Gelman BB, Morgello S, Cherner M, Grant I, Achim CL. Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. AIDS 2012;26:2327–2335. 
• Soontornniyomkij V, Achim CL. Aging. In: Gendelman HE (ed) The Neurology of AIDS, 3rd ed. Oxford University Press, Oxford, 2012, pp. 567–580.

Antiretroviral medications and brain aging changes

HAND remains prevalent in patients who receive antiretroviral therapy and may be associated with cumulative exposure to antiretroviral medications and other factors. We proposed that chronic toxic effects of antiretroviral drugs could contribute to brain aging changes, which might be one of the key underpinnings of HAND. We conducted a clinicopathological study using brain tissue specimens from the NNTC and showed that protease inhibitor-based antiretroviral therapy might increase the risk of cerebral small vessel disease and thereby neurocognitive impairment in HIV-infected adults. In a subsequent study, we found that darunavir use was associated with neuronal phospho-tau pathology in the putamen.

• Soontornniyomkij V, Umlauf A, Chung SA, Cochran ML, Soontornniyomkij B, Gouaux B, Toperoff W, Moore DJ, Masliah E, Ellis RJ, Grant I, Achim CL. HIV protease inhibitor exposure predicts cerebral small vessel disease. AIDS 2014;28:1297–1306. 
• Soontornniyomkij V, Umlauf A, Soontornniyomkij B, Gouaux B, Ellis RJ, Levine AJ, Moore DJ, Letendre SL. Association of antiretroviral therapy with brain aging changes among HIV-infected adults. AIDS 2018;32:2005–2015.

• Characterization of Aging Brain Pathology in Thailand Chakri Naruebodindra Medical Institute (CNMI) 2021/01/01 – 2022/12/31 Role: Principal Investigator
• Effects of Antiretroviral Therapy on Brain Small Vessel Aging U.S. NIH: R56 AG059437 2017/09/30 – 2019/08/31 Role: Principal Investigator
• Bardoxolone: A Novel Treatment for HIV-associated Neurocognitive Disorders U.S. NIH: R21 MH115825 (PI: Levine, Andrew) 2018/09/01 – 2020/06/29 Role: Consortium Principal Investigator at University of California San Diego
• Disentangling Alzheimer’s Disease and HIV-associated Neurocognitive Disorder: Identifying Unique Neuropsychological Profiles with Distinct Biomarker and Neuropathological Signatures      U.S. NIH: RF1 AG061070 (PI: Moore, David/Bondi, Mark) 2018/09/30 – 2020/06/29 Role: Co-Investigator
• California NeuroAIDS Tissue Network (CNTN) U.S. NIH: U24 MH100928 (PI: Moore, David/Achim, Cristian) 2018/03/01 – 2020/06/29 Role: Co-Investigator
• Translational Methamphetamine AIDS Research Center (TMARC) U.S. NIH: P50 DA026306 (PI: Grant, Igor) 2014/06/01 – 2019/05/31