Dominic Chow | University of Hawaii at Manoa (original) (raw)

Papers by Dominic Chow

AIDS Research and Human Retroviruses, 2019

Increased negative immune checkpoint receptors (NCR) on T cells are linked to T cell exhaustion, ... more Increased negative immune checkpoint receptors (NCR) on T cells are linked to T cell exhaustion, dysfunctional effector responses, and HIV viral persistence. Metformin, an oral hypoglycemic agent used for diabetes, may have previously unrecognized beneficial immunologic effects. Using cryopreserved blood from a 24-week pilot study involving 12 virally suppressed HIV-infected individuals randomized 1:1 to metformin versus observation (OBS), we assessed change in the frequencies of T cell activation (CD38 + HLA-DR +) and NCR [programmed cell death protein 1 (PD1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and T cell mucin-domain containing-3 (TIM3)]. No differences in 24-week change were seen between arms in CD4 or CD8 T cells, in the CD4/CD8 ratio, or in activated (CD38 + HLA-DR +) CD4 or CD8 T cells. However, metformin over 24 weeks led to decreases compared with OBS in single PD1 + (percent decrease:-9.6% vs. 7.5%, p = .015), in dual PD1 + TIGIT + (-15.0% vs. 10.4%, p = .002), and in triple PD1 + TIGIT + TIM3 + (-24.0% vs. 8.1%, p = .041) CD4 T cells. Metformin led to no changes in CD8 T cell NCR frequencies. Metformin decreases the frequency of PD1 + , PD1 + TIGIT + , and PD1 + TIGIT + TIM3 + expressing CD4 T cells. This may have relevance to HIV cure strategies and to efforts to mitigate the risk of chronic complications of HIV.

A descriptive epidemiologic study of HIV-infected individuals in Hawaii: report of the Hawaii Sero-Positivity and Medical Management database (HSPAMM)

Hawaii medical journal, 2002

This is a retrospective study of the HSPAMM database evaluating differences in clinical, laborato... more This is a retrospective study of the HSPAMM database evaluating differences in clinical, laboratory, HIV-risk factors and demographic characteristics with respect to gender and ethnicity. There were no significant differences comparing gender, and Hawaiians and non-Hawaiians with respect to developing a CD4 count < 200 cells/mm3. HSPAMM contains information on a large number of HIV-infected Asians/Pacific Islanders.

Poorer neuropsychological performance increases risk for social services among HIV-infected individuals

Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health, 2013

HIV-Associated Neurocognitive Disorder (HAND) is a prevalent condition among persons with HIV res... more HIV-Associated Neurocognitive Disorder (HAND) is a prevalent condition among persons with HIV resulting in cognitive impairments that may impact daily functioning. The relationship between neuropsychological (NP) test performance and functional status was investigated based on social services received (SSR) among 285 HIV-infected and 242 HIV-negative participants enrolled in the Hawai'i Aging with HIV Cohort. HIV-infected participants scored significantly lower than the HIV-negative group on all measures of NP testing and also reported receiving SSR at a higher rate. Among HIV-infected participants, more SSR correlated with poorer overall global NP performance (ρ = -0.25, P < .001), as well as poorer performance in NP domains assessing psychomotor speed (ρ = -0.25, P < .001), and learning and memory (ρ = -0.19, P = .02). NP test performance did not correlate with the number of SSR among HIV-negative participants. Supplemental Security Income (SSI) was the most commonly uti...

Biologics : targets & therapy, 2008

HIV-associated lipodystrophy syndrome is strongly associated with antiretroviral treatment in pat... more HIV-associated lipodystrophy syndrome is strongly associated with antiretroviral treatment in patients with human immunodeficiency virus (HIV). Niacin is thought to affect hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) expression in peripheral and intra-abdominal fat (IAF). This study investigated the effect of extended-release niacin (ERN) on adipose HSL and LPL expression in patients with HIV-associated lipodystrophy syndrome. Changes in IAF and peripheral fat content and HSL and LPL expression were examined in 4 HIV-infected patients recruited from a prospective study treated with ERN. Patients underwent limited 8 slice computerized tomography abdominal scans, dual-energy X-ray absorptiometry scans, and skin punch biopsies of the mid-thigh at baseline and after 12 weeks of ERN. All subjects were on stable highly active antiretroviral therapy prior to and during the study. Changes in body habitus were self-reported. Normalized HSL expression decreased in 3 patients an...

Disparities in hospitalizations among HIV positive individuals for Native Hawaiians and Asians compared to Whites in Hawai'i

Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health, 2014

Hospitalizations of those living with HIV are expensive and often indicate failures in access to,... more Hospitalizations of those living with HIV are expensive and often indicate failures in access to, or retention in, primary care. Higher rates of hospitalizations among individuals with HIV have been reported in some US ethnic minorities, yet little information is available for Native Hawaiians and Asian subgroups. All hospitalizations in Hawai'i of individuals aged ≥13 years from December 2006-December 2010 were considered. Hospitalizations of individuals with HIV were identified using ICD-9 diagnosis codes of 042 and V08; 613 hospitalizations with an HIV diagnostic code were found. Using Hawaii State Department of Health 2010 data, estimated rates of hospitalizations among HIV positive individuals by race/ethnicity among the 2,600 Hawai'i residents living with HIV were calculated along with estimated rate ratios (using Whites as the reference group). Multivariable adjusted estimated rate ratios (aRR) were calculated with negative binomial models, adjusting for age, sex, and...

Expert Review of Gastroenterology & Hepatology, 2010

Case Reports in Neurological Medicine, 2013

Parkinsonism in SLE is rare. Diffuse leukoencephalopathy is equally uncommon and is associated wi... more Parkinsonism in SLE is rare. Diffuse leukoencephalopathy is equally uncommon and is associated with a poor prognosis. We present a single case of a 50-year-old Filipino man who presented with a generalized discoid rash after starting lisinopril. The rash persisted despite discontinuation of lisinopril, and over the next three months, he developed rapidly progressive parkinsonism. Brain MRI showed symmetric confluent T2-hyperintensities involving the white matter and basal ganglia. Four of the 11 American College of Rheumatology criteria for the classification of SLE were met. A rheumatologist made a diagnosis of SLE with cutaneous and central nervous system involvement. Significant neurologic and radiologic improvement occurred following treatment with IV steroids followed by a prolonged taper. This report highlights a case of subacute parkinsonism with a diffuse leukoencephalopathy as an early manifestation of SLE which resulted in a good recovery following treatment with only immunosuppressive therapy.

Heart Asia, Jan 23, 2010

OBJECTIVES: To determine the autonomic cardiovascular control among residents of Hawaii who are e... more OBJECTIVES: To determine the autonomic cardiovascular control among residents of Hawaii who are exposed to varying levels of volcanic air pollution (vog), which consists largely of sulfur dioxide (SO(2)) and acid aerosols. METHODS: In a cross-sectional study between April 2006 and June 2008, the authors measured cardiovagal autonomic function by heart-rate variability (HRV) in 72 healthy individuals who lived in four exposure zones on Hawaii Island: vog-free (n=18); episodic exposure to SO(2) >200 ppb and acid aerosol (n=19); chronic exposure to SO(2) ≥30 ppb and acid aerosol (n=15); and chronic exposure to acid aerosols (n=20). Individuals with diabetes or heart disease, or who had smoked in the preceding month were excluded. HRV was measured in all subjects during rest, paced breathing and active standing (Ewing manoeuvre). HRV was analysed in time and frequency domains and compared between the four exposure zones. RESULTS: There were no significant differences between exposure...

PLoS ONE, 2014

Background: Rates of insulin resistance are increased in HIV-infected patients on stable antiretr... more Background: Rates of insulin resistance are increased in HIV-infected patients on stable antiretroviral therapy (ART). Such increase may partially be due to HIV-induced immune dysregulation involving monocytes (MO) and its subsets.

Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort

Atherosclerosis, 2015

Association of lipoprotein particle size/number and HDL function with mitochondrial oxidative str... more Association of lipoprotein particle size/number and HDL function with mitochondrial oxidative stress and function may underlie the excess cardiovascular (CVD) risk in HIV. Among HIV infected individuals on stable highly active antiretroviral therapy, we related standard and novel lipid measures [plasma total cholesterol, triglycerides, HDL-C, LDL-C, lipoprotein particle (-P) subclass size and number and HDL function (via cholesterol-efflux capacity)] with oxidative stress [peripheral blood mononuclear cell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s mitochondrial-specific 8-oxo-deoxyguanine (8-oxo-dG)] and function markers [oxidative phosphorylation (OXPHOS) NADH dehydrogenase (Complex I) and cytochrome c oxidase (Complex IV) enzyme activities]. Multivariable-adjusted logistic and linear regression analyses were employed adjusting for age, gender, CD4 nadir, viral load, smoking, diabetes, HOMA-IR, hypertension and lipid medications. Among 150 HIV-infected persons (mean age 52 years, 12% women, median CD4 count 524 cell/mm3), low HDL-C and high total cholesterol/HDL-C ratio were related to PBMC 8-oxo-deoxyguanine (p = 0.01 and 0.02 respectively). Large HDL-P and HDL-P size were inversely related to PBMC 8-oxo-deoxyguanine (p = 0.04). Small LDL-P (p = 0.01) and total LDL-P (p = 0.01) were related to decreased OXPHOS Complex I activity. LDL-P was related to decreased OXPHOS Complex IV activity (p = 0.02). Cholesterol efflux capacity was associated with increased OXPHOS Complex IV activity. HDL concentration and particle size and number are related to decreased PBMC mitochondrial oxidative stress whereas HDL function is positively related to mitochondrial oxidative function. The association we find between atherogenic lipoprotein profile and increased oxidative stress and function suggests these pathways may be important in the pathogenesis of cardiometabolic disease in HIV disease.

Mitochondrion, 2004

We describe a 50-year-old Caucasian man with a family history of myoclonic epilepsy associated wi... more We describe a 50-year-old Caucasian man with a family history of myoclonic epilepsy associated with ragged red fibers (MERRF) and a diagnosis of Human Immunodeficiency Virus (HIV). The patient had multiple risk factors for contracting HIV and was being followed in our clinic at the time of his diagnosis. Initial testing following seroconversion revealed a baseline CD4C T-lymphocyte count of 652!10 6 cells/l and a HIV-1 RNA of 14,781 copies/ml. He reported exercise intolerance and had mild neurologic deficits, which worsened around the time of HIV seroconversion. These symptoms led to his subsequent diagnosis of MERRF by the detection of the A8344G point mutation in the tRNA Lys gene of mitochondrial DNA (mtDNA). The baseline estimated proportion of mutant genome was 39%. He showed a rapid course of HIV disease progression with a CD4C T-lymphocyte nadir of 174!10 6 cells/l associated with a HIV-1 RNA of 238,178 copies/ml, within 17 months following HIV seroconversion. To avoid further mitochondrial insult, which could result from the use of a standard nucleoside reverse transcriptase inhibitor-containing regimen, a protease inhibitor regimen consisting of hard-gel saquinavir (Invirasee), and lopinavir/ritonavir (Kaletrae) was chosen for this patient. The patient's CD4C T-lymphocyte count increased to 282! 10 6 cells/l and his viral load became undetectable 7 months following the initiation of antiretroviral therapy. His neurologic symptoms did not worsen on this antiretroviral regimen. When initiating HIV therapy in individuals with metabolic myopathies related to mitochondrial dysfunction, it may be important to design an antiviral regimen that minimizes mitochondrial damage, yet effectively maintains durable viral suppression. q

Anaerobic Metabolic Responses to Maximal Exercise Testing in HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy

Medicine & Science in Sports & Exercise, 2008

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2011

Aerobic Fitness Levels and Validation of a Non Exercise VO_2max Prediction Equation for HIV-Infected Patients on HAART

HIV Clinical Trials, 2014

Non-exercise (N-EX) questionnaires have been developed to determine maximal oxygen consumption (V... more Non-exercise (N-EX) questionnaires have been developed to determine maximal oxygen consumption (VO2max) in healthy populations. There are limited reliable and validated N-EX questionnaires for the HIV+ population that provide estimates of habitual physical activity and not VO2max. To determine how well regression equations developed previously on healthy populations, including N-EX prediction equations for VO2max and age-predicted maximal heart rates (APMHR), worked on an HIV+ population; and to develop a specific N-EX prediction equation for VO2max and APMHR for HIV+ individuals. Sixty-six HIV+ participants on stable HAART completed 4 N-EX questionnaires and performed a maximal graded exercise test. Sixty males and 6 females were included; mean (SD) age was 49.2 (8.2) years; CD4 count was 516.0 ± 253.0 cells·mm-3; and 92% had undetectable HIV PCR. Mean VO2max was 29.2 ± 7.6 (range, 14.4-49.4) mL·kg-1·min-1 Despite positive correlations with VO2max, previously published N-EX VO2max equations produced results significantly different than actual VO2 scores (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). An HIV+ specific N-EX equation was developed and produced similar mean VO2max values, R = 0.71, when compared to achieved VO2max (P = .53). HIV+ individuals tend to be sedentary and unfit, putting them at increased risk for the development of chronic diseases associated with a sedentary lifestyle. Based on the level of error associated with utilizing APMHR and N-EX VO2max equations with HIV+ individuals, neither should be used in this population for exercise prescription.

Reduced CD14 expression on classical monocytes and vascular endothelial adhesion markers independently associate with carotid artery intima media thickness in chronically HIV-1 infected adults on virologically suppressive anti-retroviral therapy

Atherosclerosis, 2014

HIV infection causes systemic immune inflammation, and increases the risk for cardiovascular (CVD... more HIV infection causes systemic immune inflammation, and increases the risk for cardiovascular (CVD) disease even among those on virologically suppressive anti-retroviral treatment (ART). We performed a biostatistical analysis and screen of candidate cellular and plasma biomarkers for association with carotid artery intima-media thickness (CIMT), independent of traditional CVD risk factors such as age, gender, systolic blood pressure (SBP), lipid levels, smoking and diabetes. We conducted a multi-stage analysis based on a cross-sectional study of CVD risk in HIV-infected subjects age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;45 years on ART for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6 months. The goal of this analysis was to identify candidate cellular and plasma biomarkers of CIMT in HIV-1 infected adults. We further sought to determine if these candidate biomarkers were independent of traditional CVD risk factors previously identified in HIV negative adults. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. Plasma soluble inflammatory mediators, cytokines and chemokines were detected. Monocytes were defined by CD14/CD16 expression, and CD8+ T-cell activation by CD38/HLA-DR expression. Subjects were a median of 49.5 years old, 87% male, had a CIMT of 0.73 mm, FRS of 6%, a median viral load of 48 copies/mL, and CD4+ T cell count of 479 cells/μL. Soluble VCAM-1, and expansion of CD14dimCD16- monocytes each associated with higher CIMT independently of age and SBP. These factors are distinct components of a shared atherogenic process; 1) vascular endothelial molecular expression and 2) vascular monocytes that enter into the vascular endothelium and promote atherosclerotic plaque.

Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status

AIDS Research and Human Retroviruses, 2008

Depletion of mitochondrial DNA (mtDNA) and mtDNA-encoded respiratory chain proteins in subcutaneo... more Depletion of mitochondrial DNA (mtDNA) and mtDNA-encoded respiratory chain proteins in subcutaneous (SC) fat from patients with HIV lipoatrophy have clearly demonstrated the role of mitochondrial dysfunction in this syndrome. Research in HIV lipoatrophy, however, has been severely hampered by the lack of a suitable surrogate marker in blood or other easily obtained clinical specimens as fat biopsies are invasive and mtDNA levels in peripheral blood mononuclear cells (PBMC) do not consistently correlate with the disease process. We used a simple, rapid, quantitative 2-site dipstick immunoassay to measure OXPHOS enzymes Complex I (CI) and Complex IV (CIV), and rtPCR to measure mtDNA in 26 matched SC fat and PBMC specimens previously banked from individuals on potent antiretroviral (ARV) therapy with HIV lipoatrophy, on similar ARV therapy without lipoatrophy, and in HIV seronegative controls. Significant correlations were found between the respective PBMC and fat levels for both CI (r = 0.442, p = 0.024) and for CIV (r = 0.507, p = 0.008). Both CI and CIV protein levels were also significantly reduced in both PBMCs and fat in lipoatrophic subjects compared to HIV seronegative controls (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 0.05), while a comparative reduction in mtDNA levels in lipoatrophic subjects was observed only in fat. We conclude that CI and CIV levels in PBMCs correlate to their respective levels in fat and may have utility as surrogate markers of mitochondrial dysfunction in lipoatrophy.

AIDS, 2010

Objective-To assess the short-term effects of extended-release niacin (ERN) on endothelial functi... more Objective-To assess the short-term effects of extended-release niacin (ERN) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol (HDL-c) levels.

Short-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients

AIDS, 2009

Ezetimibe inhibits intestinal absorption of cholesterol. Multicentered double-blind, randomized, ... more Ezetimibe inhibits intestinal absorption of cholesterol. Multicentered double-blind, randomized, placebo-controlled, crossover study to determine the short-term safety, efficacy, and tolerability of ezetimibe in combination with ongoing statin therapy in HIV-infected adults with elevated low-density lipoprotein cholesterol (LDL-C). Participants on stable HAART with fasting LDL-C at least 130 mg/dl and stable statin were randomized to ezetimibe 10 mg daily or placebo for 12 weeks followed by 4 weeks of washout and then 12 weeks with alternative study assignment. Percentage and absolute change in LDL-C (primary endpoint), total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, and high sensitivity C-reactive protein were compared. Changes in clinical symptoms and safety laboratory measurements were assessed. Forty-four participants enrolled: 70% men, median age 49 years, 43% White/Non-Hispanic, median CD4 cell count 547 cells/microl, and 95% HIV RNA less than 50 copies/ml. Median (interquartile range) percentage change in LDL-C was -20.8% (-25.4, -10.7) with ezetimibe and -0.7% (-10.3,18.6) with placebo; the median within-participant effect of ezetimibe was -14.1% (-33.0, -5.0; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Median difference in absolute LDL-C values between ezetimibe and placebo was -32 mg/dl (-58, -6, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Significant differences in within-participant effect of ezetimibe were noted for total cholesterol -18.60% (-27.22, -11.67, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), non-HDL-C -23.18% (-33.14, -14.36, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and apolipoprotein B -8.73% (-18.75, 1.99, P = 0.02). No significant changes seen in HDL-C, triglyceride, or high sensitivity C-reactive protein. Ezetimibe was well tolerated. Adverse events were similar between phases. The present short-term study found adding ezetimibe to ongoing statin therapy was well tolerated and effective in reducing LDL-C, total cholesterol, non-HDL-C, and apolipoprotein B. Adding ezetimibe to statin therapy offers reasonable treatment option for HIV-infected patients with elevated LDL-C.

To determine the impact of dietary patterns on the control of hypertension we studied the subgrou... more To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure (BP) of 140 to 159 mm Hg and/or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension (DASH) study. Participants were fed a control diet for a 3-week period and were then randomized to receive for 8 weeks either the control diet; a diet rich in fruits and vegetables, but otherwise similar to control; or a combination diet rich in fruits, vegetables, and low-fat dairy products, including whole grains, fish, poultry, and nuts, and reduced in fats, red meats, sweets, and sugar-containing beverages. Sodium intake and body weight were held constant throughout the study. The combination diet significantly reduced systolic BP (؊ ؊11.4 mm Hg, P < < .001) and diastolic BP (؊ ؊5.5 mm Hg, P < < .001). The fruits-andvegetables diet also significantly reduced systolic BP (؊ ؊7.2 mm Hg, P < < .001) and diastolic BP (؊ ؊2.8 mm Hg, P ‫؍‬ ‫؍‬ .013). The combination diet produced significantly greater BP effects (P < < .05) than the fruits-and-vegetables diet. Blood pressure changes were evident within 2 weeks of starting the intervention feeding. After the 8-week intervention period, 70% of participants eating the combination diet had a normal BP (systolic BP < < 140 and diastolic BP < < 90 mm Hg) compared with 45% on the fruits-and-vegetables diet and 23% on the control diet. In patients with hypertension, the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension. Am J Hypertens 2000;13:949 -955