Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART.

INTRODUCTION: Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular ageing and cardiovascular disease (CVD). While delayed time to initiation of ART has been linked to worse cardiovascular outcomes, the effect of ART initiation during acute infection on these outcomes is not well understood. METHODS: Participants were enrolled from the SEARCH010/RV254 acute HIV (AHI) and HIV-NAT chronic HIV (CHI) cohorts in Thailand. Participants with 6-year follow-up and viral suppression (viral load < 50 copies/µL) at follow-up were included. Both unmatched cohorts and age and gender-matched cohorts were analysed. Demographics, HIV laboratories, and cardiovascular risk factors from enrolment and 6-year follow-up were obtained from electronic records. Framingham Risk Score (FRS), vascular age (VA), vascular age deviation (VAD), and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated from previously published equations. Vascular outcomes in AHI and CHI cohorts were compared, and univariable and multivariable linear regression analyses were used to investigate risk factors associated with worse vascular scores. RESULTS: In all, 373 AHI participants and 608 CHI participants were identified. AHI participants were of younger age, had a higher prevalence of syphilis and a lower prevalence of prior hepatitis B, tuberculosis, diabetes, and hypertension. Higher CD4 T-cell and lower CD8 T-cell counts were seen in the AHI cohort at enrolment and 6-year follow-up. In all participants, the AHI cohort had a lower median FRS (p < 0.001) and VA (p < 0.001), but higher VAD (p < 0.001). However, in matched cohorts, no differences were found in FRS-based outcomes. In all participants, higher VAD after 6 years of ART was associated with higher body mass index (p < 0.001) and higher CD4 count (p < 0.001), which persisted in multivariable analysis. When FRS components were analysed individually, CD4 count was associated only with male sex and cholesterol. CONCLUSIONS: We did not identify differences in FRS-based vascular outcomes at 6 years in matched cohorts of participants who started ART during AHI versus CHI. We identified a correlation between higher CD4 count and worse FRS-based vascular outcomes, which may be driven by underlying metabolic risk factors. Further study is needed to confirm these findings and evaluate underlying mechanisms.

Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis With Liver Fibrosis as Predictors of New-Onset Diabetes Mellitus in People With HIV: A Longitudinal Cohort Study.

BACKGROUND: We investigated the association between nonalcoholic fatty liver disease (NAFLD) plus or minus a concurrent diagnosis of nonalcoholic steatohepatitis (NASH) and incident diabetes mellitus (DM) and the risk factors associated with NAFLD or NASH development. METHODS: In this prospective study, we analyzed people with human immunodeficiency virus (HIV; PWH) aged ≥18 years without excessive alcohol consumption or hepatitis coinfections. NAFLD was defined as controlled attenuation parameter ≥248 dB/m, whereas NASH with significant disease activity and liver fibrosis was defined as a FibroScan-AST score ≥0.67. Cox proportional hazard regression was used to investigate the association between NAFLD with or without NASH and new-onset DM. RESULTS: Of 847 PWH, the median age at baseline was 45 years (interquartile range, 38-51; 43% female). Baseline NAFLD was associated with 2.8-fold higher risk of new-onset DM after adjusting for age, sex, family history of DM, antiretroviral therapy duration, smoking, statin use, stavudine/didanosine/zidovudine exposure, time-updated body mass index, hypertension, and dyslipidemia. Combined NAFLD and NASH at baseline had 3.1-fold higher new-onset DM risk. In separate analyses, baseline DM did not predict progression to NAFLD or NASH, but tenofovir alafenamide use was associated with an increased risk of NAFLD (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.02-4.02) or NASH development (2.31; 95% CI, 1.12-5.11). CONCLUSIONS: NAFLD alone or combined with NASH strongly predicts new-onset DM. This highlights the need for systematic risk assessments and management of NAFLD/NASH, as it may contribute to metabolic complications such as DM and subsequent cardiovascular diseases in PWH.

Impact of steatotic liver disease and non-alcoholic steatohepatitis on cognitive impairment in people living with HIV: A cross-sectional study.

INTRODUCTION: The link between fatty liver diseases and cognitive impairment among people living with HIV (PLWH) remains unclear. We investigated the association of steatotic liver disease (SLD), advanced liver fibrosis and non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis with cognitive impairment in PLWH. METHODS: Cognitive performance was assessed for PLWH aged ≥50 years on stable antiretroviral therapy (ART) with the Thai-validated version of the Montreal Cognitive Assessment (MoCA), and a cut-off of <25/30 was used to define cognitive impairment. SLD and NASH with significant activity and liver fibrosis were defined as having a controlled attenuation parameter value ≥248 dB/m and a FibroScan-AST (FAST) score ≥0.67, respectively. Multivariable logistic regression was employed to investigate the association of cognitive impairment with SLD or NASH. RESULTS: Of the 319 PLWH (63.3% male and 98% had HIV-1 RNA ≤50 copies/mL) included, 74 (38%) had SLD. NASH with significant activity and liver fibrosis was present in 66 (20.1%) participants. Some 192 (60.2%) participants had cognitive impairment. In a multivariable analysis, NASH with significant activity and liver fibrosis was significantly associated with cognitive impairment (adjusted odds ratio [aOR] 2.01, 95% CI 1.02-3.98, p = 0.04), after adjusting for HIV-related parameters, age, sex, body mass index, employment status, education, income level, smoking, alcohol use, diabetes mellitus, hypertension and HIV-related parameters. The association of a lone diagnosis of SLD and cognitive impairment was not statistically significant. CONCLUSIONS: NASH with significant activity and liver fibrosis was associated with lower cognitive performance, even after controlling for demographics and HIV disease parameters. Additional research is needed to better understand the underlying mechanisms.

Metabolic-Associated Fatty Liver Disease (MAFLD) is associated with immune activation, increased epicardial fat volume, and steatohepatitis among people with HIV in a Thai cohort.

INTRODUCTION: A change in terminology from fatty liver disease to metabolic-associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. METHODS: We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10-year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan-aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. RESULTS: The median age was 54 years (interquartile range [IQR] 52-60) and current CD4 count was 613 (IQR 467-804) cells/mm3 . A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non-alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6-6.6), and similar associations were also observed among different MAFLD categories. CONCLUSIONS: The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease.

Association of Phenotypic Aging Marker with comorbidities, frailty and inflammatory markers in people living with HIV.

BACKGROUND: Aging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI. METHODS: In a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty. RESULTS: Among 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (- 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03-2.73]), current smoking (2.74 [1.30-5.79]), diabetes mellitus (2.97 [1.48-5.99]), hypertension (1.67 [1.02-2.72]), frailty (3.82 [1.33-10.93]), and higher IL-6 levels (1.09 [1.04-1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66-0.85] vs. 0.65 [0.55-0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant. CONCLUSIONS: While PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group.

Large transmission cluster of acute hepatitis C identified among HIV-positive men who have sex with men in Bangkok, Thailand.

A rapidly emerging and highly concentrated hepatitis C virus (HCV) outbreak has recently been observed among both acute and chronic HIV-positive men who have sex with men (MSM) in Bangkok, Thailand. NS5B regions of the HCV genome were amplified using nested PCR and sequenced. Phylogenetic inference was constructed by Maximum Likelihood methods and clusters were identified with support and genetic distance thresholds of 85% and of 4.5%. Forty-eight (25 acute HIV and 23 chronic HIV) MSM with incident HCV infection were included in the analysis. HCV genotype (GT) was 85% GT 1a and 15% GT 3a or 3b. Median age at HCV diagnosis was 34 (interquartile range, 28-41) years. 83.3% (40/48) had history of syphilis infection and 36% (16/44) reported crystal methamphetamine use. Only 2 (4%) reported ever injecting drugs, both crystal methamphetamine. In the phylogenetic clustering analysis, 83% belonged to one of two clusters: one large (75%) and one small (8%) cluster. All clusters were GT 1a. MSM with acute HIV infection were more likely to be in a cluster (92%) than those with chronic infection (74%). HCV screening should be regularly performed for MSM in ART clinics, and offering direct-acting antiviral agents to all MSM with HCV infection might contain the HCV epidemic from expanding further.

Efficacy and improvement of lipid profile after switching to rilpivirine in resource limited setting: real life clinical practice.

BACKGROUND: Long-term success of cART is possible if the regimen is convenient and less-toxic. This study assessed the efficacy and safety of switching from a first-line NNRTI or boosted PI-based regimens to RPV-based regimens among virologically suppressed participants in resource-limited setting (RLS). METHODS: This is a prospective cohort study. Participants with plasma HIV-RNA < 50 copies/mL receiving cART were switched from a PI- or NNRTI-based, to a RPV-based regimen between January 2011 and April 2018. The primary endpoint was the proportion of patients with plasma HIV-1 RNA level < 50 copies/mL after 12 months of RPV. The secondary endpoint was the virological response at 24 months and safety endpoint (change in lipid profiles and kidney function from baseline to 12 months). RESULTS: A total of 320 participants were enrolled into the study. The rationale for switching to RPV was based on toxicity of the current regimen (57%) or desire to simplify cART (41%). Totally, 177 (55%) and 143 (45%) participants were on NNRTI and boosted PI, respectively, prior to switching to RPV. After 12 months, 298 (93%) participants maintained virological suppression. There were significant improvements in the lipid parameters: TC (- 21 (IQR - 47 to 1) mg/dL; p < 0.001), LDL (- 14 (IQR - 37 to 11) mg/dL; p < 0.001) and TG (- 22 (IQR - 74 to 10) mg/dL; p < 0.001). Also, there was a small but statistically significant decrease in eGFR (- 4.3 (IQR - 12 to 1.1) mL/min per 1.73m2; p < 0.001). CONCLUSIONS: In RLS where integrase inhibitors are not affordable, RPV-based regimens are a good alternative option for PLHIV who cannot tolerate first-line NNRTI or boosted PI regimen, without prior NNRTI/PI resistance. Trial registration HIV-NAT 006 cohort, clinical trial number: NCT00411983.

Use of copper intrauterine device is not associated with higher bacterial vaginosis prevalence in Thai HIV-positive women.

The study assessed and compared bacterial vaginosis (BV) prevalence in Thai women in reproductive age in four study groups - group 1, HIV-positive with copper intrauterine device (Cu-IUD); group 2, HIV-positive without Cu-IUD; group 3, HIV-negative with Cu-IUD; and group 4, HIV-negative without Cu-IUD. We conducted a cross-sectional study. BV prevalence was assessed by Nugent score and Amsel criteria. Descriptive statistics was used to present baseline characteristics; kwallis rank test - to compare variables between the four groups; logistic regression - to assess factors, related to BV prevalence. The analysis included 137 women in the four study groups with a median age of 39 years. Median BV prevalence by Nugent score was 45%, intermediate vaginal flora - 7% and normal vaginal flora - 48%. There was no statistically significant difference in the BV prevalence between the four study groups, p = 0.711. Threefold lower BV prevalence was found, assessed by Amsel criteria compared to Nugent score. Women with body mass index (BMI) < 20 had higher probability to have BV or intermediate vaginal flora, OR = 3.11, 95% CI (1.2-8.6), p = 0.025. The study found a high BV prevalence in the four study groups, related neither to HIV status, nor to Cu-IUD use. BV prevalence was associated only with low BMI. Thus, Cu-IUD could be a good contraceptive choice for HIV-positive women. Research in defining normal vaginal microbiota and improve diagnostic methods for BV should continue.

CD4/CD8 ratio normalization rates and low ratio as prognostic marker for non-AIDS defining events among long-term virologically suppressed people living with HIV.

BACKGROUND: Immune restoration is often incomplete after ART in HIV patients, both quantitatively and qualitatively. We studied the incidence and probability of CD4/CD8 normalization in an adult Thai HIV cohort and explored the predictive value of the ratio for developing of non-AIDS defining events (NAEs). METHODS: We analyzed data from HIV-infected Thai adults between 1996 and 2017 in the HIV-NAT 006 prospective long-term cohort in Bangkok, Thailand. Normalization was defined as CD4/CD8 ratio ≥ 1 on two consecutive visits, and normalization probability was calculated using the Kaplan-Meier method. NAEs were a composite endpoint including cardiovascular or cerebrovascular diseases, chronic kidney diseases, non-AIDS defining malignancies and death. Multivariate Cox regression was used to evaluate demographic, disease and treatment characteristics associated with CD4/CD8 ratio normalization and NAEs. RESULTS: A total of 800 ART-naïve patients with baseline CD4/CD8 ratio of < 0.8 who started combination ART, and had sustained virological suppression were enrolled. Participants were on ART for a median of 8.9 years and virologically suppressed for 6.1 years. The probabilities of CD4/CD8 normalization at 2, 5 and 10 years after virological suppression were 5.1%, 18.6% and 39.1%, respectively. Factors associated with normalization in multivariate analysis were female sex (hazard ratio [HR]: 2.47, 95% CI 1.71-3.56, p < 0.001) and baseline CD4 counts ≥ 350 cells/mm3 (HR: 3.62, 95% CI 2.36-5.55), p < 0.001) vs. < 200 cells/mm3 as reference. The second analysis explored the predictive value of CD4/CD8 ratio for NAEs. Older age (HR: 1.09, 95% CI 1.05-1.13, p < 0.01) and current CD4/CD8 ratio < 0.3 (HR: 3.02, 95% CI 1.27-7.21, p = 0.01) or between 0.3 and 0.45 (HR: 2.03, 95% CI 1.03-3.98, p = 0.04) vs. > 0.45 were independently associated with higher risk of progression to NAEs in the multivariate analysis. CONCLUSIONS: Our findings showed that complete immune recovery is uncommon in an Asian setting and earlier ART initiation at higher CD4 counts may have increased the ratio sooner. The findings demonstrate the use of CD4/CD8 ratio as a prognostic marker for clinical progression of NAEs. Trial registration HIV-NAT 006 cohort, clinical trial number: NCT00411983.

Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: role of vitamin D levels.

BACKGROUND AND AIM: Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. METHODS: Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. RESULTS: A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. CONCLUSIONS: HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings.

Association between lymphocyte and monocyte subsets and cognition in children with HIV.

BACKGROUND: This study assesses the relationships between lymphocyte and monocyte subsets and intelligence quotient (IQ) scores in antiretroviral therapy (ART)-naive, HIV-infected Thai children without advanced HIV disease. FINDINGS: Sixty-seven ART-naive Thai children with CD4 between 15-24% underwent cognitive testing by Weschler intelligence scale and had 13 cell subsets performed by flow cytometry including naive, memory and activated subsets of CD4+ and CD8+ T cells, activated and perivascular monocytes and B cells. Regression modelling with log10 cell count and cell percentage transformation was performed.Median age (IQR) was 9 (7-10) years, 33% were male, CDC stages N:A:B were 1:67:31%, median CD4% and count (IQR) were 21 (18-24)%, 597 (424-801) cells/mm3 and HIV RNA (IQR) was 4.6 (4.1-4.9) log10 copies/ml. Most (82%) lived at home, 45% had a biological parent as their primary caregiver, and 26 (49%) had low family income. The mean (SD) scores were 75 (13) for full scale IQ (FIQ), 73 (12) for verbal IQ (VIQ) and 80 (14) for performance IQ (PIQ). Adjusted multivariate regression analysis showed significant negative associations between B cell counts and FIQ, VIQ and PIQ (p < 0.01 for all); similar associations were found for B cell percentages (p < 0.05 for all). CONCLUSIONS: High B cell counts and percentages were strongly associated with poorer FIQ, VIQ and PIQ scores. Prospective, long-term assessment of cell subsets and determination of relevant B cell subpopulations could help further elucidate associations between lymphocyte subsets and neurocognitive development.

Phase II prefusion non-stabilised Covid-19 mRNA vaccine randomised study.

ChulaCov19 mRNA vaccine demonstrated promising phase 1 results. Healthy adults aged 18-59 years were double-blind randomised 4:1 to receive two intramuscular doses of ChulaCov19 50 µg or placebo. Primary endpoints were safety and microneutralization antibody against-wild-type (Micro-VNT50) at day 50. One hundred fifty adults with median (IQR) age 37 (30-46) years were randomised. ChulaCov19 was well tolerated, and most adverse events were mild to moderate and temporary. Geometric mean titres (GMT) of neutralizing titre against wild-type for ChulaCov19 on day 50 were 1367 IU/mL. T-cell IFN-γ-ELISpot showed the highest responses at one week (Day29) after dose 2 then gradually declined. ChulaCov19 50 µg is well tolerated and elicited high neutralizing antibodies and strong T-cell responses in healthy adults.Trial registration number: ClinicalTrials.gov Identifier NCT04566276, 28/09/2020.

Cytomegalovirus viremia in Thai HIV-infected patients on antiretroviral therapy: prevalence and associated mortality.

BACKGROUND: Prevalence and risk factors of cytomegalovirus (CMV) viremia in patients infected with human immunodeficiency virus (HIV) starting antiretroviral therapy (ART) in developing countries are understudied. METHODS: We measured CMV DNA in stored plasma specimens of 293 Thai HIV patients starting ART at CD4 counts <200 cells/mm(3). We examined Cox proportional hazard ratios (HRs) of 24 months mortality and new AIDS-defining illness (ADI). RESULTS: Of 293 patients, 159 (54.3%) were male. The median age was 33 years. The median baseline CD4 count was 82 cells/mm(3), and the median HIV-1 RNA was 4.9 log10 copies/mL. In total, 273 (93.2%) patients started potent combination ART, and 20 (6.8%) started dual nucleoside reverse transcriptase inhibitor (NRTI) therapy. CMV DNA was detected in 77 of 293 patients (26.3%) at baseline, and 9 of 199 patients with available specimen (4.5%) after 6 months of ART. The median CMV DNA was 548 copies/mL (interquartile range [IQR], 129-3849) at baseline and 114 copies/mL (IQR, 75-1099) at 6 months. In univariate analysis, death was associated with baseline CDC stage C, hemoglobin <10 g/dL, lower CD4 count, and CMV viremia. In multivariate analysis, only CMV DNA >500 copies/mL was significantly associated with mortality (HR: 7.28; 95% CI, 1.32-40.29, P = .023). CD4 count was the only variable associated with new ADI (HR: 0.70 per 50 CD4 cells increase; 95% CI, .49-.997, P = .048). CONCLUSIONS: In these Thai patients with advanced HIV disease, CMV viremia was frequent, and CMV DNA >500 copies/mL predicted increased mortality despite ART initiation. This calls for increased attention to screening of active CMV infection in advanced HIV patients in developing countries. Trials assessing preemptive anti-CMV therapy may be warranted.

Immunoglobulin values in healthy Thai children aged ≤ 24 months determined by nephelometry.

BACKGROUND: Variation of normal immunoglobulin (Ig) levels between different genetic and environment factors has been studied. Although antibody deficiency diseases can start from infancy, data of Ig reference levels in children aged ≤24 months are still limited, especially in Asian children. PURPOSE: The aim of this study was to determine serum IgG, IgA, IgM, and IgG subclasses in healthy Thai children from the newborn period to age 24 months. METHODS: Serum samples were collected from healthy Thai children age <1-24 months to measured serum IgG, IgA, IgM, and IgG subclasses by nephelometry. RESULTS: Of the 100 infants, 44% were female with a median (range) age of 13 (0.3-24) months. The geometric mean IgG was 803 mg/dL, IgA 36 mg/dL, and IgM 102 mg/dL. The mean IgG1 was 646 mg/dL, IgG2 127 mg/dL, IgG3 45 mg/dL, and IgG4 17 mg/dL. The average ratios of IgG subclass 1:2:3:4 were 77:15:6:2%. No significant differences in each immunoglobulin isotype between genders were found. Our mean IgG level was slightly lower than that in healthy Thai children, measured by radial diffusion method but not significant except 1-3 months (p = 0.016). However, the mean IgG level in our study was higher than that reported by radial diffusion in healthy US children (p <0.001). CONCLUSIONS: This study illustrated the importance of having normal Ig values from age- and ethnically-matched controls by high precision nephelometric assay in order to appropriately diagnose immunologic disorders in Asian infants.

High-Sensitivity Troponins and Subclinical Coronary Atherosclerosis Evaluated by Coronary Calcium Score Among Older Asians Living With Well-Controlled Human Immunodeficiency Virus.

Background: Elevated levels of high-sensitivity cardiac troponin (hs-cTn) are suggestive of myocardial cell injury and coronary artery disease. We explored the association between hs-cTn and subclinical arteriosclerosis using coronary artery calcification (CAC) scoring among 337 virally suppressed patients with human immunodeficiency virus (HIV) who were ≥50 years old and without evidence of known coronary artery disease. Methods: Noncontrast cardiac computed tomography and blood sampling for hs-cTn, both subunit I (hs-cTnI) and subunit T (hs-cTnT), were performed. The relationship between CAC (Agatston score) and serum hs-cTn levels was analyzed using Spearman correlation and logistic regression models. Results: The patients, of whom 62% were male, had a median age of 54 years and had been on antiretroviral therapy for a median of 16 years; the CAC score was >0 in 50% of patients and ≥100 in 16%. Both hs-cTn concentrations were positively correlated with the Agatston score, with correlation coefficients of 0.28 and 0.27 (P < .001) for hs-cTnI and hs-cTnT, respectively. hs-cTnI and hs-cTnT concentrations of ≥4 and ≥5.3 pg/mL, respectively, provided the best performance for discriminating patients with Agatston scores ≥100, with a sensitivity and specificity of 76% and 60%, respectively, for hs-cTnI and 70% and 50% for hs-cTnT. In multivariable logistic regression analysis, each log unit increase in hs-cTnI level was independently associated with increased odds of having an Agatston score ≥100 (odds ratio, 2.83 [95% confidence interval, 1.69-4.75]; P <.001). Although not an independent predictor, hs-cTnT was also associated with an increased odds of having an Agatston score ≥100 (odds ratio, 1.58 [95% confidence interval, .92-2.73]; P = .10). Conclusions: Among Asians aged ≥50 years with well-controlled HIV infection and without established cardiovascular disease, 50% had subclinical arteriosclerosis. Increasing hs-cTnI and hs-cTnT concentrations were associated with an increased risk of severe subclinical arteriosclerosis, and hs-cTn may be a potential biomarker to detect severe subclinical arteriosclerosis.

Nephelometry determined serum immunoglobulin isotypes in healthy Thai children aged 2-15 years.

Knowledge of what constitute normal serum immunoglobulin (Ig) concentrations are important for the diagnosis of immunologic disorders. Data on normal Ig evaluated by nephelometry are limited in healthy Asian children, none being available for Thai children. One hundred and forty-eight healthy Thai children aged 2-15 years were tested for serum immunoglobulins G, A, M, G1, G2, G3, and G4 (Ig G, A, M, G1, G2, G3, and G4) by nephelometry. Sixty-three percent were girls of median interquartile range age 6.9 (4.8-9.7) years. The geometric means for each Ig were summarized and categorized by age. Statistical analyses were used to compare Igs between sexes and age groups, and to compare IgG in this study with data from other published studies. The average ratios of IgG subclasses/IgG for Ig G1:2:3:4 were 66:22:5:7%. IgG, IgA, IgG2, and IgG3 concentrations showed a gradual increase with increasing age. There were no significant sex differences for any immunoglobulin isotype (P= 0.971). Our mean IgG concentration was lower than that measured by the radial diffusion method in healthy Thai children (P < 0.05). In all age groups, the mean IgG concentration in our study was significantly higher than that reported in Turkish and USA children, evaluated by the nephelometric and radial diffusion techniques, respectively (both P < 0.001). This study provides information about normal Ig concentrations measured by nephelometry in healthy Asian children and illustrates the importance of ascertaining normal Ig values for age- and ethnic-matched controls using the same assay to diagnose immunologic disorders correctly.

Correlation Between Polypharmacy and Frailty Among Thai Older Persons Living with HIV.

Polypharmacy and frailty are correlated in Persons Living with HIV (PLWH) in the United States, but little is known about their correlation in resource-limited settings. Our cross-section study evaluated the correlation between polypharmacy and frailty among Thai 324 virally suppressed PLWH and 132 uninfected patients aged ≥50 between March 2016 and April 2017. The primary predictor was the number of patient-reported non-antiretroviral therapy (ART) medications. The outcome was having additional domain of the five Fried frailty phenotype domains (0 = normal, 1-2 = prefrail, >3 = frail). Most participants were male (63% PLWH, 67% uninfected) with few comorbidities (1.4 PLWH, 0.9 uninfected) and small median number of non-ART medications (2 PLWH, 1 uninfected). Frailty was uncommon (8.6% PLWH, 3.8% uninfected). Each additional non-ART medication correlated with 6% increased likelihood of having additional frailty domain among PLWH (95% CI: 0.002-0.11, p = .04) but not statistically significant among the uninfected. The association between polypharmacy and frailty is more pronounced in Thai PLWH than in participants without HIV. Further study is warranted to confirm this association in other resource-limited settings and explore potential deprescribing practices.

Deterioration of Nutritional Status and Its Negative Association with Depression Among Older HIV-Infected Asian Population: A Four-Year Longitudinal Study.

There is limited evidence about the long-term changes in nutritional status among the elderly people living with human immunodeficiency virus (PLWH). We aimed to investigate the changes in nutritional status and related factors over 4 years in the elderly PLWH. The longitudinal study was conducted prospectively among 250 PLWH, 50 years of age and older, receiving antiretroviral therapy (ART). The Mini Nutritional Assessment (MNA) and Thai Depression Scale (TDS) to assess nutritional status and depression, respectively, were performed at the outpatient clinic both at baseline and 4-year follow-up. Majority were male (60.8%) with median age of 58 years. The median CD4 was 612.5 cells/mm3 and 98% had HIV RNA <50 copies/mL. Median duration of ART was 20 years. Median body mass index was 23.1 kg/m2. The most common ART were rilpivirine (45.2%) and dolutegravir (18.8%). Fifty-one patients (20.4%) deteriorated in nutritional status and mean MNA scores declined (25.8 vs. 24.8, p < .001) at follow-up period. In multivariate analysis, high TDS scores (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.17-1.52), polypharmacy (OR, 1.35; 95% CI, 1.10-1.65), and high-density lipoprotein cholesterol (HDL-C) levels (OR, 1.04; 95% CI, 1.01-1.07) were associated factors of deterioration in nutritional status. In this 4-year longitudinal follow-up, 20% of the aging PLWH have deterioration of nutritional status. High TDS scores (depression), polypharmacy, and high HDL-C were significantly associated with declining nutritional status. Our findings highlight the importance of screening and monitoring nutritional and depression status in routine HIV treatment and care for geriatric HIV-infected population.

Higher epicardial fat in older adults living with HIV with viral suppression and relationship with liver steatosis, coronary calcium and cardiometabolic risks.

OBJECTIVES: HIV infection is associated with ectopic fat deposition, which leads to chronic inflammation and cardiometabolic dysregulation. We assessed the epicardial adipose tissue (EAT) volume and its associated factors among people with HIV (PWH). DESIGN: A cross-sectional study. METHODS: We conducted a cross-sectional study among PWH aged at least 50 years and age-matched and sex-matched HIV-negative older individuals in Bangkok, Thailand. Participants underwent a noncontrast, cardiac computed tomography (CT) scan to assess coronary artery calcium (CAC) score and EAT between March 2016 and June 2017. Multivariate linear regression analyses were used to investigate HIV-related factors, cardiac and metabolic markers associated with EAT volume. RESULTS: Median age was 55 years [interquartile range (IQR) 52-60] and 63% were men. Median duration of antiretroviral therapy (ART) was 16 years with 97% had HIV-1 RNA less than 50 copies/ml and median CD4 + cell count of 617 cells/µl. Median EAT volume was significantly higher in PWH [99 (IQR 75-122) cm 3 ] than HIV-negative individuals [93 (IQR 69-117) cm 3 ], P  = 0.022. In adjusted model, factors associated with EAT volume included male sex ( P  = 0.045), older age ( P  < 0.001), abnormal waist circumference ( P  < 0.001) and HOMA-IR ( P  = 0.01). In addition, higher CAC score was independently associated with EAT volume. Higher mean EAT volume was seen in PWH with severe liver steatosis than those without steatosis ( P  = 0.018). In adjusted PWH-only model, duration of HIV was significantly associated with higher EAT volume ( P  = 0.028). CONCLUSION: In an aging cohort, PWH had higher EAT volume than HIV-negative controls. EAT was also independently associated with central fat accumulation, insulin resistance, liver steatosis and CAC score.

Bone mineral density among virologically suppressed Asians older than 50 years old living with and without HIV: A cross-sectional study.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15-21) years in men and 18 (IQR 15-21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5-8.9) years in men and 8.2 (IQR 6.1-10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983.