Publications by authors named "Tanakorn Apornpong"

31 Publications

Antiretroviral Hair Levels, Self-Reported Adherence and Virologic Failure in Second-Line Regimen Patients in Resource-Limited Settings.

AIDS 2021 Apr 6. Epub 2021 Apr 6.

HIV-NAT, TRCARC, Bangkok, Thailand Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil Harvard T.H. Chan School of Public Health, Boston, MA,USA Biostatistics Excellence Centre, Bangkok, Thailand The Kirby Institute, UNSW, Sydney, Australia University of Nebraska Medical Center, Omaha, USA Chulalongkorn University, Bangkok, Thailand Division of AIDS NIAID, NIH, Bethesda, USA University of Pennsylvania, PA,USA Social & Scientific Systems, Silver Spring, USA BARC-SA and Lancet Laboratories, South Africa Clinical HIV Research Unit, Helen Joseph Hospital, University of the Witwatersrand, Johannesburg, South Africa Kamuzu Central Hospital, Lilongwe, Malawi Durban International CRS, Durban, South Africa Hospital Nossa Senhora da Conceicao CRS, Rio Grande do Sul, Brazil Emory University, Atlanta, USA Frontier Science & Technology Research Foundation, Inc., Amherst, United States Family Centre for Research with Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa Research Institute for Health Sciences, Chiang Mai, Thailand Kamuzu Central Hospital, Lilongwe, Malawi CART, Clinical Research Site, VHS Infection Disease Medical Centre, Chennai, India Case Western Reserve University, Cleveland, USA University of Washington, Seattle, USA University of California, San Francisco, USA.

Objective: To evaluate associations between hair antiretroviral (ARV) hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes.

Design: Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line PI-based ART, but were susceptible to ≥1 NRTI and their PI, and continued taking their PI-based regimen.

Methods: ARV hair concentrations participants taking 2 NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography-tandem-mass-spectrometry assays. Participants self-reported percentage of doses taken in the previous month; virologic failure (VF) was confirmed HIV-1 RNA≥1000 copies/mL at week 24 or 48.

Results: From 181 participants with hair samples, (61% female median age: 39y; CD4 count: 167 cells/uL; HIV-1 RNA: 18,648 copies/mL), 91 (50%) experienced VF at either visit. At 24 weeks, median hair concentrations were 2.95 (IQR 0.49-4.60) ng/mg for atazanavir, 2.64 (IQR 0.73-7.16) for lopinavir, and 0.44 (IQR 0.11-0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with VF, the hazard ratio (HR) (95%CI) for ATV, LPV and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27) respectively.

Conclusions: PI hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of 2nd-line treatment failure in need of interventions.
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http://dx.doi.org/10.1097/QAD.0000000000002901DOI Listing
April 2021

Characteristics of suboptimal immune response after initiating antiretroviral therapy among people living with HIV with a pre-treatment CD4 T cell count <200 ​cells/mm in Thailand.

J Virus Erad 2020 Sep 19;6(3):100005. Epub 2020 Jul 19.

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: Complete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais.

Methods: Treatment-naïve participants (n ​= ​375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level ​< ​400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4 T cell count <200 ​cells/mm for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n ​= ​17) and non-SIR (n ​= ​24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated.

Results: Among 375 participants with pre-ART CD4 T cell counts < 200 ​cells/mm, the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count ≤100 ​cells/mm (adjusted odds ratio [aOR] 9.45, 95% CI 2.92-30.61, p ​< ​0.001), older age (aOR 1.07, 95% CI 1.01-1.13, p ​= ​0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21-0.59, p ​< ​0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases ​= ​17, controls ​= ​24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p ​= ​0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log ​pg/mL, p ​= ​0.04), lower CD8 T cell counts (mean, 514 vs. 876, p ​= ​0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p ​= ​0.01) and higher expression of PD1 on CD8 T cells (74.2% vs. 65.1%, p ​= ​0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation.

Conclusions: Nearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.
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http://dx.doi.org/10.1016/j.jve.2020.100005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646671PMC
September 2020

Echocardiographic Findings Among Virally Suppressed HIV-Infected Aging Asians Compared with HIV-Negative Individuals.

J Acquir Immune Defic Syndr 2020 11;85(3):379-386

The HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Objectives: Prevalence of cardiovascular disease increases with age. Little is known about the prevalence and risk factors for echocardiographic abnormalities among older people living with HIV (PLHIV) from Asia.

Design: A cross-sectional study was conducted among PLHIV aged >50 years (N = 298) on antiretroviral treatment (ART) and HIV-negative controls (N = 100) frequency matched by sex and age in Thailand.

Methods: All participants underwent standard 2-dimensional transthoracic echocardiography performed by trained cardiologists who were blinded to the participant's care and HIV status. Logistic regression was used to examine the association between cardiac abnormalities and risk factors.

Results: The median age was 54.7 years (60.8% men) with 37.2% having hypertension and 16.6% having diabetes mellitus. PLHIV was on ART for a median of 16.2 years with current CD4 cell counts of 616 cells per cubic millimeter. Echocardiogram abnormalities did not differ among PLHIV (55%) and the controls (60%). The major abnormalities in PLHIV were following: left ventricular (LV) hypertrophy: 37% men and 42.2% women, LV systolic dysfunction (0.7%), diastolic dysfunction (24.2%), and pulmonary hypertension (3.9%). From the multivariate analyses in PLHIV, being aged >60 years was independently associated with diastolic dysfunction, whereas female sex and left atrial volume index of >34 mL/m were associated with pulmonary hypertension (P < 0.05). None of the ART was significantly associated with any major echocardiographic abnormalities.

Conclusions: In this long-term, well-suppressed, older, Asian PLHIV cohort, the prevalence of asymptomatic LV systolic dysfunction and pulmonary hypertension were relatively low, whereas the diastolic dysfunction and LV hypertrophy were common. Echocardiographic findings did not differ between PLHIV and HIV-uninfected controls.
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http://dx.doi.org/10.1097/QAI.0000000000002456DOI Listing
November 2020

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

Liver Int 2020 09 20;40(9):2104-2109. Epub 2020 Jul 20.

Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, 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.
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http://dx.doi.org/10.1111/liv.14578DOI Listing
September 2020

Bone mineral density changes among people living with HIV who have started with TDF-containing regimen: A five-year prospective study.

PLoS One 2020 25;15(3):e0230368. Epub 2020 Mar 25.

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p<0.001 for LS, p = 0.006 for TH and p = 0.02 for FN). HIV-positive status and on TDF-containing regimen was independently associated with BMD loss ≥5% at month 60 (adjusted odds ratio [aOR] 7.0, 95% confidence interval [95%CI] 2.3-21.0, P = 0.001 for LS; aOR 4.9, 95%CI 1.7-14.3, P = 0.003 for TH and aOR 4.3, 95%CI 1.6-11.2, P = 0.003 for FN) compared to HIV-uninfected individuals. In a multivariate model for PLHIV only, TDF use (vs. non-TDF, P = 0.005) and pre-treatment CD4+ count <350 cells/mm3 (vs. ≥350 cells/mm3, P = 0.02) were independently associated with ≥5% BMD loss in TH at month 60. Treatment-naïve PLHIV initiating treatment with TDF-containing regimen have higher BMD loss in a Thai cohort. TDF use and low pre-treatment CD4 count were independently associated with BMD loss at month 60 at TH. Earlier treatment initiation and interventions to prevent bone loss could improve skeletal health among PLHIV. Clinicaltrials.gov: NCT01634607.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230368PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094833PMC
June 2020

CD4/CD8 Ratio Recovery of Children and Adolescents Living With HIV With Virological Suppression: A Prospective Cohort Study.

J Pediatric Infect Dis Soc 2021 Mar;10(2):88-96

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: There are limited data on immune restoration of young adults living with virologically suppressed human immunodeficiency virus (HIV). We investigated recovery rates of CD4/CD8 ratio among Thai children and adolescents after they initiated combination antiretroviral therapy (cART).

Methods: Children and adolescents who started cART at age of ≥ 5 years were eligible in this study if they achieved HIV RNA < 50 copies/mL and had a CD4/CD8 ratio < 0.8 at the time of virological suppression. Normalization of CD4/CD8 ratio was defined as 2 consecutive values ≥ 1. Using group-based trajectory analysis, low- and high-recovery groups were identified in terms of CD4/CD8 ratio recovery.

Results: One hundred thirty-eight children and adolescents (101 perinatally infected and 37 behaviorally infected) with median age of 10.6 years at cART treatment initiation were included. After 559 person-years of follow-up (PYFU), overall incidence rate of CD4/CD8 ratio normalization was 4.1 (95% confidence interval, 2.7-6.2) per 100 PYFU. The probabilities of normalization at 2, 5, and 10 years after HIV suppression were 5.2%, 22.6%, and 35.6%, respectively. The low-recovery group had lower median pre-cART CD4 count (146 vs 304 cells/μL, P = .01), pre-cART CD4/CD8 ratio (0.15 vs 0.23, P = .03) and at first viral suppression (0.38 vs 0.65, P = .0001), compared to the high-recovery group.

Conclusions: Less than half of children and adolescents living with HIV on cART with viral suppression had CD4/CD8 ratio normalization. Those with older age at cART initiation, lower pre-cART CD4 count, or CD4/CD8 ratio had slower ratio recovery. Long-term prognoses such as ongoing immune activation and clinical outcomes among children and adolescents on suppressive cART without CD4/CD8 ratio normalization need to be further investigated.
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http://dx.doi.org/10.1093/jpids/piaa020DOI Listing
March 2021

Higher Proportion of Abnormal Nutritional Status Among Well-Suppressed HIV-Infected Elderly Asians Compared to HIV-Negative Individuals.

AIDS Res Hum Retroviruses 2020 07 25;36(7):590-596. Epub 2020 Mar 25.

HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Older adults face physiological, psychological, social, and economic changes, which may impair nutritional status, making the body vulnerable to illness and adverse clinical outcomes. Little is known regarding the nutritional status among elderly people living with HIV (PLHIV). We aimed to study the prevalence of malnutrition and the associated factors in a Thai aging cohort. A cross-sectional study was conducted among PLHIV >50 years of age on long-term antiretroviral therapy and HIV-negative controls, frequency matched by sex and age in Bangkok, Thailand. Nutritional status was assessed by the Mini Nutrition Assessment (MNA) tool. Abnormal nutritional status was defined as MNA score <24 (malnutrition and at risk of malnutrition). Body composition was measured by bioelectrical impedance analysis using Body Composition Analyzer. Demographic and disease-related factors were assessed for their association with abnormal nutrition status using multivariable logistic regression. There were 349 PLHIV and 103 HIV-uninfected controls, with median age 55 years. The majority were male (63%) with median body mass index (BMI) of 23.4 kg/m. PLHIV had lower BMI [median, 23.1 (IQR, 20.8-25.2) vs. 25.3 (22.3-28.7) kg/m,  < .001], lower fat percent [22.8% vs. 26.3%,  < .001] and lower fat mass [14.2 vs. 16.9 kg,  < .001] and higher abnormal nutritional status (18.05% vs. 6.8%,  = .005) than controls. In the multivariate model, older age (adjusted odds ratio [aOR], 1.06, 95% confident interval [CI]: 1.01-1.12,  = .03), positive HIV status (aOR, 2.67, 95% CI: 1.07-6.65,  = .036), diabetes mellitus (aOR, 2.21, 95% CI: 1.003-4.87,  = .049), lower fat mass (aOR, 0.70, 95%CI: 0.57-0.86,  < .001), and lower BMI (aOR, 0.63, 95% CI: 0.51-0.78,  < .001) were independently associated with abnormal nutritional status. PLHIV had higher risks for abnormal nutritional status compared with HIV-uninfected individuals. Regular screening and monitoring of nutritional status among PLHIV may promote better health outcomes.
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http://dx.doi.org/10.1089/AID.2019.0285DOI Listing
July 2020

Short Communication: Carotid Intima-Media Thickness Is Not Associated with Neurocognitive Impairment Among People Older than 50 Years With and Without HIV Infection from Thailand.

AIDS Res Hum Retroviruses 2019 Nov/Dec;35(11-12):1170-1173

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross - AIDS Research Centre, Bangkok, Thailand.

Neurocognitive impairment (NCI) contributes to poor quality of life among HIV-positive individuals. Cardiovascular risk factors, including the predictor of subclinical atherosclerosis, carotid intima-media thickness (cIMT), are reported to be associated with NCI. Data on NCI and its association with cIMT among HIV positive are limited, especially in Asian populations. We aimed to determine the prevalence of NCI and its association with cIMT among HIV-positive and HIV-negative aging Thai individuals. Cognitive performance was evaluated by the Thai version of Montreal Cognitive Assessment (MoCA) with a cutoff of <25/30 for diagnosis of NCI. Depression was evaluated by PHQ-9 Patient Depression Questionnaire, with scores ≥5 indicating depression. cIMT measurement was performed by experienced neurologists, and abnormal cIMT was defined as cIMT ≥0.9 mm or presence of carotid plaques. Among 340 well suppressed and aging HIV-positive and 102 HIV-negative matched participants, the median age (interquartile range) was 55 (52-59) years and 61.5% were males. For HIV positive group, the median duration on antiretroviral therapy was 18.3 years with median CD4 of 615.5 cells/mm, and 97.4% had current plasma HIV RNA <50 copies/mL. The most common antiretroviral agents used were tenofovir disoproxil fumarate (76.8%), lamivudine (70.3%), efavirenz (26.7%), and emtricitabine (23.8%). HIV-positive and HIV-negative participants performed comparably between each domain and had comparable prevalence of NCI (59.4% vs. 61.7%,  = .69). However, the HIV-positive group had a high prevalence of depression (24.71% vs. 13.73%,  = .019). HIV-positive status [adjusted odd ratio (aOR) 0.91; 95% confidence interval (CI) 0.57-1.47,  = .71] and cIMT (aOR 1.17; 95% CI 0.77-1.79,  = .47) were not significantly associated with NCI. Given the high prevalence of NCI and depression among aging HIV-positive individuals, routine screening for NCI and depression should be integrated into the HIV care services.
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http://dx.doi.org/10.1089/AID.2019.0139DOI Listing
September 2020

Trajectory Analysis of Cognitive Outcomes in Children With Perinatal HIV.

Pediatr Infect Dis J 2019 10;38(10):1038-1044

Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis, Missouri.

Background: Children with perinatal HIV (pHIV) may display distinct long-term cognitive phenotypes. We used group-based trajectory modeling to identify clusters of children with pHIV after similar developmental trajectories and predictors of belonging to select cognitive trajectory groups.

Methods: Participants included children, 4-17 years of age, with pHIV in Thailand and Cambodia. Cognitive measures included translated versions of Intelligence Quotient tests, Color Trails Tests and Beery-Buktenica Developmental Test of Visual-Motor Integration conducted semiannually over 3-6 years. The best fit of trajectory groups was determined using maximum likelihood estimation. Multivariate logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group.

Results: Group-based trajectory analyses revealed a 3-cluster classification for each cognitive test, labeled as high, medium and low scoring groups. Most trajectory group scores remained stable across age. Verbal IQ declined in all 3 trajectory groups and the high scoring group for Children's Color Trails Test 1 and 2 showed an increase in scores across age. Children in the lowest scoring trajectory group were more likely to present at an older age and report lower household income.

Conclusions: Group-based trajectory modeling succinctly classifies cohort heterogeneity in cognitive outcomes in pHIV. Most trajectories remained stable across age suggesting that cognitive potential is likely determined at an early age with the exception of a small subgroup of children who displayed developmental gains in select cognitive domains and may represent those with better cognitive reserve. Poverty and longer duration of untreated HIV may predispose children with pHIV to suboptimal cognitive development.
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http://dx.doi.org/10.1097/INF.0000000000002427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776249PMC
October 2019

Screening tools for targeted comprehensive geriatric assessment in HIV-infected patients 50 years and older.

Int J STD AIDS 2019 09 20;30(10):1009-1017. Epub 2019 Aug 20.

1 HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

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http://dx.doi.org/10.1177/0956462419841478DOI Listing
September 2019

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

AIDS Res Ther 2019 04 5;16(1). Epub 2019 Apr 5.

HIV-NAT, Thai Red Cross AIDS Research Centre, 104 Ratchadamri Road, Pathumwan, Bangkok, 10330, Thailand.

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.
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http://dx.doi.org/10.1186/s12981-019-0222-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451290PMC
April 2019

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.

AIDS Res Ther 2018 09 27;15(1):13. Epub 2018 Sep 27.

HIV-NAT, The Thai Red Cross AIDS Research Center, 104 Ratchadamri Rd., Pathumwan, Bangkok, 10330, Thailand.

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/mm (HR: 3.62, 95% CI 2.36-5.55), p < 0.001) vs. < 200 cells/mm 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.
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http://dx.doi.org/10.1186/s12981-018-0200-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158807PMC
September 2018

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

AIDS Care 2018 11 15;30(11):1351-1355. Epub 2018 Mar 15.

a The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Bangkok , Thailand.

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.
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http://dx.doi.org/10.1080/09540121.2018.1450479DOI Listing
November 2018

Cognition, Emotional Health, and Immunological Markers in Children With Long-Term Nonprogressive HIV.

J Acquir Immune Defic Syndr 2018 04;77(4):417-426

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Background: HIV-infected children with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown.

Methods: Eighty-eight LTNPs, 53 Progressors, and 323 healthy controls completed annual assessments of cognitive and emotional health as part of a prospective study. The 2 HIV-infected groups and the healthy controls were matched on age and sex distribution at enrollment. Plasma HIV RNA, T-cell counts/percentages, activated monocytes, perivascular monocytes, and markers of macrophage activation (sCD163 and sCD14) were compared by progression subtype. Cognitive and emotional outcomes were compared using cross-sectional linear regression analysis and longitudinal sensitivity models.

Results: LTNPs exhibited the same cognitive phenotype and emotional dysregulation as Progressors, with worse outcomes in both groups compared with controls. In addition, cognitive and emotional symptoms were evident before children reached the minimum age for LTNP designation (8 years). Baseline plasma HIV RNA, sCD163, activated monocytes, and perivascular monocytes were lower in LTNPs versus Progressors, with no difference in T-cell counts/percentages or sCD14 levels. Most LTNPs converted to a progressive disease subtype during the study, with similar cognitive and emotion profiles between these subgroups.

Conclusions: Pediatric LTNPs experience cognitive and emotional difficulties that mirror symptoms of progressive disease. The abnormalities are present at young ages and persist independent of plasma T-cell counts. The findings highlight the neurodevelopmental risk of pediatric HIV, even in those with early innate disease control.
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http://dx.doi.org/10.1097/QAI.0000000000001619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825279PMC
April 2018

Low-level genital HIV shedding in Thai HIV-infected women with suppressed plasma viral load after menopause: a longitudinal study.

J Virus Erad 2017 Oct 1;3(4):204-207. Epub 2017 Oct 1.

Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Objectives: First, to evaluate the longitudinal changes of HIV RNA in genital secretions in HIV-positive women with plasma HIV RNA <50 copies/mL before and after the onset of menopause. Second, to assess inflammatory markers and prevalence of comorbidities after the onset of menopause.

Methods: This was a prospective observational study with two time points. HIV RNA in genital secretions (GVL) was measured in 15 HIV-positive menopausal women (second time point). Results were compared to earlier available data for GVL from the same participant before the onset of menopause (first time point).

Results: Median age at the first time point was 42 years, and 52 years at the second time point. Median time since the onset of menopause was 2 years and 33% of women were sexually active. Eighty per cent had at least one comorbidity. The GVL before menopause was >50 copies/mL in 27% of the participants, and in 40% after menopause. The GVL was <1000 copies/mL in all but one measurement. There was no significant difference between the two time points (=0.687). Intermediate vaginal flora or bacterial vaginosis was found in 73% of participants during the second time point.

Conclusions: There was a high prevalence of low-level GVL shedding before and after menopause. This needs further investigation, especially in relation to the vaginal microbiome and the complex interactions between micro-organisms. HIV-infected women in menopause do not seem to present a major public health risk for HIV transmission. Nevertheless, safe sex should be discussed with all, regardless of age. The high prevalence of non-communicable diseases after menopause requires special attention and comprehensive care.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632546PMC
October 2017

Implementation of an online HIV prevention and treatment cascade in Thai men who have sex with men and transgender women using Adam's Love Electronic Health Record system.

J Virus Erad 2017 Jan 1;3(1):15-23. Epub 2017 Jan 1.

Thai Red Cross AIDS Research Centre, Bangkok, Thailand; SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Objectives: Electronic health record (EHR) systems have been infrequently used to support HIV service delivery models to optimise HIV prevention and treatment cascades. We have studied the implementation, uptake and use of an EHR among Thai men who have sex with men (MSM) and transgender (TG) women.

Methods: Participants, e-counselled via the Adam's Love ( www.adamslove.org) support platforms, after having completed risk behaviour questionnaires and being assessed for their HIV risk by online counsellors, were enrolled based on their preference into one of three EHR-supported arms: (1) private clinic-based HIV testing and counselling (HTC); (2) online pretest counselling and private clinic-based HIV testing (hybrid); and (3) online supervised HIV self-testing and counselling (eHTC).

Results: Between December 2015 and May 2016, of a total of 489 MSM and TG women were introduced to the study, 186 (38%) enrolled into the study, with 89, 72 and 25 participants joining the HTC, hybrid and eHTC arms, respectively. Seeking sex online was reported by 83.9%. HIV prevalence was highest (16%) in the eHTC arm, and participants in this arm were more likely to be younger (median age 25 29 27 years; =0.01), bisexual (16% 9.7% 5.6%; =0.005), with an unknown history of HIV or first-time HIV testers (48% 25% 19.1%; =0.01) or had tested >1 year ago (15.8% 4.8% 3.4%, =0.04), compared with those in the hybrid and HTC arms. Around half (48.3%) of them revisited the EHR at least once to access laboratory results, read post-test summaries and make an appointment for another HIV test. The participants in the eHTC arm had reduced odds of revisiting the EHR twice or more as compared with participants in the HTC [odds ratio (OR) 0.14, 95% confidence interval (CI) 0.03-0.67, =0.01] and hybrid arms (OR 0.10, 95% CI 0.02-0.44, =0.003). Overall the EHR satisfaction was high at 4.4 (SD 0.68) on a Likert scale of 5.

Conclusions: Young and high-risk MSM and some TG women engaged successfully with the Adam's Love EHR system, showing its potential to support innovative service delivery models and target hard-to-reach and vulnerable populations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337417PMC
January 2017

Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial.

Lancet HIV 2016 08 24;3(8):e343-e350. Epub 2016 May 24.

HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand; Department of Medicine, Faculty of Medicine, Chulalongkorn University, Pathum Wan, Bangkok, Thailand. Electronic address:

Background: Thai patients with HIV have higher exposure to HIV protease inhibitors than do white people and dose reduction might be possible. We compared the efficacy of low-dose with standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai patients with HIV.

Methods: In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years or older who were receiving ritonavir-boosted protease-inhibitor-based antiretroviral therapy (ART) with HIV plasma viral loads of less than 50 copies per mL, an alanine aminotransferase concentration of less than 200 IU/L, and a creatinine clearance of at least 60 mL/min from 14 hospitals in Thailand. We excluded patients who had active AIDS-defining disease or opportunistic infections, had a history of an HIV viral load of 1000 copies per mL or more after 24 weeks of any ritonavir-boosted protease-inhibitor-based ART, used concomitant medications that could interact with the study drugs, were pregnant or lactating, had illnesses that might change the effect of the study drugs, or had a history of sensitivity to the study drugs. A biostatistician at the study coordinating centre randomly allocated patients (1:1) to switch the protease inhibitor for oral atazanavir 200 mg and ritonavir 100 mg or for atazanavir 300 mg and ritonavir 100 mg once daily, both with two nucleoside or nucleotide reverse transcriptase inhibitors at recommended doses. Randomisation was done with a minimisation schedule, stratified by recruiting centre, use of tenofovir, and use of indinavir as a component of the preswitch regimen. The primary endpoint was the proportion of patients with viral loads of less than 200 copies per mL at week 48, and we followed up patients every 12 weeks. Treatments were open label, the non-inferiority margin was -10%, and all patients who received at least one dose of study medication were analysed. This trial is registered with ClinicalTrials.gov, number NCT01159223.

Findings: Between July 6, 2011, and Dec 23, 2013, we randomly assigned 559 patients: 279 to receive atazanavir 200 mg and ritonavir 100 mg (low dose) and 280 to atazanavir 300 mg and ritonavir 100 mg (standard dose). At week 48, 265 (97·1%) of 273 in the low-dose group and 267 (96·4%) of 277 in the standard-dose group had viral loads of less than 200 copies per mL (difference 0·68; 95% CI -2·29 to 3·65). Seven (3%) of 273 in the low-dose group and 21 (8%) of 277 in the standard-dose group discontinued their assigned treatment (p=0·01). 46 (17%) of 273 participants in the low-dose group and 97 (35%) of 277 in the standard-dose group had total bilirubin grade 3 or higher toxicity (≥3·12 mg/dL; p<0·0001).

Interpretation: A switch to low-dose atazanavir should be recommended for Thai patients with well controlled HIV viraemia while on regimens based on boosted protease inhibitors.

Funding: The National Health Security Office and Kirby Institute for Infection and Immunity in Society.
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http://dx.doi.org/10.1016/S2352-3018(16)30010-8DOI Listing
August 2016

Soluble CD163 and monocyte populations in response to antiretroviral therapy and in relationship with neuropsychological testing among HIV-infected children.

J Virus Erad 2015;1(3):196-202. Epub 2015 Jun 30.

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand; Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Monocytes play a central role in HIV neuropathogenesis, but there are limited data on monocyte subsets and markers of monocyte activation in perinatally HIV-infected children.

Objective: To determine the relationship between monocyte subsets, the sCD163 monocyte activation marker, and neuropsychological performance among perinatally HIV-infected children initiating antiretroviral therapy (ART).

Methods: ART-naïve children from the PREDICT study were categorised into two groups: those on ART for ≥24 weeks (ART group, =201) and those untreated (no ART group, =79). This analysis used data from the baseline and week 144 including sCD163 and frequencies of activated monocytes (CD14+/CD16+/HLA-DR+), perivascular monocytes (CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+), and neuropsychological testing scores: Verbal and Performance Intelligence Quotient (VIQ and PIQ), Beery Visuomotor Integration (VMI) and Children's Color Trails 2 (CT2).

Results: Baseline demographic and HIV disease parameters were similar between groups. The median age was 6 years, CD4 was 20% (620 cells/mm), and HIV RNA was 4.8 log. By week 144, the ART the no ART group had significantly higher CD4 (938 552 cells/mm) and lower HIV RNA (1.6 4.38 log copies/mL, <0.05). sCD163 declined in the ART no ART group (median changes -2533 -159 ng/mL, <0.0001). Frequencies of all monocyte subsets declined in the treated but not the untreated group ( <0.05). Higher CD14+/CD16+/HLA-DR+ percentage was associated with higher VIQ, Beery VMI and CT2 scores. Higher percentages of CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+ were associated with higher CT2 and VIQ, respectively.

Conclusion: ART significantly reduced sCD163 levels and frequencies of activated and perivascular monocytes. Higher frequencies of these cells correlated with better neuropsychological performance suggesting a protective role of monocyte-macrophage immune activation in perinatal HIV infection in terms of neuropsychological function.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729380PMC
June 2015

Comparison of adherence monitoring tools and correlation to virologic failure in a pediatric HIV clinical trial.

AIDS Patient Care STDS 2014 Jun;28(6):296-302

1 HIV-NAT, Thai Red Cross AIDS Research Center , Bangkok, Thailand .

There is no consensus on a gold standard for monitoring adherence to antiretroviral therapy (ART). We compared different adherence monitoring tools in predicting virologic failure as part of a clinical trial. HIV-infected Thai and Cambodian children aged 1-12 years (N=207) were randomized to immediate-ART or deferred-ART until CD4% <15%. Virologic failure (VF) was defined as HIV-RNA >1000 copies/mL after ≥6 months of ART. Adherence monitoring tools were: (1) announced pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and (3) child self-report (self-reporting from children or caregivers to direct questioning by investigators during the clinic visit) of any missed doses in the last 3 days and in the period since the last visit. The Kappa statistic was used to describe agreement between each tool. The median age at ART initiation was 7 years with median CD4% 17% and HIV-RNA 5.0 log(10)copies/mL and 92% received zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by announced pill count before VF in VF children was 92% compared to 98% in children without VF (p=0.03). Kappa statistics indicated slight to fair agreement between tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and caregiver education, significant predictors of VF were poor adherence by announced pill count (OR 4.56; 95%CI 1.78-11.69), reporting any barrier to adherence in the PACTG adherence questionnaire (OR 7.08; 95%CI 2.42-20.73), and reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR 8.64; 95%CI 1.96-38.04). In conclusion, we recommend the child self-report of any missed doses since last visit for use in HIV research and in routine care settings, because it is easy and quick to administer and a strong association with development of VF.
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http://dx.doi.org/10.1089/apc.2013.0276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046210PMC
June 2014

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.

J Gastroenterol Hepatol 2014 Sep;29(9):1706-14

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Center, Bangkok, Thailand; Division of Allergy and Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.1111/jgh.12613DOI Listing
September 2014

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

AIDS Res Ther 2014 Jan 22;11(1). Epub 2014 Jan 22.

HIV-NAT, The Thai Red Cross AIDS Research Centre, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand.

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.
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http://dx.doi.org/10.1186/1742-6405-11-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900937PMC
January 2014

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

Asian Pac J Allergy Immunol 2013 Dec;31(4):307-13

Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.12932/AP0306.31.4.2013DOI Listing
December 2013

Decline in serum 25 hydroxyvitamin D levels in HIV-HBV-coinfected patients after long-term antiretroviral therapy.

Antivir Ther 2014 23;19(1):41-9. Epub 2013 Aug 23.

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: Vitamin D insufficiency plays an important role in the development of fibrosis in chronic liver disease.

Methods: This was a cross-sectional study from Thailand. Liver fibrosis was assessed by transient elastography. Serum 25 hydroxyvitamin D (25[OH]D)<30 ng/ml was defined as hypovitaminosis D. 25(OH)D was assessed prior to and following tenofovir disoproxil fumarate (TDF). Factors related to 25(OH)D levels were determined by logistic regression analysis.

Results: A total of 158 HIV-HBV-coinfected patients (32% female, median age 43 years) were included. Overall, liver disease was mild with 13.4% having a fibrosis score (FS) of 7.1-14 kPa and 2% with a FS>14 kPa. Median (IQR) duration on TDF was 5 years (4-7). The median estimated glomerular filtration rate was 96.9 ml/min/1.73 m(2). The median (IQR) serum 25(OH)D levels prior to and following TDF were 24.8 ng/ml (21.3-30.6) and 22.8 ng/ml (18.0-27.7), respectively; P≤0.001). The proportion of patients with hypovitaminosis D significantly increased from 72.2% (95% CI 64.7, 78.6) prior to TDF to 84.2% (95% CI 77.7, 89.0) after taking TDF (P=0.01). Factors associated with hypovitaminosis D by multivariate analysis were female sex (adjusted OR 3.8, 95% CI 1.1, 13.7; P=0.038) and duration of antiretroviral therapy (ART)>5 years (OR 3.3, 95% CI 1.2, 8.8; P=0.017). Vitamin D levels were not associated with significant liver fibrosis.

Conclusions: Although our HIV-HBV-coinfected patients live in the tropics, there was a high prevalence of hypovitaminosis D, especially in female patients and those receiving prolonged ART. Since HIV-HBV-coinfection requires long-term use of the HBV-active drug, TDF, which can also contribute to bone loss, routine vitamin D assessment and supplementation as necessary should be considered.
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http://dx.doi.org/10.3851/IMP2673DOI Listing
November 2014

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

Clin Infect Dis 2013 Jul 19;57(1):147-55. Epub 2013 Mar 19.

TREAT Asia, amfAR/The Foundation for AIDS Research, Klongtoey, Bangkok 10110, Thailand.

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.
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http://dx.doi.org/10.1093/cid/cit173DOI Listing
July 2013

Cognitive function and neurodevelopmental outcomes in HIV-infected Children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study.

Pediatr Infect Dis J 2013 May;32(5):501-8

HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes.

Methods: Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1-12 years with CD4 counts between 15% and 24% and no AIDS-defining illness were randomized to initiate ART at enrollment ("early," n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed ("deferred," n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319).

Results: At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist.

Conclusions: In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%-24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.
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http://dx.doi.org/10.1097/INF.0b013e31827fb19dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664246PMC
May 2013

Prevalence of anemia and underlying iron status in naive antiretroviral therapy HIV-infected children with moderate immune suppression.

AIDS Res Hum Retroviruses 2012 Dec 25;28(12):1679-86. Epub 2012 Jul 25.

Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Anemia is common in HIV-infected children and iron deficiency is thought to be a common cause. This study investigates the prevalence of anemia, thalassemia, and underlying iron status in Thai and Cambodian children without advanced HIV disease to determine the necessity of routine iron supplementation. Antiretroviral (ARV)-naive HIV-infected Asian children aged 1-12 years, with CD4 15-24%, CDC A or B, and hemoglobin (Hb) ≥7.5 g/dl were eligible for the study. Iron studies, serum ferritin, Hb typing, and C-reactive protein were assessed. Anemia was defined as Hb <11.0 g/dl in children <5 years of age or <11.5 g/dl in children 5-12 years. We enrolled 299 children; 57.9% were female and the mean (SD) age was 6.3 (2.9) years. The mean (SD) CD4% and HIV-RNA were 20% (4.6) and 4.6 (0.6) log(10) copies/ml, respectively. The mean (SD) Hb and serum ferritin were 11.2 (1.1) g/dl and 78.3 (76.4) μg/liter, respectively. The overall iron deficiency anemia (IDA) prevalence was 2.7%. One hundred and forty-eight (50%) children had anemia, mostly of a mild degree. Of these, 69 (46.6%) had the thalassemia trait, 62 (41.8%) had anemia of chronic disease (ACD), 9 (6.1%) had thalassemia diseases, 3 (2.0%) had iron deficiency anemia, and 5 (3.4%) had IDA and the thalassemia trait. The thalassemia trait was not associated with increased serum ferritin levels. Mild anemia is common in ARV-naïve Thai and Cambodian children without advanced HIV. However, IDA prevalence is low; with the majority of cases caused by ACD. A routine prescription of iron supplement in anemic HIV-infected children without laboratory confirmation of IDA should be discouraged, especially in regions with a high prevalence of thalassemia and low prevalence of IDA.
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http://dx.doi.org/10.1089/AID.2011.0373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505043PMC
December 2012

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

Microbiol Immunol 2012 Feb;56(2):117-22

Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.1111/j.1348-0421.2011.00413.xDOI Listing
February 2012

The immunogenicity and safety of pneumococcal conjugate vaccine in human immunodeficiency virus-infected Thai children.

Vaccine 2011 Aug 3;29(35):5886-91. Epub 2011 Jul 3.

Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: HIV-infected children have high risk of invasive pneumococcal disease (IPD) despite receiving highly active antiretroviral therapy (HAART). This study aimed to determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed uninfected children.

Methods: A prospective study was conducted among children 2 months to 9 years. The number of PCV-7 doses depended upon age and HIV status; 2-6 months of age: 3 doses; 7-23 months of age: 2 doses; HIV-infected child ≥24 months: 2 doses and HIV-exposed child ≥24 months: 1 dose. Serotype-specific pneumococcal IgG antibody concentrations were measured at baseline and 28 days after complete vaccination. The primary end point was the proportion of children who achieved serotype-specific IgG antibody concentration at a cut off level ≥0.35 μg/mL. Secondary end points were a 4-fold increase in serotype-specific IgG antibody, rates of adverse events and predictors for seroconversion among HIV-infected children.

Results: Fifty-nine HIV-infected and 30 HIV-exposed children were enrolled. The median (IQR) age was 97 (67-111) and 61 months (51-73), respectively (p<0.001). Among HIV-infected children, current and nadir CD4 counts were 1,079 cell/mm(3) and 461 cell/mm(3), respectively. The proportion of children who achieved pneumococcal IgG ≥0.35 μg/mL was in the range of 85-98% in HIV-infected and 83-100% in HIV-exposed children depending on serotype. The lowest response was to serotype 6B in both groups. The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed groups, except for serotype 9V (p=0.027). HIV-infected children who had a history of AIDS had a lower antibody response to serotype 23F (p=0.025). Seven (12%) HIV-infected children had a grade 3 local reaction.

Conclusion: PCV-7 is highly immunogenic and safe among HIV-infected children treated with HAART. The use of the pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent IPD.
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http://dx.doi.org/10.1016/j.vaccine.2011.06.072DOI Listing
August 2011

Characteristics of lymphocyte subsets in HIV-infected, long-term nonprogressor, and healthy Asian children through 12 years of age.

J Allergy Clin Immunol 2010 Dec;126(6):1294-301.e10

HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Background: There are limited data on the immune profiles of HIV-positive children compared with healthy controls, and no such data for Asian children.

Objectives: To immunophenotype HIV-positive Asian children, including long-term nonprogressors (LTNPs), compared with age-matched healthy controls.

Methods: We used flow cytometry to analyze 13 lymphocyte and monocyte subsets from 222 untreated, HIV-positive children with 15% to 24% CD4(+) T cells and no AIDS-related illnesses and 142 healthy children (controls). Data were compared among age categories. Profiles from LTNPs (n = 50), defined as children ≥8 years old with CD4(+) T-cell counts ≥350 cells/mm(3), were compared with data from age-matched non-LTNPs (n = 17) and controls (n = 53).

Results: Compared with controls, HIV-positive children had lower values (cell count per mm(3) and percent distribution) for T(H) cells and higher values for cytotoxic T cells, with reductions in populations of naive T(H) and cytotoxic T cells, B cells, and natural killer (NK) cells. HIV-positive children had high values for activated T(H) and cytotoxic T cells. Compared with non-LTNPs, LTNPs had higher values of T(H) and cytotoxic T cells, naive and memory T-cell subsets, and B and NK cells. Surprisingly, counts of activated T(H) and cytotoxic T cells were also higher among LTNPs. LNTPs were more frequently male.

Conclusion: Untreated, HIV-infected Asian children have immune profiles that differ from those of controls, characterized by low values for T(H) cells, naive T cells, B cells, and NK cells but high values for cytotoxic, activated T(H), and cytotoxic T cells. The higher values for activated T cells observed in LTNPs require confirmation in longitudinal studies.
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http://dx.doi.org/10.1016/j.jaci.2010.09.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004741PMC
December 2010