Publications by authors named "Kiat Ruxrungtham"

255 Publications

COVID-19 and HIV infection co-pandemics and their impact: a review of the literature.

AIDS Res Ther 2021 05 5;18(1):28. Epub 2021 May 5.

Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.
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http://dx.doi.org/10.1186/s12981-021-00335-1DOI Listing
May 2021

DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice.

PLoS One 2021 22;16(3):e0248007. Epub 2021 Mar 22.

Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center, Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

More than 65 million people have been confirmed infection with SARS-CoV-2 and more than 1 million have died from COVID-19 and this pandemic remains critical worldwide. Effective vaccines are one of the most important strategies to limit the pandemic. Here, we report a construction strategy of DNA vaccine candidates expressing full length wild type SARS-CoV-2 spike (S) protein, S1 or S2 region and their immunogenicity in mice. All DNA vaccine constructs of pCMVkan-S, -S1 and -S2 induced high levels of specific binding IgG that showed a balance of IgG1/IgG2a response. However, only the sera from mice vaccinated with pCMKkan-S or -S1 DNA vaccines could inhibit viral RBD and ACE2 interaction. The highest neutralizing antibody (NAb) titer was found in pCMVkan-S group, followed by -S1, while -S2 showed the lowest PRNT50 titers. The geometric mean titers (GMTs) were 2,551, 1,005 and 291 for pCMVkan-S, -S1 and -S2, respectively. pCMVkan-S construct vaccine also induced the highest magnitude and breadth of T cells response. Analysis of IFN-γ positive cells after stimulation with SARS-CoV-2 spike peptide pools were 2,991, 1,376 and 1,885 SFC/106 splenocytes for pCMVkan-S, -S1 and -S2, respectively. Our findings highlighted that full-length S antigen is more potent than the truncated spike (S1 or S2) in inducing of neutralizing antibody and robust T cell responses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248007PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984610PMC
April 2021

Novel Criteria for Diagnosing Acute and Early HIV Infection in a Multi-National Study of Early Antiretroviral Therapy Initiation.

Clin Infect Dis 2020 Dec 31. Epub 2020 Dec 31.

Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.

Background: Antiretroviral therapy (ART) initiation during acute and early HIV infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of new AEHI diagnostic criteria from a multi-national prospective study of ART initiation during AEHI.

Methods: ACTG 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any one of six criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Combo Ag/Ab CMIA or GS HIV COMBO Ag/Ab EIA. HIV infection and Fiebig stage were subsequently confirmed by centralized testing.

Results: From 2017-2019, 195 participants were enrolled with median age 27 (interquartile range 23-39) years. Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, four (2.0%) participants were retrospectively found to have chronic infection, and three (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results.

Conclusions: Novel AEHI criteria incorporating ARCHITECT S/CO into diagnostic algorithms facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These new criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice.
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http://dx.doi.org/10.1093/cid/ciaa1893DOI Listing
December 2020

Incident Liver Cirrhosis, Associated Factors, and Cardiovascular Disease Risks Among People Living With HIV: A Longitudinal Study.

J Acquir Immune Defic Syndr 2021 Apr;86(4):463-472

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

Objectives: We investigated the incidence and associated factors of liver cirrhosis and cardiovascular disease risks among people living with HIV (PLHIV) in a Thai cohort.

Design: A prospective cohort analysis.

Methods: Participants with at least one reliable transient elastography measurement during follow-up, who had pretreatment alanine transaminase, AST, and platelet count at HIV treatment initiation were included. Liver cirrhosis was defined as AST to Platelet Ratio Index >1.5 or fibrosis-4 (FIB-4) >3.25 or liver stiffness by transient elastography >12.5 kPa and confirmed by imaging or liver biopsy. Competing-risk regression was used to identify factors associated with liver cirrhosis. Time-updated 10-year atherosclerotic CVD (ASCVD) risks were compared between PLHIV with or without liver cirrhosis.

Results: A total of 1069 participants (33% women, 9% hepatitis C virus, and 16% hepatitis B virus) with the median age and CD4 at cART initiation of 32 years and 240 cells/mm3 were included. During 8232 person-years, 124 (12%) developed liver cirrhosis after a median of 6.9 (2.4-13.7) follow-up years [incidence, 1.5 (95% confidence interval: 1.3 to 1.8) per 100 person-years]. In multivariable analysis, the factors independently associated with liver cirrhosis were time-updated HIV viremia, hepatitis B virus, and hepatitis C virus coinfection, diabetes mellitus, high-density lipoproteins <40 mg/mL, and d4T exposure. The median time-updated 10-year ASCVD risk score was statistically higher among cirrhotic PLHIV vs. noncirrhosis [4.9% (interquartile range, 2.3-9.7) vs. 2.4% (interquartile range, 1.3-4.9), P < 0.001].

Conclusion: PLHIV with metabolic diseases were more likely to develop liver cirrhosis, independent of hepatitis coinfections, and ASCVD risks were higher among cirrhotic individuals.
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http://dx.doi.org/10.1097/QAI.0000000000002585DOI Listing
April 2021

Performance of a simple flow cytometric assay in diagnosing active tuberculosis.

Tuberculosis (Edinb) 2021 01 11;126:102017. Epub 2020 Nov 11.

The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.

A flow cytometric assay measuring Mycobacterium tuberculosis-specific CD4 T-cell responses using co-expression of CD25/CD134 (OX40 assay) was explored as a diagnostic tool for active tuberculosis (TB) in a Thai population with and without HIV infection. Peripheral blood mononuclear cells (PBMC) obtained from 133 participants at TB diagnosis were cryopreserved. Seventy-six participants had a clinical diagnosis of TB which were confirmed by a positive culture. CD4 T-cell responses were measured after stimulation with a pool of overlapping peptides covering RD-1 antigens: CFP-10 + ESAT-6. The performance of the assay was also compared to the Xpert MTB/RIF assay. The overall sensitivity of the OX40 assay was 94.7% (95%CI 87.1-98.5); its specificity was 71.9% (95%CI, 58.5-83). The sensitivity of the OX40 assay among HIV-infected participants was 100% (95%CI, 88.8-100) with a specificity of 92.9% (95%CI, 66.1-99.8). OX40 assay performed particularly well in those with active TB and HIV infection.
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http://dx.doi.org/10.1016/j.tube.2020.102017DOI Listing
January 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

Rapid antiretroviral initiation among Thai youth living with HIV in the National AIDS programme in the era of treatment at any CD4 cell count: a national registry database study.

J Int AIDS Soc 2020 09;23 Suppl 5:e25574

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

Introduction: The process indicators of ending the HIV epidemic include 90% of people living with HIV receiving antiretroviral therapy (ART). The population of youth, however, has less access to healthcare. We assessed ART initiation and attrition outcomes of the HIV continuum from HIV diagnosis to ART initiation in youth living with HIV (YLHIV) and factors associated with ART initiation.

Methods: We studied YLHIV aged 15 to 24 years who were registered on the National AIDS Program (NAP) from January 2008 to May 2019. The study period was divided into 2008 to 2013 (initiated ART by CD4-guided criteria) and 2014 to 2018 (initiate ART at any CD4). Date of registration was used as a surrogate for the diagnosis date and defined as the baseline. The database included ART prescription and laboratory results, and the vital status was linked daily with the National Death Registry. Competing risk methods were used to assess factors associated with accessing ART, with loss to follow-up (LTFU) and death considered as competing events. Logistic regression was used to assess factors associated with rapid ART initiation, defined as initiation ≤1 month after registration.

Results: Overall, 51,607 youth registered on the NAP (42% between 2008 and 2013). Median age was 21 (IQR 20 to 23) years; 64% were male. Overall ART initiation was 80% in the first period and 83% in the second. The ART initiation rate was higher among YLHIV aged 15 to 19 years (86%) than 20 to 24 years (82%) (p < 0.001) in the second period. The proportion of youth starting rapid ART increased significantly from 27% to 52% between the two periods (p < 0.001). Factors associated with ART initiation were age 15 to 19 years (aSHR 1.09, 95% CI 1.06 to 1.11), female (aSHR 1.26, 95% CI 1.23 to 1.29) and registration year 2014 to 2018 (aSHR 1.73, 95% CI 1.69 to 1.76). The cumulative incidence of LTFU/death prior to ART initiation at 12 months was 3.8% (95% CI 3.6% to 4.1%) in the first period and 1.9% (95% CI 1.8% to 2.1%) in the second period.

Conclusions: In the era of universal treatment of all at any CD4 level, 83% of YLHIV registered on the Thai National AIDS Program initiated ART. The majority initiated within one month of registration.
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http://dx.doi.org/10.1002/jia2.25574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459169PMC
September 2020

A randomized, double-blind, placebo-controlled trial on the effect of intranasal corticosteroid as a treatment for moderate to severe obstructive sleep apnea with coexisting chronic rhinitis.

Asian Pac J Allergy Immunol 2020 Aug 23. Epub 2020 Aug 23.

Division of Pulmonary and Critical Care medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Chronic rhinitis is a common co-existing disease with obstructive sleep apnea (OSA). Current evidence on intranasal steroid efficacy as a treatment modality is scarce.

Objective: This study assessed the efficacy of intranasal steroid in moderate to severe OSA with coexisting chronic rhinitis.

Methods: A prospective randomized, double-blind, placebo-controlled trial was conducted in non-2nd to 3rd degree obese, non-severe oropharyngeal obstruction, moderate to severe OSA with coexisting chronic rhinitis (total nasal symptom score (TNSS) ≥ 6, BMI < 30 kg/m2, modified Mallampati < 3). We randomized the patients to receive intranasal steroid (fluticasone furoate, 110 mcg/day) or placebo for one-month duration. The primary end point was the change in apnea hypopnea index (AHI).

Results: A total of 34 patients were randomly assigned to receive intranasal steroid (N = 18) or placebo (N = 16). The adjusted absolute difference mean change of AHI did not show significant difference (11.5 ± 7.9 events/hour [95% CI; -4.9 to 27.8; p = 0.16]). Interestingly, significant reduction in non-supine respiratory disturbance index (RDI) (56.1 ± 21.9 events/hour [95% CI; 18.9 to 93.2; p = 0.01]) was observed in intranasal steroid group. When comparison was made within group, only intranasal steroid group demonstrated significant reduction in AHI, RDI, NREM RDI, TNSS, and Thai Pittsburgh sleep quality index (p = 0.02, 0.02, 0.01, 0.003, and < 0.001; respectively) after receiving the drug.

Conclusions: In moderate to severe OSA patients with coexisting chronic rhinitis, intranasal steroid demonstrated significant reduction in obstructive respiratory events during non-supine sleep. Intranasal steroid may be considered as adjunctive or alternative to OSA treatment.
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http://dx.doi.org/10.12932/AP-070320-0785DOI Listing
August 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

Immunogenicity and safety of the AS04-HPV-16/18 and HPV-6/11/16/18 human papillomavirus vaccines in asymptomatic young women living with HIV aged 15-25 years: A phase IV randomized comparative study.

EClinicalMedicine 2020 Jun 25;23:100353. Epub 2020 May 25.

GSK, Avenue Fleming 20, 1300 Wavre, Belgium.

Background: Women living with HIV (WLWH) are at higher risk of acquisition and progression of human papillomavirus (HPV) infection. Evidence on effect of HPV vaccination in this population is limited.

Methods: This phase IV randomized controlled observer-blind study assessed immunogenicity and safety of two HPV vaccines (AS04-HPV-16/18 vs. 4vHPV) given in WLWH (stage 1) and HIV- females aged 15-25 years. Co-primary endpoints were to demonstrate, in WLWH subjects, non-inferiority (and if demonstrated, superiority) of AS04-HPV-16/18 vs. 4vHPV for HPV-16 and HPV-18 by pseudovirion-based neutralization assay (PBNA) at month 7 and safety. Non-inferiority criteria was lower limit (LL) of the 95% confidence interval (CI) of the GMT ratio AS04-HPV-16/18/4vHPV above 0.5, in the according to protocol population. NCT01031069.

Findings: Among 873 subjects recruited between 26-Oct-2010 and 14-May-2015, 546 were randomized (1:1) and received at least one vaccine dose (total vaccinated cohort, TVC): 257 were WLWH (129 AS04-HPV-16/18; 128 4vHPV) and 289 were subjects without HIV (144 AS04-HPV-16/18; 145 4vHPV). Baseline CD4 cell count in WLWH was at least 350 cells/mm.At month 7, AS04-HPV-16/18 showed immunological superiority to 4vHPV in WLWH. Neutralizing anti-HPV-16 and HPV-18 antibody GMTs were 2·74 (95% CI: 1·83; 4·11) and 7·44 (95% CI: 4·79; 11·54) fold higher in AS04-HPV-16/18 vs. 4vHPV (LL of the GMT ratio >1 in TVC, <0·0001), respectively. Similar results were observed by ELISA up to month 24.Solicited local and general symptoms were in line with product labels. The number of reported serious adverse events (SAEs) was balanced throughout the study.

Interpretation: Both vaccines showed an acceptable safety profile in all subjects. Despite the absence of an immunological correlate of protection for HPV, differences in immune responses elicited by the vaccines especially for HPV-18 may translate into longer lasting or more robust protection against cervical cancer with the AS04-HPV-16/18 vaccine in WLWH.
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http://dx.doi.org/10.1016/j.eclinm.2020.100353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329699PMC
June 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

Pharmacokinetics of nucleoside/nucleotide reverse transcriptase inhibitors for the treatment and prevention of HIV infection.

Expert Opin Drug Metab Toxicol 2020 Jul 7;16(7):551-564. Epub 2020 Jun 7.

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

Introduction: Despite dramatic increases in new drugs and regimens, a combination of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) remains the backbone of many regimens to treat HIV.

Area Covered: This article summarizes the pharmacokinetic characteristics of approved NRTIs that are currently in the international treatment and prevention guidelines.

Expert Opinion: Compared to other NRTIs, tenofovir alafenamide fumarate (TAF) is more advantageous in terms of potency and safety. It is therefore a preferred choice in combination with emtricitabine (FTC) in most HIV treatment guidelines. The efficacy of the two-drug combination of NRTI/Integrase strand-transfer inhibitor, i.e. lamivudine/dolutegravir has been approved as an option for initial therapy. This regimen however has some limitations in patients with HBV coinfection. The two NRTI combinations tenofovir disproxil fumarate (TDF)/FTC and TAF/FTC have also been approved for pre-exposure prophylaxis (PrEP). Interestingly, a promising long-acting nucleoside reverse transcriptase translocation inhibitor, islatravir, formulated for implant was well tolerated and remained effective for up to a year, suggesting its potential as a single agent for PrEP. In the next decade, it remains to be seen whether NRTI-based regimens will remain the backbone of preferred ART regimens, or if the treatment will eventually move toward NRTI-sparing regimens to avoid long-term NRTI-toxicity.
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http://dx.doi.org/10.1080/17425255.2020.1772755DOI Listing
July 2020

Sleep Quality of Hospitalized Patients, Contributing Factors, and Prevalence of Associated Disorders.

Sleep Disord 2020 20;2020:8518396. Epub 2020 Jan 20.

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

Background: Data in the literature has shown poor sleep quality to be frequently observed in hospitalized patients and known to be associated with poor treatment outcome. Many factors may impact poor sleep quality, and there is currently limited available data. We aim to determine the prevalence of poor sleep quality and associated factors in patients admitted to internal medicine wards as well as the change of sleep quality over time after admission.

Methods: An analytic observational study was conducted at the internal medicine wards at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients were personally interviewed to evaluate the history of sleep quality at home, sleep quality after the first and the third days of admission, and potential associated factors. The Pittsburgh Sleep Quality Index and screening questionnaires for the common diseases associated with poor sleep quality were also utilized. The logistic regression analysis was used to determine the independent factors which led to poor sleep quality.

Results: Data were collected from 96 patients during the period of June 2015 to February 2016. The mean age of the patients was 50.8 ± 16.7 years, and 51% were male. Infectious disease was the most common principal diagnosis accounted for 29.2%. The results show high prevalence of poor sleep quality after the first night of admission compared to baseline sleep quality at home (50% vs. 18.8%; < 0.001). After 3 days of admission, the prevalence of poor sleep quality was reduced to the level close to baseline sleep quality at home (28.1% vs. 18.8%; = 0.13). Multivariate analysis demonstrated that light exposure and pain were the main independent factors for poor sleep quality on the first day (odds ratio 6.68; 95% CI 2.25-19.84) and on the third day (odds ratio 3.47; 95% CI 1.24-9.71), respectively.

Conclusions: This is the first study conducted on the sleep quality of hospitalized patients that included the follow-up period during hospital admission. Our study demonstrated high prevalence of poor sleep quality in hospitalized patients on the first day. Interestingly, the sleep quality was partly improved during hospitalization. Light exposure and pain were demonstrated to be the factors associated with poor sleep quality.
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http://dx.doi.org/10.1155/2020/8518396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157800PMC
January 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

Impact of early antiretroviral treatment on sexual behaviour: a randomised comparison.

AIDS 2019 12;33(15):2337-2350

Institute for Global Health, University College London, London, UK.

Background: Antiretroviral treatment (ART) reduces HIV infectiousness but the effect of early ART on sexual behaviour is unclear.

Methods: We assessed, within the START randomized trial that enrolled HIV-positive adults with CD4 cell count greater than 500 cells/μl, the effect of early (immediate) versus deferred ART on: condomless sex with HIV-serodifferent partners (CLS-D); all condomless sex (CLS); HIV transmission-risk sex (CLS-D-HIV risk, defined as CLS-D and: not on ART or started ART <6 months ago or viral load greater than 200 copies/ml or no viral load in past 6 months), during 2-year follow-up. Month-12 CLS-D (2010-2014) was the primary outcome.

Results: Among 2562 MSM, there was no difference between immediate and deferred arms in CLS-D at month 12 [12.6 versus 13.1%; difference (95% CI): -0.4% (-3.1 to 2.2%), P = 0.75] or month 24, or in CLS. Among 2010 heterosexual men and women, CLS-D at month 12 tended to be higher in the immediate versus deferred arm [10.8 versus 8.3%; difference:2.5% (-0.1 to 5.2%), P = 0.062]; the difference was greater at month 24 [9.3 versus 5.6%; difference: 3.7% (1.0 to 6.4%), P = 0.007], at which time CLS was higher in the immediate arm (20.7 versus 15.7%, P = 0.013). CLS-D-HIV risk at month 12 was substantially lower in the immediate versus deferred arm for MSM [0.2 versus 11%; difference: -10.7% (-12.5 to -8.9%), P < 0.001] and heterosexuals [0.6% versus 7.7%; difference: -7.0% (-8.8 to -5.3%), P < 0.001], because of viral suppression on ART.

Conclusion: A strategy of early ART had no effect on condomless sex with HIV-serodifferent partners among MSM, but resulted in modestly higher prevalence among heterosexuals. However, among MSM and heterosexuals, early ART resulted in a substantial reduction in HIV-transmission-risk sex, to a very low absolute level.
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http://dx.doi.org/10.1097/QAD.0000000000002359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882545PMC
December 2019

Treatment outcomes and factors associated with mortality among individuals with both TB and HIV in the antiretroviral era in Thailand.

J Virus Erad 2019 Nov 4;5(4):225-230. Epub 2019 Nov 4.

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

Objective: This study aimed to compare treatment outcomes and factors associated with mortality in HIV-1-positive and HIV-1-negative individuals.

Methods: We conducted a cohort study between July 2008 and December 2016. Logistic regression was used to determine factors associated with outcomes and death after tuberculosis (TB) treatment.

Results: A total of 996 individuals with TB, 228 (22.9%) with HIV-1 co-infection and 770 (77.1%) who were HIV-1 negative were reviewed. The overall treatment success rate was 74.3%. The HIV-1-negative individuals with TB had significantly higher treatment success rates (77.2% 64.5%,  < 0.001). Using logistic regression analysis, age >50 years (adjusted odds ratio [aOR] 3.89, 95% confidence interval [CI] 2.24-6.76;  < 0.001), body weight ≤45 kg (aOR 2.19, 95% CI 1.14-4.19;  = 0.02) and HIV-1-positive status (aOR 3.31, 95% CI 1.84-5.91;  < 0.001) were independently associated with death during TB treatment. Among HIV-1-positive individuals, not undergoing antiretroviral therapy (ART), having diabetes and a CD4 T cell count of <50 cells/mm were significantly associated with death.

Conclusion: Individuals who had both TB and HIV-1 in Thailand had lower TB treatment success and higher mortality rates compared with individuals with TB without HIV-1. Strategies to improve ART uptake and to reduce risk of developing active TB among individuals with advanced HIV-1 infection should be scaled up.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844402PMC
November 2019

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

Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial.

Lancet Respir Med 2019 11 30;7(11):951-963. Epub 2019 Sep 30.

Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Background: Since the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.

Methods: This randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013-14 to 2017-18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov, NCT02287467.

Findings: 313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79-1·97; p=0·33). In subgroup analyses for the primary outcome, the OR in patients with influenza A was 0·94 (0·55-1·59) and was 3·19 (1·21-8·42) for those with influenza B (interaction p=0·023). Through 28 days of follow-up, 47 (30%) of 156 patients in the hIVIG group and in 45 (30%) of 152 patients in the placebo group had the composite safety outcome of death, a serious adverse event, or a grade 3 or 4 adverse event (hazard ratio [HR] 1·06, 95% CI 0·70-1·60; p=0·79). Six (4%) patients in the hIVIG group and five (3%) in the placebo group died, but these deaths were not necessarily related to treatment.

Interpretation: When administered alongside standard care (most commonly oseltamivir), hIVIG was not superior to placebo for adults hospitalised with influenza infection. By contrast with our prespecified subgroup hypothesis that hIVIG would result in more favourable responses in patients with influenza A than B, we found the opposite effect. The clinical benefit of hIVIG for patients with influenza B is supported by antibody affinity analyses, but confirmation is warranted.

Funding: NIAID and NIH. Partial support was provided by the Medical Research Council (MRC_UU_12023/23) and the Danish National Research Foundation.
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http://dx.doi.org/10.1016/S2213-2600(19)30253-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868512PMC
November 2019

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

Clin Infect Dis 2020 05;70(11):2317-2324

Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background: Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding.

Methods: From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study. Eligible participants were randomized to receive oseltamivir 75 mg or placebo twice daily for 5 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at day 3.

Results: Of 716 adults screened for the study, 558 were randomized, and 501 were confirmed to have influenza. Forty-six participants in the pilot study were excluded, and 449 of the 455 participants in the population for the primary analysis had day 3 viral shedding results. Ninety-nine (45.0%) of 220 participants in the oseltamivir arm had virus detected at day 3 compared with 131 (57.2%) of 229 participants in the placebo arm (absolute difference of -12.2% [-21.4%, -3.0%], P =; .010). The median time to alleviation of symptoms was 79.0 hours for the oseltamivir arm and 84.0 hours for the placebo arm (P =; .34) in those with confirmed influenza infection.

Conclusions: Oseltamivir decreased viral shedding in this low-risk population. However, in the population enrolled in this study, it did not significantly decrease the time to resolution of clinical symptoms.

Clinical Trials Registration: NCT01314911.
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http://dx.doi.org/10.1093/cid/ciz634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245154PMC
May 2020

Low CD4 Cell Counts Are Associated with Carotid Plaque and Intima-Media Thickness in Virologically Suppressed HIV-Infected Asians Older Than 50 Years.

AIDS Res Hum Retroviruses 2019 Nov/Dec;35(11-12):1160-1169. Epub 2019 Oct 29.

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

Information about the prevalence, and risk factors for subclinical atherosclerosis in an Asian HIV-infected population is limited. Carotid intima-media thickness (cIMT) is one predictor for the risk of cardiovascular disease (CVDs) and mortality. We evaluated the prevalence and risk factors related to carotid atherosclerosis among well-suppressed HIV-infected adults receiving long-term ART from Thailand. This was a cross-sectional study of HIV-infected adults >50 years of age and free from CVDs from Thailand during 1 March 2016 and 30 May 2017. Ultrasonography of the carotid was performed and read by cIMT experienced neurologists who were blinded from the patient care. Subclinical atherosclerosis was defined by carotid plaque or cIMT of the common carotid artery (CCA) >0.9 mm. Totally 316 HIV-infected adults (61% males) were included. Median age was 54.4 years and 15.8% were diabetic, 40.2% had hypertension, and 12.7% were current smokers. The median duration of ART was 16.3 years and 32% were currently on boosted protease inhibitor. The mean overall cIMT of the common carotid arteries were 0.63 (IQR 0.55-0.72) mm. Men had higher cIMT than women, 0.64 (IQR 0.56-0.76) vs. 0.60 (IQR 0.53-0.70),  = .03. Overall, 3.8% had cIMT >0.9 mm and 24.4% had carotid plaque. From the multivariate logistic regression analysis, age per 1 year increase [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.003-1.12;  = .04] and nadir CD4 < 200 cells/mm (OR 1.8; 95%CI 1.02-3.18,  = .04) were significantly associated with subclinical atherosclerosis. High-sensitivity C-reactive protein was not associated with subclinical atherosclerosis. In this well-suppressed HIV-infected Aging Asian cohort with relatively low prevalence of current smokers, 26.9% of them had subclinical atherosclerosis. Advanced age and low nadir CD4 cell count were significantly associated with subclinical atherosclerosis. Given that approximately a quarter of the patients had carotid plaques, longitudinal studies to evaluate the development of future overt coronary artery disease and stroke are warranted.
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http://dx.doi.org/10.1089/AID.2019.0126DOI Listing
September 2020

Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials.

HIV Res Clin Pract 2019 Jul 8:1-9. Epub 2019 Jul 8.

j Gilead Sciences , Foster City , California , USA.

The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive and ART-experienced Asian participants infected with human immunodeficiency virus (HIV)-1 through 96 or 144 weeks. In Asian population requiring treatment, it is imperative to have data specific to this group, particularly as there is a general concern that Asians with lower body weight have increased risk of tenofovir disoproxil fumarate (TDF)-related renal dysfunction. Studies -104 and 111 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naive participants, comparing E/C/F/TAF versus E/C/F/TDF. Study 109 was a randomized, open-label, 96-week study conducted in virologically suppressed, ART-experienced participants, who switched to E/C/F/TAF from ritonavir/cobicistat-boosted atazanavir ATV+(RTV or COBI) + F/TDF regimens, from non-nucleoside reverse transcriptase inhibitors (NNRTI) + F/TDF regimens, or from E/C/F/TDF. Study 112 was a single arm, open-label, 144-week study conducted in HIV suppressed, ART-experienced participants with mild-moderate renal impairment, who switched to E/C/F/TAF. Asian participants in these studies had sustained efficacy safety and tolerability. In Study 104/111, Asian participants achieved 93% virologic suppression on TAF vs 88% on TDF at week 144. At baseline, there were numerically more Asians with median CD4 counts < 200 cells/uL and VL > 100,000 c/mL. In Study 109, 95% of Asians on TAF vs 86% on TDF maintained virologic suppression at week 96. Lastly, in Study 112, 91% maintained virologic suppression at week 144. There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies.
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http://dx.doi.org/10.1080/15284336.2019.1589232DOI Listing
July 2019

Influence of and polymorphisms on atazanavir/r concentrations in Thai HIV-infected patients.

Pharmacogenomics 2019 05;20(7):517-527

Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.

To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). The concentration-to-dose ratios were compared between different genotype groups of , ,  and in 490 patients. Multiple regression analysis was used to examine the association between genetic and clinical factors and log-transformed concentration-to-dose ratio of ATV and RTV. Higher concentrations of ATV and RTV were significantly associated with 6986 GG and 521 TC or CC. Female patients had significantly higher ATV plasma concentration than male patients. Genetic polymorphisms and gender are factors affecting the variability of ATV and RTV concentrations in the Thai population. Thus, genetic testing is worth considering when atazanavir + low dose ritonavir is prescribed.
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http://dx.doi.org/10.2217/pgs-2018-0196DOI Listing
May 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

Attrition and treatment outcomes among adolescents and youths living with HIV in the Thai National AIDS Program.

J Virus Erad 2019 Jan 1;5(1):33-40. Epub 2019 Jan 1.

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

Background: There are limited data describing the care outcome of youth living with HIV in Asia. We assessed attrition and treatment outcomes among youths with behaviourly acquired HIV (BIY) and adolescents with perinatally acquired HIV (PIY) who initiated antiretroviral treatment (ART) through the National AIDS Program (NAP) in Thailand.

Methods: People living with HIV aged 10-24 years who initiated antiretroviral therapy (ART) from 2008 to 2013 through the Thai NAP and who were followed up until 2014 were included in the analysis. We assessed youths initiating ART: BIY aged 15-19 years (BIY1) and BIY aged 20-24 (BIY2) compared against PIY aged 10-14 years. Attrition rates (mortality and loss to follow-up [LTFU]) were calculated and potential associations were assessed using Cox regression. Logistic regression was used to assess associations with treatment failure.

Results: Of 11,954 individuals, 9909 (83%) were BIY with a median follow-up of 2.1 years and 17% were PIY with 4.2 years of follow-up. The median baseline CD4 cell count in BIY was higher (190 154 cells/mm) compared to PIY. Mortality rates were not significantly different among PIY (2.5 per 100 person years [PY], BIY1 3.1/100 PY and BIY2 2.9/100 PY, =0.46). Compared to PIY with a crude LTFU rate of 2.9/100 PY, LTFU was higher in BIY1 (13.9/100 PY) and BIY2 (9.5/100 PY), <0.001 and <0.001, respectively. At 1 year after initiating ART, 16% experienced virological failure (viral load above 1000 copies/mL). Combined treatment failure and LTFU rates at 1 year after ART were higher among BIY1 (45.0%) and BIY2 (34.4%) compared to PIY (29.9%), <0.001 and 0.001, respectively.

Conclusion: Youth with behaviourally acquired HIV aged 15-19 years had poorer retention rates than older BIY and PIY. Targeted interventions for youth are urgently needed to improve overall treatment outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362904PMC
January 2019

Comparable carotid intima-media thickness among long-term virologically suppressed individuals with HIV and those without HIV in Thailand.

J Virus Erad 2019 Jan 1;5(1):23-27. Epub 2019 Jan 1.

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

Objectives: This study compared the carotid intima-media thickness (cIMT) among well suppressed adult participants living with HIV and adults without HIV, aged >45 years.

Methods: A cross-sectional, age and sex-matched study was conducted at two sites in Thailand: King Chulalongkorn Memorial Hospital (KCMH) and HIV-NAT. All participants had no evidence of coronary artery disease (CAD). Ultrasonography of the carotid artery was measured by one well-trained neurologist who was blinded to the participants' care. The primary endpoint was the difference in cIMT between participants with HIV and controls without HIV. Prevalence and predictive risk of cIMT≥0.9 mm were determined.

Results: Of 90 individuals, 60 were living with HIV. The overall median (IQR) age was 54.1 (52-60) years and 53.3% were male. For the group with HIV, the median duration of ART was 15 years and 33% were on boosted PIs. Compared to controls without HIV, the group with HIV had a higher proportion of hypertriglyceridaemia (48.3% 26.7%, =0.049) but the median overall cIMT of the common carotid arteries (0.665 mm 0.649 mm, =0.277) and serum high-sensitivity C-reactive protein (hs-CRP) (1.59 mg/dL 1.46 mg/dL, =0.325) were not different. Hs-CRP was not correlated with cIMT ≥0.9 mm. However, carotid plaques (=6) were found only among the group with HIV. From the multivariate analysis, only male sex and hypertension were significantly associated with cIMT ≥0.9 mm.

Conclusions: Well-controlled and long-term treated participants living with HIV had comparable cIMT to Thai adults without HIV. Monitoring for progression of cIMT, carotid plaques and cardiovascular disease in this population is warranted to guide continued management.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362911PMC
January 2019

Dengue vaccine: Global development update.

Asian Pac J Allergy Immunol 2020 Sep;38(3):178-185

Chula Vaccine Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

The first licensed dengue vaccine, CYD-TDV (Dengvaxia®), has received regulatory approval in a number of countries. However, this vaccine has some limitations. Its efficacy against DENV2 was consistently lower than other serotypes. Protective efficacy also depended on prior dengue sero-status of the vaccinees. Lower efficacy was observed in children with < 9 years old and dengue-na?ve individuals. More importantly, risk of hospitalization and severe dengue was increased in the youngest vaccine recipients (2-5 years) compared to controls. Thus, the quest of a better vaccine candidate continues. There are two live-attenuated vaccine candidates currently testing in phase III trial including DENVax, developed by US CDC and Inviragen (now licensed to Takeda) and TV003/TV005, constructed by US NIAID. In addition, there are several phase I-II as well as preclinical phase studies evaluating vaccines for safety and immunogenicity, this include other live-attenuated platform/strategy, purified-inactivated viruses formulated with adjuvants, DNA vaccine, subunit vaccine, viral vector and also heterologous prime/boost strategies. The major difficulties of dengue vaccine development are included the lack of the best animal model, various immune status of individual especially in endemic areas and clear cut off of protective immunity. Several research and development efforts are ongoing to find a better effective and accessible dengue vaccine for people needed.
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http://dx.doi.org/10.12932/AP-100518-0309DOI Listing
September 2020

Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy.

J Allergy Clin Immunol 2019 03 5;143(3):1077-1086.e10. Epub 2018 Dec 5.

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. Electronic address:

Background: Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported.

Objective: Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients.

Methods: B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG- and IgG-switched Der p 1-specific B cells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT.

Results: Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23 ± 0.28 to 2.45 ± 0.24 (P = .001) and a decrease in skin prick test reactivity to house dust mite from 7.0 ± 1.3 to 2.7 ± 0.5 mm (P = .001). IgG and IgA Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG but not the IgA fraction. The frequency of plasmablasts and IL-10- and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2 years. The increased frequency of Der p 1-specific IgG4 B cells, plasmablasts, and IL-10 and dual-positive IL-10IL-1RA Breg cells significantly correlated with improved clinical symptoms over the course of AIT.

Conclusion: Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG-expressing Der p 1-specific B cells, plasmablasts, and IL-10 and/or IL-1RA Breg cells.
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http://dx.doi.org/10.1016/j.jaci.2018.10.061DOI Listing
March 2019