Publications by authors named "Stephen J Kerr"

130 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

Effect of vitamin D supplementation in patients with chronic hepatitis C after direct-acting antiviral treatment: a randomized, double-blind, placebo-controlled trial.

PeerJ 2021 9;9:e10709. Epub 2021 Feb 9.

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

Background: Replacement of vitamin D (VD) among patients with chronic hepatitis C (CHC) before viral eradication has demonstrated a protective effect on serum markers associated with hepatic fibrogenesis. We therefore hypothesized that VD may facilitate further fibrosis amelioration following curative treatment with direct-acting antivirals (DAA).

Methods: This study was a randomized, double-blind, placebo-controlled trial conducted between February 2018 and August 2018. Patients with CHC and VD deficiency were randomized in a 1:1 ratio to either receive ergicalciferol or placebo over 6 weeks. Biochemical analysis indicators, including 25-hydroxyvitamin D (25(OH)D), fibrogenic markers [(transforming growth factor beta 1 (TGF-1) and tissue inhibitors of matrix metalloproteinases 1 (TIMP-1)], and fibrolytic markers [matrix metalloproteinase 9 (MMP-9) and amino terminal type III procollagen peptide (P3NP)], were assessed at baseline and at 6 weeks. Serum 25(OH)D was analyzed by a chemiluminescence immunoassay. Serum hepatic fibrogenesis markers were measured using a quantitative sandwich enzyme-linked immunosorbent assay.

Results: Seventy-five patients with CHC and VD deficiency were randomly assigned to VD ( = 37) and placebo ( = 38) groups. At the end of the study, the mean serum 25(OH)D level had risen to a normal level in the VD group, but was still deficient in the placebo group (41.8 ±   9.1 vs. 18.1 ±  4.6 ng/mL, < 0.001). Upon restoration of the VD level, there were no significant mean differences in the change from baseline for TGF-1 (-0.6 ng/mL (95% confidence interval (95% CI) [-2.8-1.7]),  = 0.63), TIMP-1 (-5.5 ng/mL (95% CI [-26.4 -15.3]),  = 0.60), MMP-9 (122.9 ng/mL (95% CI [-69.0 -314.8]),  = 0.21), and P3NP (-0.1 ng/mL (95% CI [-2.4 -2.2]),  = 0.92) between the VD and placebo groups.

Conclusion: Short-term VD supplementation after DAA treatment in patients with CHC does not improve serum fibrogenesis markers and may not expedite the residual liver fibrosis healing process. Future studies are warranted to evaluate the long-term effect of VD supplementation on hepatic fibrosis regression.
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http://dx.doi.org/10.7717/peerj.10709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879942PMC
February 2021

Cognitive trajectories after treatment in acute HIV infection.

AIDS 2021 05;35(6):883-888

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

Objective: People with HIV continue to exhibit cognitive symptoms after suppressive antiretroviral therapy (ART). It remains unclear if initiating ART during acute HIV-1 infection (AHI) uniformly improves cognitive outcomes.

Methods: Sixty-seven individuals (96% men, median age 28 years) initiated ART immediately after AHI diagnosis and maintained viral suppression for 6 years. They underwent a four-test neuropsychological battery that measured fine motor speed and dexterity, psychomotor speed, and executive functioning at baseline (pre-ART AHI), weeks 12, 24 and 96, and annually thereafter through week 288. Performances were standardized to calculate an overall (NPZ-4) score and frequencies of impaired cognitive performance (≤-1 SD on at least two tests, or ≤-2 SD on at least one test). Group-based trajectory analysis (GBTA) was applied to identify distinct neuropsychological trajectories modelled from baseline to week 288. Posthoc analyses examined HIV-1 and demographic factors that differed between trajectory subgroups.

Results: NPZ-4 scores improved from baseline to week 96 (P < 0.001) and from weeks 96 to 288 (P < 0.001), with frequencies of impaired performance of 30, 6 and 2% at the respective time-points. The amplitude of NPZ-4 improvement throughout the period was more than 0.5 SD and beyond practice effects. GBTA identified three NPZ-4 trajectory subgroups that all showed improvement over-time. The subgroup with lowest baseline performance exhibited worse depressive symptoms at baseline (P = 0.04) and the largest improvement among the three. HIV-1 indices did not differ between the subgroups.

Conclusion: Cognitive performance improved in a sustained and stable manner after initiating ART during AHI. Largest improvements were seen in participants with worst baseline cognitive performance.
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http://dx.doi.org/10.1097/QAD.0000000000002831DOI Listing
May 2021

HIV-related enacted stigma and increase frequency of depressive symptoms among Thai and Cambodian adolescents and young adults with perinatal HIV.

Int J STD AIDS 2021 Mar 18;32(3):246-256. Epub 2020 Dec 18.

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

HIV-related enacted stigma and social problems may increase risk for depression and/or behavioral problems among adolescents and young adults with perinatal HIV(AYA-PHIV), yet few studies have explored stigma in AYA-PHIV residing in low-to-middle income regions, including Southeast Asia. We assessed HIV-related enacted stigma and social problems in AYA-PHIV who participated in the RESILIENCE study (clinicaltrials.gov identification: U19AI53741) in Thailand and Cambodia using specific questions during structured in-person interviews. Depression was measured by the Child Depression Inventory for children <15 years, or the Center for Epidemiologic Studies Depression Scales for youth ≥15 years); behavioral problems were measured by the Child Behavior Checklist (CBCL-caregiver report). Among 195 AYA-PHIV (median age 16.9 years), 25.6% reported a lifetime experience of enacted stigma, while 10.8% experienced social problems due to HIV infection. The frequency of depressive symptoms was nearly two-fold higher among AYA-PHIV with compared to those without HIV-related enacted stigma (34.7% vs. 16.0%, p = 0.005). Caregiver-reported behavioral problems were detected in 14.6% of all AYA-PHIV, with no differences between those with and without HIV-related enacted stigma. Low household income and caregiver mental health problems were independent risk factors for depressive symptoms; HIV-related enacted stigma was also associated with increased risk, warranting targeted services to support AYA-PHIV.
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http://dx.doi.org/10.1177/0956462420960602DOI Listing
March 2021

CNS Complications in Adult Patients Treated With Extracorporeal Membrane Oxygenation.

Crit Care Med 2021 Feb;49(2):282-291

University of NSW, Sydney, NSW, Australia.

Objectives: To describe the incidence and outcomes of radiologically confirmed acute CNS complications in extracorporeal membrane oxygenation patients at an Australian extracorporeal membrane oxygenation referral center and identify associated patient characteristics.

Design: Retrospective cohort study.

Setting: Single-center tertiary institution.

Patients: Four-hundred twelve consecutive adult patients supported with extracorporeal membrane oxygenation from 2009 to 2017.

Results: Fifty-five patients (13.3%) had a CNS complication confirmed by CT or MRI, including ischemic stroke (7.0%), intracerebral hemorrhage (3.4%), hypoxic ischemic encephalopathy (3.6%), and spinal cord injury (1.2%). CNS complication rates in the venoarterial, venovenous, and veno-pulmonary artery extracorporeal membrane oxygenation subgroups were 18.0%, 4.6%, and 13.6%, respectively. Neurologic complications were independently associated with the use of venoarterial extracorporeal membrane oxygenation (p = 0.002) and renal replacement therapy (p = 0.04). Sixty-five percent of patients with a neurologic complication died during their hospital admission compared with 32% of patients without this complication (p < 0.001). Venoarterial extracorporeal membrane oxygenation, renal replacement therapy, and days of extracorporeal membrane oxygenation support were also associated with hospital mortality and remained so after adjustment in a multivariable regression model (p = 0.01, p < 0.001, and p = 0.003, respectively).

Conclusions: CNS complications appear to occur more frequently in patients requiring circulatory as opposed to respiratory support on extracorporeal membrane oxygenation and are independently associated with mortality. It remains unclear if these complications are causative of a poor outcome or a marker of severity of the underlying condition. Further research is required to better elucidate modifiable or preventable aspects through better patient selection and change in ongoing care.
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http://dx.doi.org/10.1097/CCM.0000000000004789DOI Listing
February 2021

Skin manifestations after bariatric surgery.

BMC Dermatol 2020 12 9;20(1):21. Epub 2020 Dec 9.

Division of Dermatology, Department of Medicine, Faculty of Medicine, Skin and Allergy Research Unit, Chulalongkorn University, 1873 Rama IV Road, Pathumwan, Bangkok, 10330, Thailand.

Background: Skin signs observed in morbid obesity may change as the weight reduces, especially post-bariatric surgery (BaS). Data concerning the skin findings exclusively in post-BaS patients remain limited.

Methods: Seventy post-BaS patients were examined for cutaneous abnormalities. The patients were divided into those with successful weight loss (% excessive body weight loss (EBWL) of at least 50%) and a non-successful group (%EBWL < 50%).

Results: Forty-six patients with successful weight loss demonstrated a significantly lower prevalence of acanthosis nigricans on the neck, axillae and inguinal areas, keratosis pilaris (KP) and pebble fingers. However, a higher prevalence of alopecia was observed. After adjustment with patients' factors, KP (adjusted odds ratio (aOR) = 0.21, 95%CI 0.06-0.74, p = 0.02) and pebble fingers (aOR = 0.09, 95%CI 0.01-0.89, p = 0.04) remained significantly less likely in patients with successful weight loss. Laboratory results comparing pre- and post-surgery values revealed significant decreases in fasting plasma glucose, hemoglobin A1c, and triglyceride and an increase of high-density lipoproteins in both groups. However, significant decreases of liver aminotransferases (AST and ALT) were observed only in the successful group (p = 0.04, 0.003). Nonetheless, a decrease in vitamin B12 (p = 0.01) was observed in the successful group.

Conclusion: Weight loss after BaS provided an improvement for metabolic profiles. Successful weight reduction resulted in better skin improvement. However, nutritional supplements may be necessary.

Trial Registration: Thai Clinical Trials Registry TCTR20171003002 . Registered October 3. 2017, retrospectively registered.
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http://dx.doi.org/10.1186/s12895-020-00120-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726855PMC
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

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

Serum miRNA125a-5p, miR-125b-5p, and miR-433-5p as biomarkers to differentiate between posterior circulation stroke and peripheral vertigo.

BMC Neurol 2020 Oct 10;20(1):372. Epub 2020 Oct 10.

Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Bangkok, 10330, Thailand.

Background: Acute vertigo is a common presentation of inner ear disease. However, it can also be caused by more serious conditions, especially posterior circulation stroke. Differentiating between these two conditions by clinical presentations and imaging studies during the acute phase can be challenging. This study aimed to identify serum microRNA (miRNA) candidates that could differentiate between posterior circulation stroke and peripheral vertigo, among patients presenting with acute vertigo.

Methods: Serum levels of six miRNAs including miR-125a-5p, miR-125b-5p, miR-143-3p, miR-342-3p, miR-376a-3p, and miR-433-5p were evaluated. Using quantitative reverse-transcription polymerase chain reaction (RT-qPCR), the serum miRNAs were assessed in the acute phase and at a 90 day follow-up visit.

Results: A total of 58 patients with posterior circulation stroke (n = 23) and peripheral vertigo (n = 35) were included in the study. Serum miR-125a-5p (P = 0.001), miR-125b-5p (P <  0.001), miR-143-3p (P = 0.014) and miR-433-5p (P = 0.0056) were present at significantly higher levels in the acute phase, in the patients with posterior circulation infarction. Based on the area under the receiver operating characteristic curve (AUROC) only miR-125a-5p (0.75), miR-125b-5p(0.77), and miR-433-5p (0.71) had an acceptable discriminative ability to differentiate between the central and peripheral vertigo. A combination of miRNAs revealed no significant improvement of AUROC when compared to single miRNAs.

Conclusion: This study demonstrated the potential of serum miR-125a-5p, miR-125b-5p, and miR-433-5p as biomarkers to assist in the diagnosis of posterior circulation infarction among patients presenting with acute vertigo.
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http://dx.doi.org/10.1186/s12883-020-01946-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547489PMC
October 2020

Increased Burden of Concordant and Sequential Anogenital Human Papillomavirus Infections Among Asian Young Adult Women With Perinatally Acquired HIV Compared With HIV-Negative Peers.

Sex Transm Dis 2021 Mar;48(3):200-205

Department of Global Health, Amsterdam University Medical Centers, University of Amsterdam, and Amsterdam Institute for Global Health and Development.

Background: Youth with perinatally acquired HIV (YPHIV) are at higher risk for anogenital human papillomavirus (HPV) infection.

Methods: We enrolled a cohort of YPHIV and HIV-negative youth in Thailand and Vietnam, matched by age and lifetime sex partners, and followed them up for 144 weeks (to 2017). Participants had annual pelvic examinations with samples taken for HPV genotyping. Concordant infection was simultaneous HPV detection in multiple anogenital compartments (cervical, vaginal, anal); sequential infection was when the same type was found in successive compartments (cervicovaginal to/from anal). Generalized estimating equations were used to assess factors associated with concordant infection, and Cox regression was used to assess factors associated with sequential infection.

Results: A total of 93 YPHIV and 99 HIV-negative women were enrolled, with a median age of 19 years (interquartile range, 18-20 years). High-risk anogenital HPV infection was ever detected in 76 (82%) YPHIV and 66 (67%) HIV-negative youth during follow-up. Concordant anogenital high-risk HPV infection was found in 62 (66%) YPHIV versus 44 (34%) HIV-negative youth. Sequential cervicovaginal to anal high-risk HPV infection occurred in 20 YPHIV versus 5 HIV-negative youth, with an incidence rate of 9.76 (6.30-15.13) versus 2.24 (0.93-5.38) per 100 person-years. Anal to cervicovaginal infection occurred in 4 YPHIV versus 0 HIV-negative women, with an incidence rate of 1.78 (0.67-4.75) per 100 person-years. Perinatally acquired HIV was the one factor independently associated with both concordant and sequential high-risk HPV infection.

Conclusions: Children and adolescents with perinatally acquired HIV should be prioritized for HPV vaccination, and cervical cancer screening should be part of routine HIV care for sexually active YPHIV.
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http://dx.doi.org/10.1097/OLQ.0000000000001294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867588PMC
March 2021

State of the Mind: Growing up with HIV.

Paediatr Drugs 2020 Oct;22(5):511-524

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

Human immunodeficiency virus (HIV) is a neurotropic virus that has a detrimental impact on the developing central nervous system (CNS) of children growing up with perinatal HIV (PHIV) due to a combination of pathophysiological processes related to direct viral cytopathic effects and immune activation. This leads to a spectrum of neurocognitive impairment ranging from severe encephalopathy to subtle domain-specific cognitive impairments, as well as psychological disorders that are compounded by HIV-related stigma and sociodemographic factors that disproportionately affect PHIV children. Early commencement and consistent use of combination antiretroviral therapy (cART) has resulted in a dramatic improvement in neuropsychological outcomes for PHIV children; however, they remain vulnerable to cognitive impairment and psychological disorders, as evidenced by imaging findings, randomised clinical trials and observational studies. An optimal neuroprotective cART regimen remains elusive in children, but systemic viral suppression, regular neurocognitive and psychological screening and ready access to neuropsychological management strategies are key components for optimising neuropsychological outcomes. However, a lack of standardised and validated screening tools, particularly in resource-limited settings, hinders a precise understanding of the nature, prevalence and associations between neuropsychological symptomatology and HIV health. This article reviews the natural history, cellular pathophysiology and structural and functional imaging findings for children growing up with HIV, as well as summarising management strategies related to antiretroviral therapy, screening tools and specific interventions for neurocognitive impairments and psychological disorders.
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http://dx.doi.org/10.1007/s40272-020-00415-1DOI Listing
October 2020

Incidence, Persistence, and Factors Associated With HPV Infection Among Male Adolescents With and Without Perinatally Acquired HIV Infection.

J Acquir Immune Defic Syndr 2020 12;85(5):553-560

Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Infection with high-risk human papillomavirus (HR-HPV) has been shown to be more prevalent and persistent in female adolescents with HIV. However, data among male adolescents with perinatally acquired HIV (PHIV) are limited.

Setting: We investigated the incidence and persistence of HR-HPV in anogenital compartments and associated factors among PHIV in comparison to HIV-uninfected (HU) male adolescents in Thailand.

Methods: PHIV and HU males aged 12-24 years were enrolled. At baseline and 3 subsequent annual visits, specimens from the scrotum, penis, and anal area were obtained for HPV and other testing.

Results: From June 2013 to October 2017, 49 PHIV and 47 HU male adolescents with a median age of 18 (interquartile range 17-20) years were enrolled. PHIV had higher incidence of any HR-HPV infection than HU adolescents {33.05 [95% confidence interval (CI): 20.82 to 52.46] vs. 15.73 [95% CI: 8.18 to 30.22] per 100 person-years, P = 0.04}. The persistence of any HR-HPV genotypes (detected at ≥2 annual visits) was not different by group (PHIV 27% vs. HU 23%, P = 0.75). Having ≥3 sex partners in past 6 months (adjusted prevalence ratio 2.39, 95% CI: 1.14 to 5.05; P = 0.02) and co-infection with other sexually transmitted infections (syphilis, chlamydia, and/or gonorrhea) were associated with persistent HR-HPV infection (adjusted prevalence ratio 6.21, 95% CI: 2.87 to 13.41; P < 0.001).

Conclusions: Thai PHIV male adolescents had a higher incidence of HR-HPV infection than those without HIV. Having multiple sex partners and co-infection with sexually transmitted infections was associated with persistent HR-HPV infection. These data demonstrate the need to prioritize PHIV male adolescents in routine and catch-up HPV vaccination programs.
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http://dx.doi.org/10.1097/QAI.0000000000002499DOI Listing
December 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

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

Newly Discovered Abnormal Glucose Tolerance in Patients With Acute Myocardial Infarction and Cardiovascular Outcomes: A Meta-analysis.

Diabetes Care 2020 08;43(8):1958-1966

Diabetes Division, UT Health San Antonio, and Texas Diabetes Institute, San Antonio, TX

Background: The prevalence of unrecognized abnormal glucose tolerance (AGT) and the incidence of recurrent cardiovascular (CV) events in patients with acute myocardial infarction (MI) has not been systematically evaluated.

Purpose: The purposes of this study were to define the prevalence of newly discovered AGT and examine the risk of recurrent major adverse cardiac events (MACE) and mortality in patients with acute MI.

Data Sources: Medline, Embase, Cochrane Library, and Google Scholar were searched for relevant articles.

Study Selection: Inclusion criteria included prospective studies in patients with acute MI without known history of diabetes; AGT diagnosed using fasting plasma glucose, 2-h oral glucose tolerance test, or HbA; and incidence of MACE and/or all-cause mortality in newly discovered AGT.

Data Extraction: Two investigators extracted the data. Pooled prevalence, incidence rate ratios, and hazard ratios (HRs) were calculated using random-effects models.

Data Synthesis: In 19 studies ( = 41,509, median follow-up 3.1 years), prevalence of newly discovered AGT was 48.4% (95% CI 40.2-56.6). Prediabetes had a higher mortality risk than normal glucose tolerance (NGT) (HR 1.36 [95% CI 1.13-1.63], < 0.001) and MACE (1.42 [1.20-1.68], < 0.001). Newly diagnosed diabetes had higher mortality risk than NGT (1.74 [1.48-2.05], < 0.001) and MACE (1.54 [1.23-1.93], < 0.001).

Limitations: This is not a meta-analysis of individual patient data. Time-to-event analysis and covariate-adjusted analysis cannot be conducted to examine heterogeneity reliably. Few studies reported CV death and heart failure hospitalizations.

Conclusions: Patients with acute MI have a high prevalence of newly discovered AGT. Aggressive risk reduction strategies in this population, especially in those with prediabetes, are warranted.
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http://dx.doi.org/10.2337/dc20-0059DOI Listing
August 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

Usefulness of mean number of adenomas per positive screenee for identifying meticulous endoscopists among those who achieve acceptable adenoma detection rates.

Endoscopy 2021 Apr 16;53(4):394-401. Epub 2020 Jun 16.

Centre of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Background:  Adenoma detection rate (ADR) is a quality indicator for colonoscopy. However, many missed adenomas have subsequently been identified after colonoscopies performed by endoscopists with ADR ≥ 25 %. Adenomas per positive participant (APP; mean number of adenomas detected by an endoscopist among screenees with positive findings) correlates well inversely with adenoma miss rate. This study aimed to evaluate whether APP added additional information on the detection rate for advanced adenomas (AADR) and proximal adenomas (pADR) and among endoscopists with acceptable ADRs (≥ 25 %).

Methods:  A total of 47 endoscopists performed 7339 screening colonoscopies that were retrospectively reviewed. Using a cutoff APP value of 2.0, endoscopist performance was classified as high or low APP. Endoscopist ADRs were also classified as acceptable (25 % - 29 %), high standard (30 % - 39 %) and aspirational (≥ 40 %). Generalized linear models were used to assess the relationship between AADR or pADR, and ADR and APP, after adjusting for potential confounders.

Results:  After adjusting for endoscopist performance and patient characteristics, endoscopists with high APP had a significant 2.1 percentage point increase in AADR (95 %CI 0.3 to 3.9;  = 0.02) and a 2.1 percentage point increase in pADR (95 %CI - 0.8 to 5.1;  = 0.15) compared to endoscopists with low APP. In total, 11 (24 %), 18 (38 %), and 18 (38 %) endoscopists were classified as having acceptable, high standard, and aspirational ADRs, respectively. APP values higher than the cutoff were found in 18 %, 44 %, and 72 % of endoscopists with acceptable, high standard, and aspirational ADRs, respectively ( = 0.02).

Conclusion:  APP is helpful for identifying more meticulous endoscopists who can detect a greater number of advanced adenomas. Endoscopists who achieved an only acceptable ADR had the lowest APP.
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http://dx.doi.org/10.1055/a-1201-0226DOI Listing
April 2021

ERCP plus endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage for malignant hilar biliary obstruction: a multicenter observational open-label study.

Endoscopy 2021 Jan 8;53(1):55-62. Epub 2020 Jun 8.

Gastrointestinal Endoscopy Excellence Center and Division of Gastroenterology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Background:  Endoscopic retrograde cholangiopancreatography (ERCP) may not provide complete biliary drainage in patients with Bismuth III/IV malignant hilar biliary obstruction (MHBO). Complete biliary drainage is accomplished by adding percutaneous transhepatic biliary drainage (PTBD). We prospectively compared recurrent biliary obstruction (RBO) rates between combined ERCP and endoscopic ultrasound-guided biliary drainage (EUS-BD) vs. bilateral PTBD.

Methods:  Patients with MHBO undergoing endoscopic procedures (group A) were compared with those undergoing bilateral PTBD (group B). The primary outcome was the 3-month RBO rate.

Results:  36 patients were recruited into groups A (n = 19) and B (n = 17). Rates of technical and clinical success, and complications of group A vs. B were 84.2 % (16/19) vs. 100 % (17/17; 0.23), 78.9 % (15/19) vs. 76.5 % (13/17;  > 0.99), and 26.3 % (5/19) vs. 35.3 % (6/17;  = 0.56), respectively. Within 3 and 6 months, RBO rates of group A vs. group B were 26.7 % (4/15) vs. 88.2 % (15/17;  = 0.001) and 22.2 % (2/9) vs. 100 % (9/9;  = 0.002), respectively. At 3 months, median number of biliary reinterventions in group A was significantly lower than in group B (0 [interquartile range] 0-1 vs. 1 [1-2.5]), respectively ( < 0.001). Median time to development of RBO was longer in group A than in group B (92 [56-217] vs. 40 [13.5-57.8] days, respectively;  =  0.06).

Conclusions:  Combined ERCP and EUS procedures provided significantly lower RBO rates at 3 and 6 months vs. bilateral PTBD, with similar complication rates and no significant mortality difference.
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http://dx.doi.org/10.1055/a-1195-8197DOI Listing
January 2021

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

Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) for Prediction of Persistent AKI and Major Adverse Kidney Events.

Sci Rep 2020 05 26;10(1):8718. Epub 2020 May 26.

Division of Nephrology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

We aimed to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) can accurately predict persistent AKI, major adverse kidney events at 30 days (MAKE30) and 365 days (MAKE365) in hospitalized AKI patients. This is a retrospective study of adult patients who were admitted at King Chulalongkorn Memorial Hospital. We performed multivariable logistic regression for persistent AKI, MAKE30, and MAKE365. We developed equations for predicting MAKE30 and MAKE365 and divided the dataset into derivation and validation cohorts. uNGAL performance and predictive models were assessed using the area under the receiver operating characteristic curve (AROC). Among 1,322 patients with AKI, 76.9%, 45.1%, and 61.7% had persistent AKI, MAKE30, and MAKE365. The AROC were 0.75 (95% confidence interval[CI] 0.70-0.80), 0.66 (95%CI 0.61-0.71), and 0.64 (95%CI 0.59-0.70) for prediction of persistent AKI, MAKE30, and MAKE365 by uNGAL. The AROC in the validation dataset combining uNGAL with clinical covariates were 0.74 (95%CI 0.69-0.79) and 0.72 (95%CI 0.67-0.77) for MAKE30 and MAKE365. We demonstrated an association between uNGAL and persistent AKI, MAKE30, and MAKE365. Prediction models combining uNGAL can modestly predict MAKE30 and MAKE365. Therefore, uNGAL is a useful tool for improving AKI risk stratification.
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http://dx.doi.org/10.1038/s41598-020-65764-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250906PMC
May 2020

The Effects of a Standardized Extract of on Postlaser Resurfacing Wound Healing on the Face: A Split-Face, Double-Blind, Randomized, Placebo-Controlled Trial.

J Altern Complement Med 2020 Jun 20;26(6):529-536. Epub 2020 Apr 20.

Preclinical Pharmacokinetics and Interspecies Scaling for Drug Development Research Unit, Chulalongkorn University, Bangkok, Thailand.

, a medicinal plant, has been used traditionally to promote wound healing. Its efficacy on promoting postlaser resurfacing wound healing is lacking. Thirty individuals with facial acne scars underwent a treatment with 2940 nm Er:YAG laser. Half side of the face was randomized to receive 0.05% w/w ECa 233 gel, a standardized extract of , and the other half a placebo gel. The gels were applied four times daily for 7 days then twice daily for 3 months. Erythema, melanin, and texture index (TI) from Antera3D, and skin biophysics were obtained at baseline, days 2, 4, and 7, then every 2 weeks for the first month, and every month for 3 months. Three blinded dermatologists assessed the photographs and provided a grading scale of wound appearances. The ECa 233 treated side exhibited significantly less erythema index over total follow-up by 0.03 U (coefficient = -0.03 [95% CI -0.06 to -0.0006];  = 0.046). In keeping with the physicians' assessment that showed significantly higher improvements in skin erythema at days 2, 4, and 7 ( = 0.009, 0.0061, 0.012), crusting at days 2 ( = 0.02), and general wound appearance at days 2, 4, and 7 ( = 0.008, 0.001, 0.044), TI showed a trend toward better outcome in the ECa 233 group. Skin biophysics did not differ between the two groups. ECa 233 might be an option for postlaser treatment to improve wound appearance.
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http://dx.doi.org/10.1089/acm.2019.0325DOI Listing
June 2020

A newly designed duodenoscope with detachable distal cap significantly reduces organic residue contamination after reprocessing.

Endoscopy 2020 09 16;52(9):754-760. Epub 2020 Apr 16.

Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Background: A newly designed duodenoscope with detachable distal cap may reduce bacterial contamination by allowing better access to the elevator. We compared bacterial contamination and organic residue evaluated by rapid adenosine triphosphate (ATP) test and culture from duodenoscopes with detachable vs. fixed distal caps after high-level disinfection (HLD).

Methods: During December 2018-April 2019, 108 used newly designed duodenoscopes were enrolled. In group A (n = 54), the distal cap of the duodenoscope was detached before manual cleaning. In group B (n = 54), the distal cap was not detached. After HLD, samples were collected from the elevator, submitted for culture, and evaluated using the ATP test, using the cutoff value of 40 relative light units (RLUs).

Results: After HLD, the proportion of potential bacterial contamination and organic residue in group A was significantly lower than in group B (37.0 % vs. 75.9 %;  < 0.001; relative risk 0.49, 95 % confidence interval 0.33-0.71), and also confirmed by median ATP values (45.2 vs. 141.0 RLU;  < 0.001). In group B, one sample culture was positive for nonpathogenic bacteria. Pathogenic bacteria were not found in any culture from either group.

Conclusions: The detachable distal cap was more effective at eliminating bacterial contamination and reducing organic residue than a fixed cap. Nonpathogenic bacteria were detected in the fixed cap group after reprocessing. The ATP test with 40 RLU cutoff is a practical method to ensure the cleanliness of duodenoscope reprocessing without the need to wait for bacterial culture results.
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http://dx.doi.org/10.1055/a-1145-3562DOI Listing
September 2020

Prevalence of High-risk Nonavalent Vaccine-type Human Papillomavirus Infection Among Unvaccinated, Sexually Active Asian Female Adolescents With and Without Perinatally Acquired HIV Infection.

Pediatr Infect Dis J 2020 07;39(7):615-619

From the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: We studied the prevalence of 7, high-risk human papillomavirus (HPV) types in the nonavalent vaccine (HRVT-7: HPV 16, 18, 31, 33, 45, 52, 58) among vaccine-naïve, sexually active Asian female adolescents with and without perinatally acquired HIV infection (PHIV).

Methods: PHIV female adolescents 12-24 years of age and HIV-uninfected controls matched by age and number of lifetime sex partners were enrolled in a 3-year observational cohort study in Thailand and Vietnam. Samples from the oral cavity, anus, cervix and vagina were collected for HRVT-7 HPV genotyping, and serum collected for HPV 16 and 18 antibody testing. Baseline data were analyzed using multivariable logistic regression.

Results: We included 93 PHIV (median CD4 593 cells/mm, 62% with HIV RNA suppression) and 99 HIV-uninfected adolescents (median lifetime sex partners 2). The overall prevalence of HRVT-7 infection was 53% in PHIV and 49% in HIV-uninfected adolescents (P = 0.66). Cervical HRVT-7 DNA was detected more frequently in PHIV than HIV-uninfected adolescents (37% vs. 23%, P = 0.04). Overall, more lifetime partners [≥3 vs. 1; odds ratio (OR) 2.99 (1.38-6.51), P = 0.02] and having other sexually transmitted infections [OR 3.30 (1.51-7.21), P = 0.003] increased the risk of HRVT-7 infection and/or positive HPV 16/18 antibodies; while detectable HIV RNA [OR 2.78 (1.05-7.36), P = 0.04] increased the risk among PHIV adolescents.

Conclusions: Half of sexually active Asian female adolescents, regardless of HIV infection, had already acquired HRVT-7 infection. This underscores the need for earlier access to HPV vaccine in the region.
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http://dx.doi.org/10.1097/INF.0000000000002659DOI Listing
July 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

Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study.

Clin Infect Dis 2021 Feb;72(3):396-402

PREVENTION, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2).

Methods: Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT).

Results: The median (interquartile range) age and body mass index were 25.5 (22.5-31.0) years and 20.6 (19.3-23.1) kg/m2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours (C24), respectively: 0.72 (90% confidence interval, .64-.81; P < .001), 0.81 (.72-.92; P = .006), and 0.64 (.50-.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C24, and EFV C24: 0.86 (90% confidence interval, .80-.93; P = .002), 0.83 (.75-.93; P = .006), and 0.91 (.85-.97; P = .02).

Conclusions: Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens.
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http://dx.doi.org/10.1093/cid/ciaa038DOI Listing
February 2021

Diagnostic performance of different cholangioscopes in patients with biliary strictures: a systematic review.

Endoscopy 2020 03 10;52(3):174-185. Epub 2020 Jan 10.

Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.

Background: Cholangioscopy provides direct intraductual imaging, which can enhance diagnostic efficacy during endoscopic retrograde cholangiopancreatography in patients with biliary strictures. This study aimed to review the diagnostic yield of different cholangioscopes for the diagnosis of malignant biliary stricture (MBS).

Methods: A comprehensive literature review was performed. Full papers of prospective studies using any type of peroral cholangioscope (POC) were included without language restriction. The primary outcomes were sensitivity, specificity, and accuracy of various POCs to diagnose MBS.

Results: Data from 20 published articles, involving 1141 patients, were extracted. Overall sensitivities of POCs for diagnosing MBS were higher for the diagnosis made under visual impression compared with those from cholangioscopy-guided biopsy (67 % - 100 % vs. 38 % - 100 %), whereas the overall specificities were generally high and comparable (73 % - 100 % vs. 75 % - 100 %). Newer video cholangioscopes (digital single-operator POC [digital SOC], direct POC) with the exception of video dual-operator mother - baby POC (video DOC), provided better sensitivity of cholangioscopy-guided biopsy compared with fiberoptic scopes (digital SOC 80 % - 85 %, direct POC 80 % - 100 %, video DOC 38 % - 100 %, and fiberoptic SOC 49 % - 100 %, respectively). Among these video cholangioscopes, the digital SOC provided the highest technical success rate, at 100 %.

Conclusions: POCs enhanced the diagnostic yield for diagnosis of MBS. Compared with fiberoptic POCs that only provide good image impression, the digital SOC and direct POC were good at both image impression and cholangioscopy-guided biopsy to diagnose MBS. To ensure high technical success for MBS diagnosis, the digital SOC is a good option.
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http://dx.doi.org/10.1055/a-1083-6105DOI Listing
March 2020

Machine-learning classification of neurocognitive performance in children with perinatal HIV initiating de novo antiretroviral therapy.

AIDS 2020 04;34(5):737-748

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

Objective: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV).

Design: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV.

Methods: Two hundred and eighty-five children (ages 2-14 years at baseline; Mage = 6.4 years) with pHIV in Southeast Asia underwent neurocognitive assessment at study enrollment and twice annually thereafter for an average of 5.4 years. Neurocognitive slopes were modeled to establish two subgroups [above (n = 145) and below average (n = 140) trajectories). Gradient-boosted multivariate regressions (GBM) with five-fold cross validation were conducted to examine baseline (pre-ART) and longitudinal predictive features derived from demographic, HIV disease, immune, mental health, and physical health indices (i.e. complete blood count [CBC]).

Results: The baseline GBM established a classifier of neurocognitive group designation with an average AUC of 79% built from HIV disease severity and immune markers. GBM analysis of longitudinal predictors with and without interactions improved the average AUC to 87 and 90%, respectively. Mental health problems and hematocrit levels also emerged as salient features in the longitudinal models, with novel interactions between mental health problems and both CD4 cell count and hematocrit levels. Average AUCs derived from each GBM model were higher than results obtained using logistic regression.

Conclusion: Our findings support the feasibility of machine learning to identify children with pHIV at risk for suboptimal neurocognitive development. Results also suggest that interactions between HIV disease and mental health problems are early antecedents to neurocognitive difficulties in later childhood among youth with pHIV.
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http://dx.doi.org/10.1097/QAD.0000000000002471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072001PMC
April 2020