Publications by authors named "Sasiwimol Ubolyam"

65 Publications

Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features.

mBio 2021 03 9;12(2). Epub 2021 Mar 9.

Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA

Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy (ART) is interrupted. The kinetics of viral rebound, specifically the time until plasma virus becomes detectable, differ quite substantially between individuals, and associations with virological and immunological factors have been suggested. Standard clinical measures, like CD4 T-cell counts and plasma HIV RNA levels, however, are poor predictive markers. Antibody features, including Fc functionality and Fc glycosylation have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we analyzed HIV-specific antibody quantities and qualitative differences like antibody-mediated functions, Fc gamma receptor (FcγR) binding, and IgG Fc glycosylation as well as cytokine profiles and cellular HIV DNA and RNA levels in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders (≤4 weeks versus >4 weeks) and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. Specifically, individuals with early viral rebound exhibited higher levels of total HIV-specific IgGs carrying inflammatory Fc glycans, while delayed rebounders showed an enrichment of highly functional antibodies. Overall, only four features, including enhanced antibody-mediated NK cell activation in delayed rebounders, were necessary to discriminate the groups. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future ATI studies. Plasma viremia reoccurs in most HIV-infected individuals once antiretroviral therapy is interrupted, and interindividual differences in the kinetics of viral rebound have been associated with virological and immunological factors. Antibody features, including Fc functionality and Fc glycosylation, have been identified as sensitive surrogates for disease activity in multiple diseases. Here, we systematically analyzed HIV-specific antibody quantities and qualitative differences in 23 ART-suppressed individuals prior to undergoing an analytical ART interruption (ATI). We found that antibodies with distinct functional properties and Fc glycan signatures separated individuals into early and delayed viral rebounders and tracked with levels of inflammatory cytokines and transcriptional activity of the viral reservoir. These data suggest that antibody features can be used as sensitive indicators of HIV disease activity and could be included in future HIV eradication studies.
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http://dx.doi.org/10.1128/mBio.00170-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092214PMC
March 2021

Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection.

AIDS 2021 04;35(5):777-782

Yale School of Medicine, New Haven, Connecticut, USA.

Objective: Despite suppression of HIV-1 replication in the periphery by antiretroviral therapy (ART), up to 10% of treated individuals have quantifiable HIV-1 in the CSF, termed CSF escape. CSF escape may be asymptomatic but has also been linked to progressive neurological disease, and may indicate persistence of HIV in the central nervous system (CNS). CSF escape has not yet been assessed after initiation of ART during acute HIV-1 infection (AHI).

Design: Prospective cohort study.

Setting: Major voluntary counseling and testing site in Bangkok, Thailand.

Participants: Participants identified and initiated on ART during AHI who received an optional study lumbar puncture at pre-ART baseline or after 24 or 96 weeks of ART.

Main Outcome Measures: Paired levels of CSF and plasma HIV-1 RNA, with CSF greater than plasma HIV-1 RNA defined as CSF escape.

Results: Two hundred and four participants had paired blood and CSF sampling in at least one visit at baseline, week 24, or week 96. Twenty-nine participants had CSF sampling at all three visits. CSF escape was detected in 1/90 at week 24 (CSF HIV-1 RNA 2.50 log10 copies/ml, plasma HIV-1 RNA <50 copies/ml), and 0/55 at week 96.

Conclusion: Although levels of CSF HIV-1 RNA in untreated AHI are high, initiating treatment during AHI results in a very low rate of CSF escape in the first 2 years of treatment. Early treatment may improve control of HIV-1 within the CNS compared with treatment during chronic infection, which may have implications for long-term neurological outcomes and CNS HIV-1 persistence.
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http://dx.doi.org/10.1097/QAD.0000000000002786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969409PMC
April 2021

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

Inflammatory Biomarkers Do Not Differ Between Persistently Seronegative vs Seropositive People With HIV After Treatment in Early Acute HIV Infection.

Open Forum Infect Dis 2020 Sep 26;7(9):ofaa383. Epub 2020 Aug 26.

HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Persistent viral activity may cause enduring seropositivity and inflammation in treated people with HIV (PWH). We compared inflammatory biomarkers between early treated PWH who remained seronegative or seroconverted and found similar levels of D-dimer, soluble cluster of differentiation 14, C-reactive protein, and interleukin-6, indicating that seronegativity does not affect chronic inflammation in early treated PWH.
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http://dx.doi.org/10.1093/ofid/ofaa383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519777PMC
September 2020

Determinants of suboptimal CD4 T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV-1 infection.

J Int AIDS Soc 2020 09;23(9):e25585

Yale School of Medicine, New Haven, CT, USA.

Introduction: Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI).

Methods: Participants who started ART in Fiebig I to V AHI with ≥48 weeks of continuous documented HIV-RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm ), intermediate immune recovery (IIR; 350 ≤ CD4 < 500) and complete immune recovery (CIR; CD4 ≥ 500). Clinical and laboratory parameters were assessed at pre-ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks.

Results: Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post-exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre-ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8 T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL-6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices.

Conclusions: Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre-ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment.
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http://dx.doi.org/10.1002/jia2.25585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507109PMC
September 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

Dosage Optimization of Efavirenz Based on a Population Pharmacokinetic-Pharmacogenetic Model of HIV-infected Patients in Thailand.

Clin Ther 2020 07 22;42(7):1234-1245. Epub 2020 May 22.

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

Purpose: Efavirenz exhibits high interindividual variability in plasma concentrations, leading to unpredictable efficacy and toxicity. Polymorphism of CYP2B6 516G > T has been found to predominantly contribute to efavirenz variability. However, dosage recommendations incorporating CYP2B6 516G > T polymorphism have not been investigated in the Thai population. This study aimed to develop a population model of the pharmacokinetic properties of efavirenz, and to investigate the impact of patients' characteristics and CYP2B6 516G > T polymorphism on the pharmacokinetic properties of efavirenz. Model-based simulations were performed to provide genotype-based dosage optimization in a Thai population.

Methods: Plasma efavirenz concentrations measured at 12 h post-dose in 360 Thai HIV-infected patients with and without tuberculosis were analyzed by the nonlinear mixed-effects modeling approach. A 1-compartment model with first-order absorption and elimination was used for describing the pharmacokinetic properties of efavirenz.

Findings: The allele frequency of CYP2B6 516G > T was 34.17%. The efavirenz oral clearance were 11.9, 8.0, and 2.8 L/h in patients weighing 57 kg and having the CYP2B6 516 GG, 516 GT, and 516 TT genotypes, respectively. The use of rifampicin increased efavirenz oral clearance by 28%. The results from the simulations suggest that efavirenz dosages of 400, 300, and 100 mg once daily in Thai HIV mono-infected patients, and 800, 600, and 200 mg once daily in HIV/tuberculosis co-infected patients carrying CYP2B6 516 GG, 516 GT, and 516 TT, respectively.

Implication: The results from this study provide a rationale for efavirenz dose adjustment based on CYP2B6 516G > T polymorphism in Thai HIV-infected patients, which could help to improve treatment outcomes in this population. ClinicalTrials.gov identifier: NCT01138267.
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http://dx.doi.org/10.1016/j.clinthera.2020.04.013DOI Listing
July 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

Liver function test abnormalities in a longitudinal cohort of Thai individuals treated since acute HIV infection.

J Int AIDS Soc 2020 01;23(1):e25444

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

Introduction: Liver disease is a common cause of non-AIDS morbidity and mortality in people living with HIV (PLHIV), but the prevalence and significance of liver function test (LFT) abnormalities in early HIV infection is unknown. This study aimed to characterize LFTs in a large cohort of participants with acute HIV infection initiating immediate antiretroviral therapy (ART) and examine the association between LFTs and biomarkers of HIV infection and inflammation.

Methods: We measured LFTs at the time of HIV diagnosis and at 4, 12, 24 and 48 weeks after ART initiation in 426 Thai individuals with acute HIV infection from 2009 to 2018. A subset of individuals had data available at 96 and 144 weeks. We excluded individuals with concomitant viral hepatitis. Alanine aminotransferase (ALT) was the primary outcome of interest; values greater than 1.25 times the upper limit of normal were considered elevated. Analyses utilized descriptive statistics, non-parametric tests and multivariate logistic regression.

Results: Sixty-six of the 426 individuals (15.5%) had abnormal baseline ALT levels; the majority (43/66, 65.5%) had Grade 1 elevations. Elevated baseline ALT correlated with Fiebig stages III to V (p = 0.001) and baseline HIV RNA >6 log copies/mL (p = 0.012). Baseline elevations resolved by 48 weeks on ART in 59 of the 66 individuals (89%). ALT elevations at 24 and 48 weeks correlated with Fiebig stages I to II at diagnosis (p < 0.001), baseline plasma HIV RNA levels <6 log copies/mL (p < 0.001), abnormal baseline ALT (p < 0.001), baseline CD4 >350 cells/μL (p = 0.03) and older age (p = 0.03). Individuals initiating efavirenz-based regimens were more likely to have elevated ALT levels at 48 weeks compared with those on non-efavirenz-based regimens (p = 0.003).

Conclusions: One in six people with acute HIV infection have elevated LFTs. Clinical outcomes with ART started in acute HIV are generally good, with resolution of ALT elevations within 48 weeks on ART in most cases. These results suggest a multifactorial model for hepatic injury involving a combination of HIV-associated and ART-associated processes, which may change over time.
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http://dx.doi.org/10.1002/jia2.25444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968973PMC
January 2020

Pattern and Frequency of Seroreactivity to Routinely Used Serologic Tests in Early-Treated Infants With HIV.

J Acquir Immune Defic Syndr 2020 03;83(3):260-266

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

Background: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection.

Methods: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies.

Results: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay.

Conclusions: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.
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http://dx.doi.org/10.1097/QAI.0000000000002254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050817PMC
March 2020

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

Viral Blips After Treatment Initiation During Acute Human Immunodeficiency Virus Infection.

Clin Infect Dis 2020 06;70(12):2706-2709

US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.

Transient viral blips ≥20 copies/mL were observed in 16.9% of acutely treated adults with HIV. Blip incidence increased from 0.0 (95% CI, 0.0-2.9)/100 person-years after ART in Fiebig I to 15.9 (7.6-29.2) in Fiebig V. Increasing viral load and Fiebig stage at ART initiation were independently predictive of blips.
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http://dx.doi.org/10.1093/cid/ciz936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286371PMC
June 2020

Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection.

Nat Med 2018 07 11;24(7):923-926. Epub 2018 Jun 11.

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

Antiretroviral therapy during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption. We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following analytical treatment interruption, indicating that additional strategies are required to control or eradicate HIV.
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http://dx.doi.org/10.1038/s41591-018-0026-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092240PMC
July 2018

Intensification of antiretroviral treatment with raltegravir for pregnant women living with HIV at high risk of vertical transmission.

J Virus Erad 2018 Apr 1;4(2):61-65. Epub 2018 Apr 1.

The Thai Red Cross AIDS Research Center, Bangkok, Thailand.

 The rate of vertical HIV transmission for women at high risk of HIV transmission stands at approximately 7.6%. In the present study we describe infant infection rates in women who had received raltegravir (RAL) intensification during pregnancy to a standard three-drug antiretroviral (ART) regimen in Thailand.  This prospective cohort study enrolled HIV-1-positive pregnant women at high risk of vertical transmission, as defined by (1) ART initiation at a gestational age (GA) ≥32 weeks or (2) HIV-1 RNA >1000 copies/mL at GA of 32-38 weeks while on ART. Women received a standard three-drug ART regimen with RAL intensification (400 mg twice daily) until delivery and continued on a three-drug ART regimen after delivery. Plasma HIV-1 RNA testing was performed before intensification and at delivery. Infant HIV-1 status was determined using DNA PCR at birth, and at 1, 2 and 4 months of life.  Between February 2016 and November 2017, 154 pregnant women on ART were enrolled into the study with a median CD4 cell count and plasma HIV-1 RNA level of 382 cells/mm and 4.0 log copies/mL, respectively. The three-drug combination consisted of either a lopinavir/ritonavir- (53%) or efavirenz-based (43%) regimen. Median GA at time of RAL initiation was 34 weeks (interquartile range [IQR] 33-36) and median duration was 21 days (IQR 8-34). The proportion of women who had a plasma HIV-1 RNA <50 and <1000 copies/mL at delivery was 45% and 76%, respectively. There were six infants with HIV infection, three in utero and three peripartum. Overall vertical transmission rate was 3.9% (95% confidence interval [CI] 1.4-8.2).  The majority of high-risk pregnant women living with HIV-1 who had received RAL intensification achieved viral suppression at delivery with a relatively low rate of vertical transmission. This intensification strategy represents an option for prevention in HIV-positive women at high risk of vertical transmission.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892679PMC
April 2018

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

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

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

The study assessed and compared bacterial vaginosis (BV) prevalence in Thai women in reproductive age in four study groups - group 1, HIV-positive with copper intrauterine device (Cu-IUD); group 2, HIV-positive without Cu-IUD; group 3, HIV-negative with Cu-IUD; and group 4, HIV-negative without Cu-IUD. We conducted a cross-sectional study. BV prevalence was assessed by Nugent score and Amsel criteria. Descriptive statistics was used to present baseline characteristics; kwallis rank test - to compare variables between the four groups; logistic regression - to assess factors, related to BV prevalence. The analysis included 137 women in the four study groups with a median age of 39 years. Median BV prevalence by Nugent score was 45%, intermediate vaginal flora - 7% and normal vaginal flora - 48%. There was no statistically significant difference in the BV prevalence between the four study groups, p = 0.711. Threefold lower BV prevalence was found, assessed by Amsel criteria compared to Nugent score. Women with body mass index (BMI) < 20 had higher probability to have BV or intermediate vaginal flora, OR = 3.11, 95% CI (1.2-8.6), p = 0.025. The study found a high BV prevalence in the four study groups, related neither to HIV status, nor to Cu-IUD use. BV prevalence was associated only with low BMI. Thus, Cu-IUD could be a good contraceptive choice for HIV-positive women. Research in defining normal vaginal microbiota and improve diagnostic methods for BV should continue.
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http://dx.doi.org/10.1080/09540121.2018.1450479DOI Listing
November 2018

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

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

Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

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

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

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

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

Efficacy and safety of a once-daily single-tablet regimen of tenofovir, lamivudine, and efavirenz assessed at 144 weeks among antiretroviral-naïve and experienced HIV-1-infected Thai adults.

Int J Infect Dis 2017 Aug 13;61:89-96. Epub 2017 Jun 13.

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, 104 Ratchadamri Rd, Pathumwan, Bangkok, 10330, Thailand; Division of Allergy and Immunology, Faculty of Medicine, Chulalongkorn University, Rama IV Rd, Pathumwan, Bangkok,10330, Thailand.

Objective: To assess the efficacy and safety of a new single-tablet regimen (STR) of tenofovir disoproxil fumarate (TDF) 300mg, lamivudine (3TC) 300mg, and efavirenz (EFV) 600mg in HIV-infected Thai patients.

Methods: This was a prospective study performed for 144 weeks among 51 treatment-naïve patients and 49 experienced patients on separate tablets of TDF, 3TC, and EFV with HIV RNA<50 copies/ml. CD4, HIV RNA, liver and renal function, and lipid profiles were assessed at baseline, weeks 12, 24, and 48, and then every 24 weeks.

Results: The median baseline CD4 cell count was 512 cells/μl for treatment-experienced patients and 230 cells/μl for treatment-naïve patients. Median baseline log HIV-1 RNA for treatment-naïve subjects was 4.9 copies/ml. From the intention-to-treat (ITT) analysis, the proportion of subjects with HIV RNA <50 copies/ml at week 48, 96, and 144 was 95%, 94%, and 94%, respectively, for antiretroviral-experienced patients and 88%, 90%, and 80%, respectively, for antiretroviral-naïve patients. One virological failure at week 12 had primary drug resistance of K70R, T69D, V75L. Three serious adverse events occurred (tension headache, infective endocarditis, and cervical dysplasia) and another three discontinued the study drug due to EFV intolerance.

Conclusions: This generic STR TDF/3TC/EFV is effective and well-tolerated. These findings lend support to the use of this generic STR as first-line antiretroviral therapy in resource-limited settings.
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http://dx.doi.org/10.1016/j.ijid.2017.06.009DOI Listing
August 2017

Real-Life Clinical Practice of Using the Xpert MTB/RIF Assay in Thailand.

Clin Infect Dis 2017 May;64(suppl_2):S171-S178

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

Background: Delayed diagnosis of tuberculosis (TB) and drug-resistant TB are major challenges of TB control in Thailand. This study assessed the practicality of the Xpert MTB/RIF assay in a real-life setting with high prevalence of human immunodeficiency virus (HIV) infection and pulmonary tuberculosis (PTB).

Methods: This prospective study was conducted at 3 large tertiary care hospitals. Patients who had suspected PTB were enrolled into the study. Expectorated sputum samples were sent for staining, mycobacterial culture, and Xpert MTB/RIF.

Results: Four hundred ninety-four patients were enrolled. From 355 cases with final diagnosis of PTB, 263 (71.8%) had definite diagnosis and 92 cases had probable diagnosis. Among TB culture-positive cases, Xpert MTB/RIF had 100% and 81% sensitivity in sputum smear-positive and smear-negative groups, respectively. The specificity was 95.7%. The sensitivity and positive predictive value of Xpert MTB/RIF in culture-negative but clinically diagnosed PTB was 37.8% and 83.8%, respectively. Centrifugation was required in 59% cases with scanty sputum. Five cases were false-positive by Xpert MTB/RIF in patients with nontuberculous mycobacteria, old PTB scar, and immune reconstitution syndrome. Discordant rifampicin susceptibility results of Xpert MTB/RIF and mycobacteria growth indicator tube (MGIT) were confirmed by using rpoB gene sequencing, which raised the sensitivity of Xpert MTB/RIF in detecting rifampicin resistance to 93.8%.

Conclusions: Xpert MTB/RIF is an effective tool in diagnosing PTB but will be more cost-effective for sputum-negative patients and in settings with high prevalence of rifampicin resistance. Early diagnosis of TB results in early treatment and implementation of strategies to limit spreading of TB. Sputum centrifugation may increase the yield of Xpert MTB/RIF.
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http://dx.doi.org/10.1093/cid/cix151DOI Listing
May 2017

Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network.

Int J Infect Dis 2017 Jun 27;59:96-102. Epub 2017 Apr 27.

Department of Medicine, Faculty of Medicine, Chulalongkorn University, The King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand; HIV-NAT, The Thai Red Cross AIDS Research Centre (TRC-ARC), 104 Ratchadamri Rd, Pathumwan, Bangkok 10330, Thailand.

Objectives: To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB.

Methods: Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed.

Results: The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death.

Conclusions: This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients.
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http://dx.doi.org/10.1016/j.ijid.2017.04.017DOI Listing
June 2017

Carbohydrate, lipid, bone and inflammatory markers in HIV-positive adolescents on antiretroviral therapy and hormonal contraception.

J Virus Erad 2017 Jan 1;3(1):56-60. Epub 2017 Jan 1.

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand; SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Background: Little is known about the cumulative effect of HIV antiretroviral therapy (ART) and hormonal contraception (HC) on metabolism and inflammation in HIV-positive women.

Methods: We conducted a cross-sectional assessment of markers for carbohydrate, lipid, bone metabolism, inflammation and coagulation in HIV-positive adolescents on ART and HC (=37) versus on ART only (=51) in Thailand. The Wilcoxon rank-sum test was used to assess differences between groups.

Results: The median age was 19.5 years. Most adolescents (95%) were perinatally infected. All were on ART for a median of 9 years. HC used was progestin only (=21); combined oral contraceptive (COC) tablets (=6) for the whole study period or alternating between progestin only and COC (=10). Prevalence of any metabolic abnormalities was 99%. Four biomarkers were significantly higher with HC no HC: insulin (10.3 6.2 μU/mL, =0.002), insulin resistance (1.89 1.19 mass units, =0.005), 25-OH vitamin D (33.2 20.2 ng/mL, <0.0001) and C-terminal telopeptide (690 530 ng/L, =0.011). Triglycerides and D-dimer were significantly lower with HC (103 139 mg/dL, =0.014 and 140 155 ng/mL, =0.003, respectively). There was no relationship between the type of HC or ART and the above differences.

Conclusion: Perinatally infected HIV-positive adolescents on ART in this pilot study had a high prevalence of metabolic abnormalities. Bone turnover markers and insulin resistance were significantly higher with HC. Research on the cumulative effect of HIV, ART and HC on metabolism and inflammation in adolescents with HIV is important in order to devise strategies for preventing and mitigating long-term comorbidities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337422PMC
January 2017

Initiation of Antiretroviral Therapy During Acute HIV-1 Infection Leads to a High Rate of Nonreactive HIV Serology.

Clin Infect Dis 2016 08 17;63(4):555-61. Epub 2016 Jun 17.

South East Asia Research Collaboration with Hawaii (SEARCH) Henry M. Jackson Foundation for the Advancement of Military Medicine United States Military HIV Research Program, Bethesda, Maryland.

Background: Third- and fourth-generation immunoassays (IAs) are widely used in the diagnosis of human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) during acute HIV infection (AHI) may impact HIV-specific antibodies, with failure to develop antibody or seroreversion. We report on the ability of diagnostic tests to detect HIV-specific antibodies in Thai participants initiating ART during AHI.

Methods: Participants with detectable plasma HIV RNA but nonreactive HIV-specific immunoglobulin G, enrolled in an AHI study, were offered immediate initiation of ART. Participants were tested at initiation and at 12 and 24 weeks following treatment using standard second-, third-, and fourth-generation IAs and Western blot (WB).

Results: Participants (N = 234) initiating ART at a median of 19 days (range, 1-62 days) from HIV exposure demonstrated different frequencies of reactivity prior to and following 24 weeks of ART depending on the IA. Third-generation IA nonreactivity prior to ART was 48%, which decreased to 4% following ART (P < .001). Fourth-generation IA nonreactivity was 18% prior to ART and 17% following ART (P = .720). Negative WB results were observed in 89% and 12% of participants prior to and following 24 weeks of ART, respectively (P < .001). Seroreversion to nonreactivity during ART was observed to at least one of the tests in 20% of participants, with fourth-generation IA demonstrating the highest frequency (11%) of seroreversion.

Conclusions: HIV-specific antibodies may fail to develop and, when detected, may decline when ART is initiated during AHI. Although fourth-generation IA was the most sensitive at detecting AHI prior to ART, third-generation IA was the most sensitive during treatment.

Clinical Trials Registration: NCT00796146 and NCT00796263.
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http://dx.doi.org/10.1093/cid/ciw365DOI Listing
August 2016

High Variability of Hormonal Levels and No Clinically Relevant Interaction Between Ethinyl Estradiol, Desogestrel and Lopinavir/Ritonavir in a Small Sample of HIV-positive Adolescents.

J Acquir Immune Defic Syndr 2016 Aug;72(5):507-12

*Medical Department, The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand; †Medical Pediatric Department, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‡Research Biomarkers Core Laboratory, Irving Institute for Clinical and Translation, Columbia University Medical Center, New York, NY; §Biostatics, Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands; ‖The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ¶SEARCH, Bangkok, Thailand; and #Currently, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.

Background: We report the pharmacokinetic interactions of combined oral contraceptive (COC) containing ethinyl estradiol (EE2)/desogestrel (DSG) with lopinavir/ritonavir (LPV/r) in 16 HIV-positive adolescents.

Methods: We measured Ctrough of EE2 and etonogestrel (ENG), the active metabolite of DSG, in HIV-positives on LPV/r-based ART; Ctrough of LPV/r with and without COC; endogenous progesterone. EE2/ENG levels were compared with our own historical data of HIV-negative controls.

Results: Ctrough of EE2 and ENG varied from 3 to 57 pg/mL and from 1051 to 5000 pg/mL, respectively. The geometric mean ratios (GMR) of Ctrough in HIV-positives on LPV/r with COC versus HIV-negative controls with COC only were 0.68 (95% CI: 0.42 to 1.08) or 32% decreased (P = 0.10) for EE2; and 1.08 (95% CI: 0.73 to 1.60) or 8% increased (P = 0.68) for ENG. Endogenous progesterone was <1.0 ng/mL in all participants, consistent with anovulation. Ctrough of LPV decreased statistically insignificantly with COC and remained above the desired therapeutic minimum of 1.0 mg/L in all.

Conclusions: The study found no clinically relevant interaction between EE2/DSG and LPV/r. This was supported by suppressed ovulation, assessed by low endogenous progesterone levels in all participants; and preserved antiretroviral activity, assessed by LPV/r levels above the desired therapeutic minimum in all participants. However, the high variability of hormonal levels warrants individual monitoring and further investigation. Condom use should always be encouraged for infection prevention.
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http://dx.doi.org/10.1097/QAI.0000000000000997DOI Listing
August 2016

Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection.

J Virus Erad 2016;2:43-48

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

Background: The challenges of identifying acute HIV infection (AHI) have resulted in a lack of critical information on early AHI that constrains the development of therapeutics that are designed to eradicate HIV from the infected host.

Methods: AHI participants were recruited from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand into the RV254/SEARCH010 protocol and categorised according to Fiebig stages as follows: Fiebig I (HIV-RNA+, p24 Ag-, HIV IgM-) and Fiebig II-IV (HIV-RNA+, p24 Ag + or -, HIV IgM- or +, Western blot- or indeterminate). Proviral and viral burden and immune activation levels were compared between Fiebig stage groups at the time of AHI. CD4 and CD4/CD8 ratio were also compared between groups before and up to 96 weeks of ART.

Results: Median age was 27 years and 96% were male. Fiebig I individuals had lower median HIV-DNA in mononuclear cells from blood (3 . 190 copies/10 cells) and gut (0 . 898 copies/10 cells), and lower HIV-RNA in blood (4.2 . 6.2 log copies/mL), gut (1.7 . 3.1 log copies/mg) and cerebrospinal fluid (2.0 . 3.8 log copies/mL), when compared to Fiebig II-IV individuals (all <0.01). Median plasma sCD14 level was lower (1.1 . 1.6 μg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6 . 14.9%, both <0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig I . 0.5 pg/mL in Fiebig II-IV, >0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1 . 2.6%, >0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508 . 340 cells/mm and 1.1 . 0.7, respectively (both <0.001). After ART, CD4 cell count normalised by week 24 in Fiebig I and week 48 in Fiebig II-IV. However, CD4/CD8 ratio was lower in both groups after 96 weeks of ART compared to healthy Thais (=0.02).

Conclusions: Compared to later AHI stages, Fiebig I was associated with lower HIV burden in blood and tissue compartments, lower immune activation and higher CD4 and CD4/CD8 ratio. ART in Fiebig I-IV resulted in normalisation of CD4 cell count within the first year, supporting the benefit of early ART. However, the CD4/CD8 ratio was not normalised after 2 years of ART in all AHI stages, suggesting some degree of persistent immunological dysfunction even when ART was instituted as early as Fiebig I.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754199PMC
January 2016

Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy.

J Acquir Immune Defic Syndr 2015 Dec;70(4):393-9

*Yale University School of Medicine, New Haven, CT; †SEARCH, The Thai Red Cross AIDS Research Center, Bangkok, Thailand; ‡US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD; §Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; ‖University of California, San Francisco, CA; ¶Missouri Institute of Mental Health, University of Missouri, St. Louis, MO; #Yale Center for Analytical Sciences, New Haven, CT; and **HIV-NAT, The Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Objective: To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviral therapy (cART).

Design: Prospective study of Thai AHI participants examined at 3 and 6 months after initiation of cART.

Methods: Thirty-six AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test, Color Trails 1 & 2 (CT1, CT2), and Trail Making Test A. Raw scores were standardized to 251 age- and education-matched HIV-uninfected Thais. To account for learning effects, change in NP performance was compared with that of controls at 6 months. Analyses included multivariable regression, nonparametric repeated measures analysis of variance, and Mann-Whitney U test.

Results: Baseline NP scores for the AHI group were within normal range (z-scores range: -0.26 to -0.13). NP performance improved on CT1, CT2, and Trail Making Test A in the initial 3 months (P < 0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (P = 0.018). Participants who performed >1 SD below normative means on ≥2 tests (n = 8) exhibited higher baseline cerebrospinal fluid HIV RNA (P = 0.047) and had no improvement after cART.

Conclusions: Most AHI individuals had normal NP performance, and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance, which correlated with higher cerebrospinal fluid HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals.
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http://dx.doi.org/10.1097/QAI.0000000000000746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625393PMC
December 2015

The Association of Gender, Age, Efavirenz Use, and Hypovitaminosis D Among HIV-Infected Adults Living in the Tropics.

AIDS Res Hum Retroviruses 2016 Apr 15;32(4):317-24. Epub 2015 Oct 15.

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

Vitamin D, which is important for calcium homeostasis and bone metabolism, has several noncalcemic actions. Low vitamin D levels have been observed in HIV-infected patients from high latitudes, with consequently reduced bone mineral density (BMD), but data from the tropics are scarce. We aimed to determine the prevalence of and risk factors for hypovitaminosis D among HIV-infected patients in the tropics. This was a cross-sectional study to determine serum 25-hydroxyvitamin D [25(OH)D] levels in HIV-infected patients who attended our HIV clinic in Bangkok, Thailand from July 2010 to June 2011. Hypovitaminosis D was defined as vitamin D insufficiency and deficiency [25(OH)D 20-30 ng/ml and <20 ng/ml, respectively]. Hypovitaminosis D prevalence was calculated and risk factors were determined using multivariate logistic regression. A total of 673 HIV-infected adults were included. The median age was 41 years and 47% were females. The median body mass index (BMI) was 21.9 kg/m(2) and 93% were using antiretroviral therapy (ART), with a median (IQR) duration of 8.9 (5.0-10.4) years. Thirty-one percent were using efavirenz (EFV). The prevalence of vitamin D insufficiency and deficiency was 40.6% and 29.9%, respectively. In multivariate analysis, female gender [odds ratio: OR (95% confidence interval: 95% CI) 1.7 (1.2-2.3), p = 0.005], age >37 years [OR (95% CI) 1.6 (1.1-2.4), p = 0.01], and EFV use [OR (95% CI) 2.0 (1.3-3.2), p = 0.004] were independent predictors of hypovitaminosis D. Even in tropical areas where the sun is abundant, hypovitaminosis D is highly prevalent. Thus, treatment of low vitamin D in HIV-infected patients at high risk should not be ignored to prevent reductions in BMD and other hypovitaminosis D-related comorbidities.
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http://dx.doi.org/10.1089/AID.2015.0069DOI Listing
April 2016

Low uptake of HIV testing and no HIV positivity in stable serodiscordant heterosexual partners of long-term treated HIV-infected Thais.

AIDS Care 2015 15;27(5):587-94. Epub 2014 Dec 15.

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

The objective of this study was to characterize HIV-serodiscordant heterosexual couples and to evaluate acceptance for HIV testing and HIV prevalence in nonindex partners. We conducted a cross-sectional study with quantitative and qualitative components. Two cohorts of 1767 HIV-positive people were screened to identify heterosexual HIV-serodiscordant couples. HIV-positive partners (index) were administered a questionnaire; CD4, viral load (VL), and antiretroviral therapy (ART) history were gathered from clinical records. HIV-negative/unknown status partners (nonindex) were invited for a similar questionnaire and HIV testing. In-depth interviews with three HIV-serodiscordant couples were conducted. Two hundred and ninety-seven index partners agreed to enroll in this study. The median duration of the relationship was 10 years, and 81% were sexually active. All but two index partners were on ART, and 98% had VL < 1000 copies/mL. Only 111 (37%) nonindex partners came for HIV testing, and all of them tested HIV-negative. In addition, only 41% of nonindex partners had HIV testing in the last one year. The main reasons for the nonindex partners not to come for HIV testing were "no interest" (n = 117, 63%) and "nondisclosure of HIV status" (n = 46, 25%). The latter was substantiated and explained by the qualitative outcome of this study, suggesting relation to stigma against HIV-positive people. Our results support the WHO recommendation for starting ART for treatment and prevention in HIV-serodiscordant couples at any CD4 count. Furthermore, we recommend the dissemination of data showing that no HIV transmission in heterosexual couples through sex practice has been observed provided VL is suppressed. This could be a powerful tool for effective fight against stigma and self-stigma in people living with HIV.
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http://dx.doi.org/10.1080/09540121.2014.989485DOI Listing
August 2015

Significant decrease of ethinylestradiol with nevirapine, and of etonogestrel with efavirenz in HIV-positive women.

J Acquir Immune Defic Syndr 2014 Jun;66(2):e50-2

*The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand †The Thai Red Cross AIDS Research Centre, Bangkok, Thailand ‡SEARCH, Bangkok, Thailand §The Kirby Institute, The University of New South Wales, Sydney, Australia ‖Irving Institute for Clinical and Translation, Research Biomarkers Core Laboratory, Columbia University Medical Center, New York, NY ¶Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand #Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1097/QAI.0000000000000134DOI Listing
June 2014

Incomplete restoration of Mycobacterium tuberculosis-specific-CD4 T cell responses despite antiretroviral therapy.

J Infect 2014 Apr 8;68(4):344-54. Epub 2013 Dec 8.

The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Sydney, Australia.

Objectives: Despite antiretroviral therapy (ART), HIV-infected persons have increased risk of active tuberculosis (TB). PPD and combined ESAT-6 and CFP-10-specific-CD4 (EC-Sp-CD4) responses were examined over 96 weeks.

Methods: HIV-infected, ART-naive Thai adults with CD4 T cell count ≤350 cells/μL starting ART were assessed at baseline, wk4, 8, 12, 24, 48 and 96. PPD and EC-Sp-CD4 T cells were detected by CD25/CD134 co-expression after stimulation with antigens.

Results: Fifty subjects were enrolled, 39 were male, median age 32 yrs, median baseline CD4 T cell count 186 cells/μL and plasma HIV-viral-load 4.9log10 copies/mL. Seventeen were TB-sensitised. At baseline, 25 had positive PPD and 15 had positive EC-Sp-CD4 response. CD4 T cell count <100 cells/μL was less (P = 0.005) and TB-sensitisation was more likely (P = 0.013) to be associated with positive baseline PPD-Sp-CD4 response. At wk4, the number of subjects with positive PPD-Sp-CD4 response rose to 35 (P = 0.021). Mean PPD-Sp-CD4 T cells increased at wk4 (P = 0.017) in patients not classified as TB-sensitised. The number of subjects with positive EC-Sp-CD4 response did not change significantly post ART. In TB-sensitised patients, mean EC-Sp-CD4 T cells declined to below baseline from wk12 (P = 0.010) onwards. EC-Sp-CD4 responses were undetectable in 3 out of 17 TB-sensitised patients.

Conclusions: Restoration of responses to TB-antigens was incomplete and inconsistent under the employed experimental conditions and may account for persistent increased risk of TB despite ART.
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http://dx.doi.org/10.1016/j.jinf.2013.11.016DOI Listing
April 2014