Publications by authors named "Archawin Rojanawiwat"

25 Publications

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Deficiency of mannose-binding lectin is a risk of Pneumocystis jirovecii pneumonia in a natural history cohort of people living with HIV/AIDS in Northern Thailand.

PLoS One 2020 23;15(12):e0242438. Epub 2020 Dec 23.

Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Background: Mannose-binding lectin (MBL) plays a pivotal role in innate immunity; however, its impact on susceptibility to opportunistic infections (OIs) has not yet been examined in a natural history cohort of people living with HIV/AIDS.

Methods: We used archived samples to analyze the association between MBL expression types and risk of major OIs including Pneumocystis jirovecii pneumonia (PCP), cryptococcosis, talaromycosis, toxoplasmosis, and tuberculosis in a prospective cohort in Northern Thailand conducted from 1 July 2000 to 15 October 2002 before the national antiretroviral treatment programme was launched.

Results: Of 632 patients, PCP was diagnosed in 96 (15.2%) patients, including 45 patients with new episodes during the follow-up period (1006.5 person-years). The total history of PCP was significantly associated with low MBL expression type: high/intermediate (81/587, 13.8%), low (10/33, 30.3%) and deficient (5/12, 41.7%) (p = 0.001), whereas the history of other OIs showed no relation with any MBL expression type. Kaplan-Meier analysis (n = 569; log-rank p = 0.011) and Cox's proportional hazards model revealed that deficient genotype dramatically increased the risk of PCP, which is independent upon sex, age, CD4 count, HIV-1 viral load and hepatitis B and C status (adjusted hazard ratio 7.93, 95% confidence interval 2.19-28.67, p = 0.002).

Conclusions: Deficiency of MBL expression is a strong risk factor determining the incidence of PCP but not other major OIs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242438PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757797PMC
January 2021

Implementation of an active case management network to identify HIV-positive infants and accelerate the initiation of antiretroviral therapy, Thailand 2015 to 2018.

J Int AIDS Soc 2020 02;23(2):e25450

Bureau of AIDS, TB and STIs, Ministry of Public Health, Nonthaburi, Thailand.

Introduction: Early initiation of antiretroviral therapy (ART) can reduce HIV-related morbidity and mortality in HIV-positive infants. We implemented an Active Case Management Network to promote early ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre-ACC).

Methods: Thailand's 2014 HIV Treatment Guidelines recommend that HIV-exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV-positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time-to-ART initiation.

Results: The uptake of EID increased from 64% (pre-ACC) to >95% in 2018 (ACC). The number of HIV-positive infants born declined from 429 cases (pre-ACC) to 267 cases (ACC). Median age at the first-positive PCR declined from 75 days (pre-ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV-positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001).

Conclusions: An innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case-managed PCR notification and follow-up, may speed ART initiation in other settings.
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http://dx.doi.org/10.1002/jia2.25450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046526PMC
February 2020

Impact of HLA Allele-KIR Pairs on Disease Outcome in HIV-Infected Thai Population.

J Acquir Immune Defic Syndr 2018 07;78(3):356-361

National Institute of Health, Ministry of Public Health, Nonthaburi, Thailand.

Background: Class I human leukocyte antigen (HLA) molecules contribute to HIV control through antigen presentation to both cytotoxic T lymphocytes and natural killer cells. Contribution of cytotoxic T lymphocytes to HIV clinical outcome by HLA alleles has been well studied. However, reports about the role of natural killer cells in HIV clinical outcome, particularly, about the effect of HLA-killer immunoglobulin-like receptor (KIR) pairs, remain incomplete.

Methods: The effects of HLA allele-KIR pairs on HIV clinical outcome were statistically analyzed in a Thai cohort of treatment-naive chronically infected population (n = 209).

Results: Five HLA allele-KIR pairs scored significantly in viral load (VL) differences. Among them, opposing effects on VL were identified among subjects expressing KIR2DL2 ligands within the HLA-C1 group: higher VL in individuals expressing HLA-B*46:01+KIR2DL2+ compared with individuals without KIR (HLA-B*46:01+KIR2DL2-) (5.0 vs 4.6 log10 copies/mL, P = 0.02), in HLA-C*01:02+KIR2DL2+ (5.0 vs 4.6 log10 copies/mL; P = 0.02), and lower VL in HLA-C*12:03+KIR2DL2+ (4.3 vs 5.6 log10 copies/mL; P = 0.01). In the longitudinal analysis of a ten-year follow-up, HLA-B*46:01+KIR2DL2+ve subjects also had a higher mortality rate compared with the subjects without that pair, independent of variables including antiretroviral treatment, as well as CD4 T-cell count, sex, and age (adjusted hazard ratio 5.9, P = 0.02).

Conclusion: We identified several HLA allele-KIR pairs associated with clinical outcome differences including opposing effects on VL within 1 HLA group with the same KIR. Among them, HLA-B*46:01 emerged in Southeast Asia about 50,000 years ago and is now the most prevalent HLA-B allele in that area. These findings highlight that each endemic area has unique features of anti-HIV innate immunity that impact clinical outcome.
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http://dx.doi.org/10.1097/QAI.0000000000001676DOI Listing
July 2018

Regional Differences in the Prevalence of Major Opportunistic Infections among Antiretroviral-Naïve Human Immunodeficiency Virus Patients in Japan, Northern Thailand, Northern Vietnam, and the Philippines.

Am J Trop Med Hyg 2017 Jul;97(1):49-56

Institute of Tropical Medicine (NEKKEN), Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan.

To identify regional differences in the distribution of opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in Asia, the medical records of antiretroviral therapy (ART)-naïve patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: Nagoya Medical Center (NMC, Nagoya, Japan), Lampang Hospital (LPH, Lampang, northern Thailand), Bach Mai Hospital (BMH, Hanoi, northern Vietnam), and Philippine General Hospital (PGH, Manila, Philippines). Logistic regression analyses were performed to identify associations between country of origin and risk of major OIs. In total, 1,505 patients were included: NMC, = 365; LPH, = 442; BMH, = 384; and PGH, = 314. The median age was 32 years, and 73.3% of all patients were male. The median CD4 count was 200 cells/μL. Most patients at NMC and PGH were men who have sex with men. Injection drug users were most common at BMH (35.7%). (TB) was most common at PGH ( = 75) but was rare at NMC ( = 4). pneumonia (PCP) prevalence was highest at NMC ( = 74) and lowest at BMH ( = 13). Multivariable logistic regression showed increased odds of TB at PGH (adjusted odds ratio [aOR] = 42.2, 95% confidence interval [CI] = 14.6-122.1), BMH (aOR = 12.6, CI = 3.9-40.3), and LPH (aOR = 6.6, CI = 2.1-21.1) but decreased odds of PCP at BMH (aOR = 0.1, CI = 0.04-0.2) and LPH (aOR = 0.2, CI = 0.1-0.4) compared with those at NMC. The cryptococcosis risk was increased at LPH (aOR = 6.2, CI = 0.9-41.0) compared with that at NMC. Cytomegalovirus (CMV) retinitis prevalences were similar in all countries. OI prevalence remained high among ART-naïve patients in our cohort. The risks of TB, PCP, and cryptococcosis, but not CMV retinitis, differed between countries. Improved early HIV detection is warranted.
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http://dx.doi.org/10.4269/ajtmh.16-0783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508895PMC
July 2017

The effect of KIR2D-HLA-C receptor-ligand interactions on clinical outcome in a HIV-1 CRF01_AE-infected Thai population.

AIDS 2015 Aug;29(13):1607-15

aDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan bDepartment of Paediatrics, University of Oxford, Oxford, UK cThai National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi dDay Care Centre, Lampang Hospital, Lampang, Thailand eNagasaki University Global COE Program, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Objective: Class I human leukocyte antigen (HLA) alleles interact with both cytotoxic T lymphocytes through their T-cell receptors, and natural killer cells through their killer immunoglobulin-like receptors (KIRs). Compared with the reported protective effect of KIR3DL1/S1-HLA-Bw4 interactions in HIV-infected patients, the effect of KIR2D-HLA-C combinations on HIV control remains unclear. Here, we investigate the effect of KIR2D-HLA-C combinations on HIV disease progression.

Design: We performed a cross-sectional and longitudinal analysis of a Thai HIV cohort.

Methods: Two hundred and nine HIV-1 CRF01_AE-infected, treatment-naive Thai patients (CD4 T-cell counts of >200/μl) and 104 exposed seronegatives were studied. The effect of KIR-HLA receptor-ligand combinations on viral transmission and survival rate was statistically analyzed.

Results: We found the following results: higher frequency of patients expressing both KIR2DL3 and HLA-C1 among infected patients compared with exposed seronegative (odds ratio 4.8, P = 0.004), higher viral load in patients expressing HLA-C1 with KIR2DL3 compared with those without this receptor-ligand combination (median 4.8 vs. 4.2 log copies/ml, P = 0.033), higher numbers of KIR2DL3-HLA-C1 interactions was associated with a higher viral load (β = 0.13, P = 0.039 by linear regression model), and higher mortality rate in carriers of the KIR2DL3-HLA-C1 combination (adjusted hazard ratio 1.9, P = 0.012 by Cox hazard model).

Conclusion: We have identified a deleterious effect of the KIR2DL3-HLA-C1 receptor-ligand combination on HIV clinical outcomes in a Thai cohort. Further investigation into mechanisms underlying this susceptibility may aid the understanding of the role of natural killer cells in HIV disease control and pathogenesis.
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http://dx.doi.org/10.1097/QAD.0000000000000747DOI Listing
August 2015

Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.

BMC Infect Dis 2014 Oct 30;14:565. Epub 2014 Oct 30.

Food and Drug Administration, Ministry of Public Health, 88/7 Tiwanon road, Ampur Muang, Nonthaburi, 11000, Thailand.

Background: Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand.

Methods: All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models.

Results: Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification.

Conclusion: HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and lipodystrophy, respectively. Female gender, elder age, and having HLA-B*40:01 had protective effects on treatment failure-related regimen modification. This study provides further information of regimen modification for future tailored ART in Asia.
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http://dx.doi.org/10.1186/s12879-014-0565-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226857PMC
October 2014

HLA-B*35: 05 is a protective allele with a unique structure among HIV-1 CRF01_AE-infected Thais, in whom the B*57 frequency is low.

AIDS 2014 Apr;28(7):959-67

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto, Nagasaki City, Nagasaki, Japan.

Objective: To identify protective human leukocyte antigen (HLA) alleles in an HIV-infected south-east Asian population, in whom HLA-B*57 prevalence is lower than other ethnic groups, and HIV-1 CRF01_AE is the dominant circulating subtype.

Design: Cross-sectional study of Thai patients with chronic HIV infection.

Methods: Five hundred and fifty-seven HIV-1 CRF01_AE-infected Thais were recruited. Their HLA type and viral load were determined to statistically analyze the association of each allele in viral control. In-silico molecular dynamics was also used to evaluate the effect of HLA structure variants on epitope binding.

Results: HLA-B*35:05 was identified as the most protective allele (P=0.003, q=0.17), along with HLA-B*57:01 (P=0.044, q=0.31). Structurally, HLA-B*35:05 belonged to the HLA-B*35-PY group of HLA-B*35 alleles; however, unlike the other HLA-B*35 alleles that carry Arg (R) at residue 97, it has unique sequences at T94, L95, and S97, located within the peptide-binding groove. Analysis of the three-dimensional HLA structure and molecular dynamics indicates that S97 in HLA-B*35:05 leads to less flexibility in the groove, and shorter distances between the α-helixes compared with the disease-susceptible HLA-B*35-PY allele, HLA-B*35:01.

Conclusion: These data indicate the existence of a protective effect of HLA-B*57 across ethnic groups and highlight HLA-B*35:05 as an allele uniquely protective in subtype CRF01_AE-infected Thais. The divergence of HLA-B*35:05 from conventional HLA-B*35-PY structural sequences at the peptide-binding groove is consistent with previous studies that have identified HLA residue 97 as strongly influential in shaping HLA impact on immune control of HIV, and that a more restricted peptide-binding motif may be associated with improved control.
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http://dx.doi.org/10.1097/QAD.0000000000000206DOI Listing
April 2014

Efficacy and safety of topical Trikatu preparation in, relieving mosquito bite reactions: a randomized controlled trial.

Complement Ther Med 2014 Feb 1;22(1):34-9. Epub 2013 Sep 1.

The National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Introduction: Trikatu is composed of dried fruits of Piper nigrum L and Piper retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this preparation has been used to relieve pruritis, pain, and inflammation for a long time, there is no clinical evidence to confirm its efficacy and safety. Therefore, we performed a double-blind, within person-randomized controlled study of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on mosquito bite reactions.

Methods: All subjects were bitten by Aedes aegypti laboratory mosquitoes on their forearms and they were randomly assigned arms to apply either Trikatu or reference product on the mosquito bite papule. The main outcome was the difference of papule size reduction at 30 min, measured by a caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and patient satisfaction were assessed at 15, 30, 60, 180, and 360 min as secondary outcomes.

Results: There were no significant differences between treatment and reference arms on any outcome at any time of measurement.

Conclusion: Trikatu did not show additional effects for relieving mosquito bite reaction as compared with the reference product containing camphor, menthol, and eucalyptus. For further study, it is very important to consider a proper selection of subjects, comparator product, and concentration of extract when Trikatu preparation is investigated.
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http://dx.doi.org/10.1016/j.ctim.2013.08.014DOI Listing
February 2014

Changing burden of HIV/AIDS to clinical settings in Northern Thailand over 15 years.

Jpn J Infect Dis 2013 ;66(5):375-8

Day Care Center, Lampang Hospital.

We conducted a hospital-based descriptive study to describe the changing pattern of patient numbers, characteristics, and mortality rates among human immunodeficiency virus (HIV)-infected patients in northern Thailand over 15 years. The survival status on October 31, 2010 of all HIV-infected adults who attended an HIV center in a government hospital between 1995 and 2010 was ascertained. In total, 3,706 patients were registered, 2,118 (57.2%) of which were male. The survival status of 3,439 patients (92.9%) was available. In addition, 1,543 deaths were identified out of 12,858 person-year-observations (PYO) resulting in a mortality rate of 12.4 deaths/100 PYO (95% confidence interval [CI], 11.3-13.0). An initial decline in mortality rates was observed prior to 1999, probably because of an increase in the proportion of less symptomatic patients. After the introduction of the national highly active antiretroviral therapy (HAART) program, a profound decline in mortality rates was observed, reaching 2.0 deaths/100 PYO (95% CI, 1.4-2.9) in 2010. Simultaneously, the number of patients on follow-up increased by nearly fourfold. Although HAART has drastically improved the survival of HIV-infected patients, the number of patients receiving therapy at this HIV clinic has substantially increased. While referral of HIV patients to general physicians' care should be urged, we cannot overemphasize the importance of preventing new HIV infections.
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http://dx.doi.org/10.7883/yoken.66.375DOI Listing
March 2014

Impact of the National Access to Antiretroviral Program on the incidence of opportunistic infections in Thailand.

Int Health 2011 Jun;3(2):101-7

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Tiwanon Road, Nonthaburi 11000, Thailand.

The National Access to Antiretroviral Program caused a decline in HIV mortality in Thailand, but its impact on opportunistic infections (OI) remains unknown. The aim of this study was to compare the incidence of different OIs before and after the initiation of highly active antiretroviral therapy (HAART). Data from a prospective cohort at a hospital in northern Thailand were analysed. In total, 704 patients enrolled from July 2000 to October 2002 and not on HAART were followed up until October 2004. In addition, 409 patients who started HAART between April 2002 and January 2004 were followed up for 24 months. The impact of HAART on OIs was analysed using Cox proportional hazard models. HAART was associated with a strong reduction in OIs. The reduction appeared to vary by type: tuberculosis (TB), adjusted hazard ratio (AHR) = 0.2 (95% CI 0.1-0.5); pneumocystis pneumonia (PCP), AHR = 0.03 (95% CI 0.007-0.1); cryptococcal meningitis, AHR = 0.2 (95% CI 0.1-0.5); and penicilliosis, AHR = 0.1 (95% CI 0.06-0.3). In conclusion, HAART was very effective in reducing OIs, especially PCP. TB and cryptococcal meningitis remained frequent in the early phase of antiretroviral drug therapy. More attention to prophylaxis as well as earlier diagnosis and starting treatment for these OIs is recommended.
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http://dx.doi.org/10.1016/j.inhe.2010.12.004DOI Listing
June 2011

TIM1 haplotype may control the disease progression to AIDS in a HIV-1-infected female cohort in Thailand.

AIDS 2010 Jul;24(11):1625-31

National institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Objective: To investigate association of TIM1 sequence variations with HIV/AIDS progression.

Introduction: : HIV-1 infected individuals have wide variations in disease progression including AIDS. T cell immunoglobulin and mucin 1 (TIM1) is a cell surface protein involved in the regulation of Th1/Th2 immune response.

Materials And Methods: We sequenced the highly polymorphic exon 4 of TIM1 from 246 individuals of HIV-1 infected Thai female cohort to determine their TIM1 haplotypes. Associations of TIM1 haplotypes with baseline clinical data (sero-status, plasma viral load, CD4 cell count, and symptomatic AIDS) and survival status during 3 years of follow-up were evaluated.

Results: Seven TIM1 haplotypes, D3-A, D4, D3-C, D1, W-A, W-C, and D3-C*, were found in the cohort. Patients possessing the D3-A haplotype showed trends towards higher CD4 cell count (P = 0.06) and lower proportion of AIDS-related symptoms (P = 0.022) than the other patients at the baseline. Kaplan-Meier analysis demonstrated that patients carrying the D3-A haplotype had a better survival rates (P = 0.019) than the others. D3-A haplotypes was tightly linked to the lower expression levels of TIM1.

Conclusion: TIM1 D3-A haplotype is associated with the delay of disease progression to AIDS in the HIV-1 infected Thai females.
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http://dx.doi.org/10.1097/QAD.0b013e32833a8e6dDOI Listing
July 2010

Drug-resistant mutation patterns in CRF01_AE cases that failed d4T+3TC+nevirapine fixed-dosed, combination treatment: Follow-up study from the Lampang cohort.

Antiviral Res 2010 Jul 9;87(1):22-9. Epub 2010 Apr 9.

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

HIV/AIDS patients are treated in Thailand's national antiretroviral treatment (ART) program with a generic combination tablet of stavudine, lamivudine, and nevirapine (GPOvir). To determine GPOvir-resistant mutations, HIV-1 sequences of 59 GPOvir-failure cases from the Lampang cohort were compared with sequences from 76 randomly selected ART-naïve cases. The GPOvir-failure cases had not only known stavudine-, lamivudine- and nevirapine-resistant mutations, but also V118I, G196E, and H221Y. Among the 59 GPOvir-failure cases, 29 were ART-naïve prior to GPOvir (naïve group), and 30 had previous ART (exposed group). To clarify the effect of previous ART in drug-resistant acquisition pathways, naïve and exposed groups were compared. The exposed group had predominantly thymidine analogue-related mutations, whereas the naïve group had a higher prevalence of Q151M and K103N mutations. M184V lamivudine resistance was most frequent in both naïve and exposed groups. To identify which mutations in CRF01_AE pol were polymorphisms, the connection and RNase domains were also analyzed. CRF01_AE-specific polymorphisms were found in 19 residues, and GPOvir-failure cases had significantly higher frequency of N348I, E399D, P537S, and I542M. Our results expand identification of mutations in CRF01_AE pol that are polymorphisms by also analyzing the connection and RNase H domains.
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http://dx.doi.org/10.1016/j.antiviral.2010.04.001DOI Listing
July 2010

Demographic, socio-economic, behavioral and clinical factors predicting virologic failure with generic fixed-dose combination antiretroviral therapy before universal health insurance coverage in northern Thailand.

Southeast Asian J Trop Med Public Health 2009 Jan;40(1):71-82

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

We conducted a 2-year prospective cohort study to investigate multiple aspects of factors predicting the outcome of fixed-dose combination antiretroviral (ARV) therapy with lamivudine, stavudine, and nevirapine (GPOvir) at a government referral hospital in northern Thailand. At 6 and 24 months after the initiation of GPOvir, viral load (VL) was measured to determine virologic failure (>400 RNA copies/ml) and demographic, socio-economic, behavioral and clinical data were collected. From 10 April 2002 to 31 January 2004, 409 patients participated in this study: 64/364 (17.0%) at 6 months and 55/345 (15%) at 24 months virologically failed treatment. On univariate analysis, besides ARV experience [odds ratio (OR), 3.08, 95% confidence interval (CI), 1.71 -5.57] and the frequency of delayed doses (OR, 2.97; 95% CI, 1.47-6.00), we identified one socioeconomic factor significantly associated with virologic failure: "not having child" (OR, 1.85; 95% CI, 1.03 - 3.34). Although the association with "not having child" became marginal on multivariate analysis, results of in-depth interviews and group discussions indicated that having a child was a strong motivating factor for good treatment compliance. We suggest that patients without children may need more attention. Further investigation of socio-economic factors is warranted.
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January 2009

Substantially exposed but HIV-negative individuals are accumulated in HIV-serology-discordant couples diagnosed in a referral hospital in Thailand.

Jpn J Infect Dis 2009 Jan;62(1):32-6

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

The objectives of this study is to characterize HIV-serology-discordant couples diagnosed at a referral hospital in Thailand and to identify risk factors for HIV transmission among married couples. Firstly, cross-sectional analysis was conducted from July 2000 to October 2002. Out of 216 HIV-positive married men who knew the HIV status of their wives, the median number of sexual contacts in 63 men with HIV-negative wives was 6 times per month before the disclosure of HIV status, which did not differ from 153 men with HIV-positive wives. The majority of men with HIV-negative wives never used condoms. The median duration of marriage was 7 years for both groups. Unlike in previous reports, men with HIV-negative wives were significantly more symptomatic (P<0.01), and their CD4+ counts and viral loads did not differ from men with HIV-positive wives. Secondarily, 71 initially discordant couples were longitudinally followed until March 2005. Four were seroconverted out of 132.24 person-years of observation. In multivariate analysis incorporating sex, age, CD4+ count and sexual contact without a condom, shorter duration of marriage (<2 years) was found to be the only risk factor significantly associated with HIV transmission (hazard ratio of 15.2, P=0.04). Individuals substantially exposed to HIV but remaining HIV-negative are accumulated in discordant couples identified in a hospital, except in recently married couples.
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January 2009

Effects of CCR2 and CCRS polymorphisms on HIV-1 infection in Thai females.

J Acquir Immune Defic Syndr 2008 Mar;47(3):293-7

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Polymorphisms in CCR2 and CCR5 genes reportedly affect HIV-1 transmission and disease progression in HIV-1-infected individuals. In the study presented here, we examined the effects of CCR2 and CCR5 polymorphisms on HIV-1 transmission in 74 Thai females who were exposed to HIV but seronegative (ESN) and in 347 HIV-seropositive females. We found that the combination of 2 non-synonymous substitutions, CCR2 V64I and CCR5 G316A, tended to occur more frequently in ESN females (2 of 74) than in HIV-1 infected females (1 of 347) (P = 0.08). This suggested that non-synonymous substitution in the CCR5 gene also affects HIV-1 transmission in an Asian population in which the CCR5-Delta32 is very rare.
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http://dx.doi.org/10.1097/QAI.0b013e318162caabDOI Listing
March 2008

An efficient tool for surveying CRF01_AE HIV type 1 resistance in Thailand to combined stavudine-lamivudine-nevirapine treatment: mutagenically separated PCR targeting M184I/V.

AIDS Res Hum Retroviruses 2007 Dec;23(12):1461-8

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Under programs organized by the government of Thailand, HIV-1-infected patients have been treated since 2002 with several regimens, including a tablet known as GPOvir, which contains lamivudine, stavudine, and nevirapine. The aim of this study was to establish an effective assay, based on mutagenically separated PCR (MS-PCR), with the goal of surveying GPOvir-resistant HIV-1 cases. To determine the target mutation point for the assay, we analyzed the patterns of acquired drug resistance in plasma samples from GPOvir-failed cases. Of 428 HIV-1-infected individuals treated with GPOvir at Lampang Hospital in northern Thailand from 2002 to 2004, 66 had detectable viral loads after 3 months of treatment. The HIV-1 sequences of these 66 GPOvir-failed cases and 55 pre-GPOvir baseline samples were analyzed. The most prevalent drug resistance mutation among the samples was the lamivudine resistance M184I/V mutation. Based on this finding, we developed a new MS-PCR assay to detect the M184I/V mutation, and evaluated the assay performance for detecting GPOvir-resistant CRF01_AE cases. Comparing the results of M184I/V MS-PCR and sequence analyses, we found a concordance rate of 95% and an overall sensitivity of the M184I/V MS-PCR for detecting GPOvir-resistant cases of 79%. Considering the relatively low price of the assay, approximately $12.50 per sample, M184I/V MS-PCR may be a candidate for monitoring a large number of GPOvir-treated patients, particularly in developing nations.
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http://dx.doi.org/10.1089/aid.2007.0042DOI Listing
December 2007

The polymorphisms in DC-SIGNR affect susceptibility to HIV type 1 infection.

AIDS Res Hum Retroviruses 2007 May;23(5):686-92

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN) and its homologue DC-SIGNR (DC-SIGN related) have been thought to play an important role in establishing HIV infection by enhancing trans-infection of CD4(+)T cells in the regional lymph nodes. To identify polymorphisms associated with HIV-exposed seronegative (ESN) individuals in Thais, genomic DNA from 102 HIV-seronegative individuals of HIV-seropositive spouses, 305 HIV-seropositive individuals, and 290 HIV-seronegative blood donors was genotyped for two single nucleotide polymorphisms (SNPs) in DC-SIGN promoter (-139A/G and 336A/G), a repeat number of 69 bp in Exon 4 of DC-SIGN and DC-SIGNR, and one SNP in Exon 5 of DC-SIGNR (rs2277998A/G). We found that the proportion of individuals possessing a heterozygous 7/5 and 9/5 repeat and A allele at rs2277998 of DC-SIGNR in HIV-seronegative individuals of HIV-seropositive spouses was significantly higher than HIV-seropositive individuals [p = 0.0373, OR (95% CI) = 0.57 (0.32,1.01); p = 0.0232, OR (95% CI) = 0.38 (0.15,0.98); and p = 0.0445, OR (95% CI) = 0.61 (0.37,1.02), respectively]. Analysis after stratifying by gender showed that these associations were observed only in females but not in males. Moreover, HIV-seropositive females tend to have a homozygous 7/7 repeat more frequently than HIV-seronegative females with a marginal level of significance [p = 0.0556, OR (95% CI) = 1.79 (0.94,3.40)]. Haplotype analysis showed that the proportion of individuals possessing the 5A haplotype in HIV-seronegative females was significantly higher than HIV-seropositive females [p = 0.0133, OR = 0.50 (0.27,0.90)]. These associations suggest that DC-SIGNR may affect susceptibility to HIV infection by a mechanism that is different in females and males. Further studies are warranted to investigate the mechanisms of their function.
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http://dx.doi.org/10.1089/aid.2006.0212DOI Listing
May 2007

Protective effects of IL4-589T and RANTES-28G on HIV-1 disease progression in infected Thai females.

AIDS 2006 Jan;20(2):189-96

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Objective: To evaluate the effect of polymorphisms in interleukin-4 (IL4) and RANTES promoters on disease progression in HIV-1 infected Thais.

Design: Antiretroviral (ARV) drug-free HIV-1 infected females from the prospective cohort.

Methods: A total of 246 DNA samples were genotyped for IL4 and RANTES promoter polymorphisms by PCR-RFLP. Associations of genotype with HIV-1 disease progression were assessed with respect to baseline clinical data including plasma HIV-1 load, CD4 cell counts, and proportion of symptomatic/AIDS, and survival status during 3 years of follow-up.

Results: Patients with homozygous IL4-589T allele showed a significantly lower HIV-1 viral load (P = 0.005) and a higher CD4 cell count (P = 0.003) than the other patients with heterozygous IL4-589C/T or homozygous IL4-589C allele. Kaplan-Meier analysis demonstrated an apparent but insignificant trend towards better survival in homozygous IL4-589T patients. On the other hand, patients with RANTES-28G allele showed a significantly better survival while those with RANTES In1.1C allele without RANTES-28G showed a significantly poorer survival compared with those who did not possess either RANTES In1.1C or RANTES-28G (P = 0.02), although those polymorphisms only weakly associated with baseline viral load and CD4 cell counts.

Conclusions: Our results implicate the significant protective effect of IL4-589T and RANTES-28G on HIV disease progression in Thais. In contrast, RANTES In1.1C without RANTES-28G had an accelerating effect on HIV disease progression.
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http://dx.doi.org/10.1097/01.aids.0000199830.64735.6fDOI Listing
January 2006

Heterosexual transmission of novel CRF01_AE and subtype B recombinant forms of HIV type 1 in northern Thailand.

AIDS Res Hum Retroviruses 2005 Aug;21(8):734-8

Thai National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

The increased proportion of CRFO1_AE/subtype B recombinant infections among injecting drug users raised a concern that such recombinant forms may also spread in a heterosexual population in Thailand. Using the BootScan method, we reanalyzed pol gene sequences among 114 heterosexually infected individuals in northern Thailand, who were tested for a drug-resistance genotype between July 2000 and July 2001. Two individuals were suspected of carrying a recombinant HIV-1. Thus we analyzed a nearly full-length HIV genome in the two individuals and their spouses. An identical recombinant form of CRF01_AE and subtype B was found in one couple, indicating that this recombinant virus was heterosexually transmitted. Interestingly, this recombinant form had multiple breakpoints in the core protein of Gag and both infected individuals had a high CD4+ cell count without antiretroviral therapy. CRFO1/subtype B recombinant forms exist in a heterosexual population in northern Thailand. Some recombinant virus may be associated with a slow rate of HIV disease progression.
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http://dx.doi.org/10.1089/aid.2005.21.734DOI Listing
August 2005

Frequent detection of Epstein-Barr Virus and cytomegalovirus but not JC virus DNA in cerebrospinal fluid samples from human immunodeficiency virus-infected patients in northern Thailand.

J Clin Microbiol 2005 Jul;43(7):3484-6

National Institute of Health, Department of Medical Sciences, Nonthaburi, Thailand.

Applying nested-PCRs, we frequently detected DNA of Epstein-Barr virus and cytomegalovirus but not JC virus in cerebrospinal fluid samples from 140 human immunodeficiency virus-infected patients with central nervous system symptoms in northern Thailand. Despite the low incidence of primary central nervous system lymphoma or cytomegalovirus encephalitis among Thai AIDS patients, Epstein-Barr virus and cytomegalovirus infections in the central nervous system are common.
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http://dx.doi.org/10.1128/JCM.43.7.3484-3486.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169133PMC
July 2005

Mortality analysis of HIV-1 infected patients for prioritizing antiretroviral drug therapy.

J Med Assoc Thai 2004 Aug;87(8):951-4

Lampang Hospital, Ampur Muang Lampang, Thailand.

Mortality data of patients, classified according to their clinical status and CD4+ cell count status, would be very useful to guide clinicians to prioritizing patients who need antiretroviral drug therapy. In the current study, the authors re-analyzed data derived from a previously published retrospective study of HIV-1-infected individuals at Lampang Hospital in northern Thailand. According to the Cox proportional hazard model, compared to asymptomatic patients with a high CD4+ cell count (> 200 cell/microl), the mortality rate of asymptomatic patients with a medium CD4+ cell count (100-199 cell/microl) did not significantly differ. However, the mortality rate of patients with a CD4+ cell count below 100 cell/microl was at least 16 times higher, regardless of the presence of clinical symptoms. Based on these results, the authors produced a Lampang Hospital guideline of antiretroviral drug use; priority of antiretroviral therapy should, therefore, be given to patients with CD4+ cell count < 100 cell/microl.
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August 2004

Study of antiretroviral drug-resistant HIV-1 genotypes in northern Thailand: role of mutagenically separated polymerase chain reaction as a tool for monitoring zidovudine-resistant HIV-1 in resource-limited settings.

J Acquir Immune Defic Syndr 2004 Aug;36(5):1051-6

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

As the number of HIV-1-infected individuals receiving antiretroviral drugs has been rapidly increasing in developing countries, there is an urgent need for drug resistance genotype information of non-B subtype HIV-1 and for the establishment of a practical system of monitoring drug-resistant viruses. This study first sequenced the reverse transcriptase region of HIV-1 in 112 infected individuals who had been treated with zidovudine (AZT)/didanosine or AZT/zalcitabine as dual therapy at a government hospital in northern Thailand and then compared the above sequence method with mutagenically separated polymerase chain reaction (MS-PCR) for detecting M41L and K70R mutations. Concordant rates of detecting M41L and K70R mutations by the 2 methods were 96.9% (93/96) and 92.7% (89/96), respectively. The M41L and K70R MS-PCR could detect 86.4% of AZT-resistant strains with any resistance mutation, which was determined by the sequencing method. Then 292 drug-naive individuals were screened for the presence of drug-resistant HIV-1 by the MS-PCR assay and it was found that 2 individuals (0.7%) carried viruses with either the M41L or K70R mutation. It is feasible to test a large number of samples with MS-PCR, which is sensitive, cheap, and easy to perform and does not require sophisticated equipment. The M41L and K70R MS-PCR is potentially a useful tool to monitor the spread of AZT-resistant HIV-1 in resource-limited countries.
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http://dx.doi.org/10.1097/00126334-200408150-00008DOI Listing
August 2004

HIV infection and risk factors among Bangkok prisoners, Thailand: a prospective cohort study.

BMC Infect Dis 2003 Oct 28;3:25. Epub 2003 Oct 28.

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi Thailand.

Background: Incarceration has been associated with HIV infection among injection drug users. However, data on HIV risk factors of the inmates during incarceration are rarely reported from Thailand.

Methods: A prospective cohort of 689 male inmates in a Bangkok central prison was studied during 2001-2002. Follow up visits were conducted for 5 months, with testing for HIV and other infections and interviewing of demographics and risk behaviors.

Results: Among 689 male inmates, half (50.9 %) were drug injectors. About 49% of the injectors had injection during incarceration. Most (94.9%) of the injectors had shared injection paraphernalia with others. Successful follow up rate was 98.7% after 2,581 person-months observation. HIV incidence was 4.18 per 100 person--years among all inmates, and 11.10 per 100 person--years among the injection inmates. Multivariate analysis identified variables associated with HIV prevalence: history of injection [OR = 2.30, 95%CI: 1.91-2.77], positive urine opiate test [OR = 5.04, 95%CI: 2.63-9.67], history of attendance to drug withdrawal clinics [OR = 2.00, 95%CI: 1.19-3.35] and presence of tattoos on the body [OR = 1.23, 95%CI: 1.01-1.52].

Conclusions: The main HIV risk factors of Bangkok inmates were those related to drug injection. Harm reduction measures and HIV intervention strategies should be implemented to prevent more spread of HIV among the inmates and into the community.
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http://dx.doi.org/10.1186/1471-2334-3-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC270083PMC
October 2003

Survival benefit from non-highly active antiretroviral therapy in a resource-constrained setting.

J Acquir Immune Defic Syndr 2003 Feb;32(2):157-60

Day Care Center, Lampang Hospital, Lampang, Thailand.

Mortality rates among HIV-1-infected patients attending a government hospital in northern Thailand were investigated to evaluate the effect of antiretroviral (ARV) drug therapy on mortality. Demographic, clinical, and laboratory data and history of ARV drug therapy were collected from all HIV-1-infected adult patients who attended the Day Care Center clinic from October 2, 1995 through October 31, 1999. The survival status of patients until October 31, 1999 was ascertained from the hospital records, mailing letters, and death certificates at the Provincial Health Office. Of 1110 patients who attended the clinic, we had data on duration of follow-up for 1081 (97%) with a total of 1175 person-years of observation; 607 (54.7%) patients died. Clinical status, CD4 group, ARV drug group, and registered year were independently associated with death. The adjusted hazard ratio of monotherapy to no therapy was 0.65 (95% CI: 0.48, 0.87; p = .001) and that of dual therapy was 0.43 (95% CI: 0.29, 0.62; p < .001). The mortality rate of patients attending a government hospital in northern Thailand is high. Suboptimum ARV drug regimens like dual therapy had a substantial survival benefit. Further cost reduction for multiple ARV drug regimens is impatiently awaited.
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http://dx.doi.org/10.1097/00126334-200302010-00007DOI Listing
February 2003

Impact of HIV vaccination on laboratory diagnosis: case reports.

BMC Infect Dis 2002 Sep 10;2:19. Epub 2002 Sep 10.

National Institute of Health, Department of Medical Science, Ministry of Public Health, Thailand.

Background: It has not been clearly demonstrated whether HIV vaccination can complicate routine HIV testing. In this report, we describe the laboratory data of two prisoners who received rgp120 vaccine in a phase III trial underway in Thailand. These data indicate that previous vaccination may complicate the interpretation of screening HIV diagnostic tests.

Case Presentation: The participants were identified from a cohort study on "Health factors related to HIV-1 and other viral infections among incarcerated people" that was approved by The Ethical Committee for Research in Human Subjects, Ministry of Public Health, Thailand. HIV diagnosis was definitively established with serial specimens using multi-screening tests, Western blot and diagnostic PCR.Anti-HIV screening tests consistently exhibited either weakly reactive or inconclusive results. The band patterns of the Western blot analysis corresponded to those found in individuals who received the rgp120 vaccination. Definite results were established using diagnostic PCR, which exhibited consistently negative results with follow-up specimens. Such problems in HIV testing are not easily resolved in the routine clinical setting in Thailand.

Conclusions: These data demonstrate that HIV-1 vaccination interferes with routine diagnostic tests. Similar cases will not be uncommon in Thailand, where 2,545 people have already participated in a phase III trial.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC126272PMC
http://dx.doi.org/10.1186/1471-2334-2-19DOI Listing
September 2002