Publications by authors named "Panita Pathipvanich"

35 Publications

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

Evaluation of HIV-1 neutralizing and binding antibodies in maternal-infant transmission in Thailand.

Virology 2020 09 24;548:152-159. Epub 2020 Jun 24.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA. Electronic address:

Despite anti-retroviral therapy (ART) interventions for HIV+ pregnant mothers, over 43,000 perinatal infections occur yearly. Understanding risk factors that lead to mother-to-child transmission (MTCT) of HIV are critical. We evaluated maternal and infant plasma binding and neutralizing antibody responses in a drug-naïve, CRF01_AE infected MTCT cohort from Thailand to determine associations with transmission risk. Env V3-specific IgG and neutralizing antibody responses were significantly higher in HIV- infants, as compared to HIV+ infants. In fact, infant plasma neutralizing antibodies significantly associated with non-transmission. Conversely, increased maternal Env V3-specific IgG and neutralizing antibody responses were significantly associated with increased transmission risk, after controlling for maternal viral load. Our results highlight the importance of evaluating both maternal and infant humoral immune responses to better understand mechanisms of protection, as selective placental antibody transport may have a role in MTCT. This study further emphasizes the complex role of Env-specific antibodies in MTCT of CRF01_AE HIV.
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http://dx.doi.org/10.1016/j.virol.2020.05.007DOI Listing
September 2020

Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors.

J Infect 2019 11 8;79(5):454-461. Epub 2019 Aug 8.

Institut de Recherche pour le Développement (IRD) Unit 174-PHPT, Kaew Nawarat Rd, Tambon Wat Ket, Amphoe Mueang Chiang Mai, Chiang Mai, Thailand; Harvard T.H. Chan School of Public Health, Boston, MA, USA; Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand. Electronic address:

Objectives: The risk of kidney dysfunction on the WHO recommended first line regimens containing tenofovir disoproxil fumarate (TDF) without protease inhibitors (PI) remains unclear in Asian patients, especially those with low body weight.

Methods: Using data collected in a multicenter clinical trial in Thailand and proportional hazard regression models, we compared the risk of a >25% estimated glomerular filtration rate (eGFR) reduction in HIV naïve patients initiating TDF or zidovudine (AZT) containing non-PI regimen.

Results: Of 640 patients included in the analysis, 461 (72%) received a TDF-containing regimen for a median 6.7 years and 179 (28%) an AZT-containing regimen for 6.5 years. The risk of a >25% eGFR reduction was not associated with treatment (HR 1.11, 95% CI 0.84-1.47, P = 0.46). In multivariate analysis, the risk of >25% eGFR reduction form baseline was associated with body weight at baseline (HR 2.12, 95% CI 1.48-3.02 for <48 kg patients and HR 1.64, 95% CI 1.20-2.25 for 48-59.9 kg patients, compared to those with >60 kg, P < 0.001) and hypertension (HR 4.03, 95% CI 2.0-8.0, P < 0.001). The effect of baseline weight on >25% eGFR reduction did not significantly vary with treatment (P = 0.27).

Conclusions: The risk of eGFR reduction was not higher on TDF- versus AZT-based non-PI regimens. Although the risk of eGFR reduction was greater for patients of lower body weight, this risk was not significantly increased by TDF.
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http://dx.doi.org/10.1016/j.jinf.2019.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825894PMC
November 2019

Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors.

J Infect 2019 11 8;79(5):454-461. Epub 2019 Aug 8.

Institut de Recherche pour le Développement (IRD) Unit 174-PHPT, Kaew Nawarat Rd, Tambon Wat Ket, Amphoe Mueang Chiang Mai, Chiang Mai, Thailand; Harvard T.H. Chan School of Public Health, Boston, MA, USA; Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand. Electronic address:

Objectives: The risk of kidney dysfunction on the WHO recommended first line regimens containing tenofovir disoproxil fumarate (TDF) without protease inhibitors (PI) remains unclear in Asian patients, especially those with low body weight.

Methods: Using data collected in a multicenter clinical trial in Thailand and proportional hazard regression models, we compared the risk of a >25% estimated glomerular filtration rate (eGFR) reduction in HIV naïve patients initiating TDF or zidovudine (AZT) containing non-PI regimen.

Results: Of 640 patients included in the analysis, 461 (72%) received a TDF-containing regimen for a median 6.7 years and 179 (28%) an AZT-containing regimen for 6.5 years. The risk of a >25% eGFR reduction was not associated with treatment (HR 1.11, 95% CI 0.84-1.47, P = 0.46). In multivariate analysis, the risk of >25% eGFR reduction form baseline was associated with body weight at baseline (HR 2.12, 95% CI 1.48-3.02 for <48 kg patients and HR 1.64, 95% CI 1.20-2.25 for 48-59.9 kg patients, compared to those with >60 kg, P < 0.001) and hypertension (HR 4.03, 95% CI 2.0-8.0, P < 0.001). The effect of baseline weight on >25% eGFR reduction did not significantly vary with treatment (P = 0.27).

Conclusions: The risk of eGFR reduction was not higher on TDF- versus AZT-based non-PI regimens. Although the risk of eGFR reduction was greater for patients of lower body weight, this risk was not significantly increased by TDF.
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http://dx.doi.org/10.1016/j.jinf.2019.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825894PMC
November 2019

High subsequent and recurrent sexually transmitted infection prevalence among newly diagnosed HIV-positive Thai men who have sex with men and transgender women in the Test and Treat cohort.

Int J STD AIDS 2019 02 9;30(2):140-146. Epub 2018 Oct 9.

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

We determined subsequent and recurrent sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women (TGW) in the Test and Treat cohort. Thai MSM and TGW adults with previously unknown HIV status were enrolled and tested for HIV. Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and syphilis were tested at baseline, month 12, and month 24 to identify subsequent STIs (any STIs diagnosed after baseline) and recurrent STIs (any subsequent STIs diagnosed among those with positive baseline STIs). Among 448 participants, 17.8% were HIV-positive, the prevalence of subsequent STIs and recurrent STIs was 42% (HIV-positive versus HIV-negative: 66.3% versus 36.7%, p < 0.001) and 62.3% (81% versus 52.5%, p < 0.001), respectively. Common subsequent STIs by anatomical site were rectal CT infection (21.7%), rectal NG infection (13.8%), pharyngeal NG infection (13.1%), and syphilis (11.9%). HIV-positive status was associated with both subsequent STIs (adjusted hazard ratio [aHR] 2.38; 95%CI 1.64-3.45, p < 0.001) and recurrent STIs (aHR 1.83; 95%CI 1.16-2.87, p = 0.01). The results show that newly diagnosed HIV-positive MSM and TGW were at increased risk of STIs despite being in the healthcare system. STI educational counseling is necessary to improve STI outcomes among MSM and TGW in both HIV prevention and treatment programs.
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http://dx.doi.org/10.1177/0956462418799213DOI Listing
February 2019

Sexually transmitted infections and HIV RNA levels in blood and anogenital compartments among Thai men who have sex with men before and after antiretroviral therapy: implication for Treatment as Prevention programme.

J Int AIDS Soc 2018 09;21(9):e25186

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

Introduction: Sexually transmitted infections (STIs) are common among HIV-positive men who have sex with men (MSM). There have been concerns that undiagnosed and untreated STIs could undermine efforts to use antiretroviral therapy (ART) for prevention due to genital secretion infectiousness. We evaluated the correlation between STIs and HIV RNA in anogenital compartments among HIV-positive MSM before and after ART.

Methods: MSM participants newly diagnosed with HIV were offered ART regardless of CD4 count during November 2012 to November 2015. Syphilis serology, oropharyngeal swab, rectal swab, urine collection for gonorrhoea and chlamydia nucleic acid amplification testing, and HIV RNA measurement in blood, semen and rectal samples were performed at baseline, 12 and 24 months thereafter.

Results: Of 143 HIV-positive MSM, 16.1% had syphilis, 23.1% had gonorrhoea and 32.8% had chlamydia at baseline. Participants with STIs at baseline had higher median HIV RNA levels in blood plasma (p = 0.053), seminal plasma (p = 0.01) and rectal secretions (p = 0.002) than those without STIs. Multivariate models identified HIV RNA 100,000 to 500,000 (OR 6.74, 95% CI 2.24 to 20.28, p = 0.001) and >500,000 (OR 9.39, 95% CI 1.08 to 81.72, p = 0.04) copies/mL in blood, CD4 count <350 cells/mm (OR 4.20, 95% CI 1.05 to 16.70, p = 0.04) and having any STIs (OR 2.62, 95% CI 1.01 to 6.80 p = 0.047) to be associated with detectable (>40 copies/mL) seminal plasma HIV RNA. Having chlamydia at any sites (OR 3.17, 95% CI 1.07 to 9.44, p = 0.04) was associated with detectable rectal HIV RNA. Incidences of syphilis, gonorrhoea and chlamydia were 13.4, 16.4 and 18.1 per 100 person-years respectively. Nine participants had detectable HIV RNA (five in blood, one in semen, two in rectal samples and one in both blood and rectal samples) at 12 and/or 24 months after ART.

Conclusions: STIs were extremely common among HIV-positive MSM prior to and after ART. ART effectively reduced HIV RNA in all compartments. The correlation between STIs and anogenital HIV RNA, especially prior to ART and likely until complete HIV RNA suppression from ART is achieved, points to the importance of integrating asymptomatic STIs screening into Treatment as Prevention programme for MSM.
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http://dx.doi.org/10.1002/jia2.25186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141901PMC
September 2018

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

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

Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

PLoS Med 2013 Aug 6;10(8):e1001494. Epub 2013 Aug 6.

Unité Mixte Internationale 174, Institut de Recherche pour le Développement (IRD)-Programs for HIV Prevention and Treatment (PHPT), Chiang Mai, Thailand.

Background: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.

Methods And Findings: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm(3). The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p=0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p=0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.

Conclusions: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.

Trial Registration: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.
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http://dx.doi.org/10.1371/journal.pmed.1001494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735458PMC
August 2013

The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection.

PLoS One 2012 27;7(7):e41696. Epub 2012 Jul 27.

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

Introduction: The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating.

Materials And Methods: 14 peptides based on consensus HIV-1 CRF01_AE amino acid sequences were designed for use in IFN-γ ELISpot assays and (51)Cr release assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico epitope-HLA prediction was performed.

Results: 29/66 (43.9%) patients recognized at least one peptide. In total 79 responses were seen against all 14 peptides. 28/79 (35.4%) of the responses were in patients with HLA alleles previously reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in individuals with HLA alleles previously reported to restrict epitopes of HIV clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not associated with HLA alleles previously known to restrict HIV epitopes. In silico epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%) were associated with HLA-C alleles. We further confirmed a novel HLA restriction of a previously identified HIV-1 Gag epitope [p24(122-130): PPIPVGDIY (PY9)] by HLA-B*40:01 with a standard (51)Cr release assay.

Discussion: CTL recognition sites in HIV-1 Gag were similar among different clades but the HLA restriction differed in Thai patients. This disparity in HLA restriction along different populations illustrated the importance of clade- and population-specific HLA analysis prior to CTL vaccine design.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0041696PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407236PMC
April 2013

Screening scheme development for active TB prediction among HIV-infected patients.

Southeast Asian J Trop Med Public Health 2011 Jul;42(4):867-75

Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

The objective of this study was to develop and evaluate a simple scoring scheme to screen for active tuberculosis (TB) among HIV-infected patients. Two hundred fifty-seven HIV-infected patients were enrolled in the study between April 2009 and May 2010 from Mae Sai District Hospital and Lampang Regional Hospital. Participants underwent routine evaluations to diagnose TB. Data collection included demographics, medical history, signs and symptoms and laboratory results. Of the 257 HIV-infected patients enrolled, 66 (25.7%) were diagnosed with active TB. Six variables were statistically significant predictors of active TB (p < 0.05): BMI < or = 19 kg/m2, cough > 2 weeks, shaking chills > or = 1 week not taking antiretroviral drugs, a CD4+ cell count level < 200 cells/microl, and had a history of TB. A risk score (ranging from 0 to 16) gave a 92.1% sensitivity of being associated with active TB. A low risk score (< or = 2.0), a moderate risk score (3.0-7.0), and a high risk score (>7.0) gave positive likelihood ratios (LHR+) of 0.04 (95% CI 0.01-0.24), 2.56 (95% CI 1.71-3.85), and 11.72 (95% CI 4.91-27.96), respectively. This screening tool may be useful to identify patients who should have further diagnostic testing for TB, but requires further validation before adoption due to the variability of predicting factors and the prevalence of TB in the target population.
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July 2011

Diagnostic value of two rapid immunochromatographic tests for suspected tuberculosis diagnosis in clinical practice.

J Med Assoc Thai 2011 Oct;94(10):1198-204

Clinical Epidemiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Objective: To evaluate and compare the diagnostic value of two immunochromatographic tests for tuberculosis (ICT-TB) in clinical practice.

Material And Method: The present extended cross-sectional study investigated suspected active TB patients at Maesai district hospital, and Lampang regional hospital between April 2009 and May 2010. Subjects underwent two commercial ICT-TB serum tests including: an endogenous ICT-TB, a local made test coated with 38 kD, 16 kD, and 6 kD antigens; and an exogenous ICT-TB, an imported test coated with 38 kD and lipoarabinomanan [LAM] antigens. All subjects received two months of follow up.

Results: Of 401 patients, 146 (36.4%) had active TB, and 206 (51.4%) were HIVseropositive. An endogenous ICT-TB was superior to an exogenous ICT-TB in all diagnostic values measured except for specificity. In all patients, sensitivity was low, 35.6% (95% CI: 30.9-40.3) in an endogenous ICT-TB vs. 13.7% (95% CI: 10.3-17.1) in an exogenous ICT-TB. The specificity was high and equivalent in both tests, 93.7% (95%CI: 91.4-96.1). Higher diagnostic values were found among human immunodeficiency virus (HIV) seronegatives than in HIV seropositives when unadjusted for CD4+ cell count level. The likelihood ratios (LHR) were higher in patients with CD4+ cell count over 200 cells/microL than for the HIV seronegative group (LHR+ 7.6 vs. 4.8 in an endogenous ICT-TB, and 2.5 vs. 1.9 in an exogenous ICT-TB).

Conclusion: For the present study setting, an endogenous ICT-TB can be a meaningful tool for first-line testing to rule in TB suspected cases. Subgroups of HIV seronegative and HIV seropositive patients with CD4+ cell count over 200 cells/microL may be expected to benefit most from the test.
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October 2011

Diagnostic value of an immunochromatographic test over clinical predictors for tuberculosis in HIV patients.

Clin Epidemiol 2011 12;3:237-44. Epub 2011 Sep 12.

Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand;

Purpose: The value of an immunochromatographic test for tuberculosis (ICT-TB) combined with clinical predictors has yet to be evaluated in Thailand. This study aimed to assess any additional diagnostic value of an ICT-TB test over that of clinical predictors in a group of human immunodeficiency virus (HIV) patients as well as in subgroups of HIV patients classified by clinical risk scores.

Patients And Methods: An extended cross-sectional study was conducted at a community hospital in Chiang Rai and a general hospital in Lampang. HIV patients registered between April 2009 and May 2010 were screened by a locally made ICT-TB test, including 38, 16, and 6 kD Microbacterium tuberculosis antigens, as well as by routine evaluations for TB diagnosis. Demographic data, medical history, signs, and symptoms were recorded. Participants were followed up for 2 months for final ascertainment of TB diagnosis.

Results: Of 206 patients, 37 (18%) had TB. Four clinical predictors were identified: low body mass index (<19 kg/m(2)), prolonged cough (duration >2 weeks), shaking chills (≥1 week), and no use of antiretrovirals. The area under the receiver operating curve was 90.2%; adding the ICT-TB test result increased the area nonsignificantly to 91.6% (P = 0.40). When patients were categorized by risk scores derived from selected clinical predictors into low (scores ≤7) and high (scores >7) TB risk groups, a positive ICT-TB test increased the positive predictive value nonsignificantly in the low risk group (from 12.5% to 27.3%, P = 0.17) and the high risk group (from 78.6% to 80.8%, P = 0.73).

Conclusion: In this study setting, the ICT-TB test did not enhance TB diagnosis over the four clinical predictors in the overall group or any subgroups of HIV patients classified by clinical risk scores.
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http://dx.doi.org/10.2147/CLEP.S24668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191113PMC
November 2011

Unique CRF01_AE Gag CTL epitopes associated with lower HIV-viral load and delayed disease progression in a cohort of HIV-infected Thais.

PLoS One 2011 3;6(8):e22680. Epub 2011 Aug 3.

Department of Clinical Medicine, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.

Cytotoxic T Lymphocytes (CTLs) play a central role in controlling HIV-replication. Although numerous CTL epitopes have been described, most are in subtype B or C infection. Little is known about CTL responses in CRF01_AE infection. Gag CTL responses were investigated in a cohort of 137 treatment-naïve HIV-1 infected Thai patients with high CD4+ T cell counts, using gIFN Enzyme-Linked Immunospot (ELISpot) assays with 15-mer overlapping peptides (OLPs) derived from locally dominant CRF01_AE Gag sequences. 44 OLPs were recognized in 112 (81.8%) individuals. Both the breadth and magnitude of the CTL response, particularly against the p24 region, positively correlated with CD4+ T cell count and inversely correlated with HIV viral load. The breadth of OLP response was also associated with slower progression to antiretroviral therapy initiation. Statistical analysis and single peptide ELISpot assay identified at least 17 significant associations between reactive OLP and HLA in 12 OLP regions; 6 OLP-HLA associations (35.3%) were not compatible with previously reported CTL epitopes, suggesting that these contained new CTL Gag epitopes. A substantial proportion of CTL epitopes in CRF01_AE infection differ from subtype B or C. However, the pattern of protective CTL responses is similar; Gag CTL responses, particularly against p24, control viral replication and slow clinical progression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022680PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149616PMC
December 2011

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

HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals and its association with plasma viral load.

PLoS One 2010 Jun 17;5(6):e11179. Epub 2010 Jun 17.

Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Background: The human leukocyte antigen (HLA)-restricted cytotoxic T-lymphocyte (CTL) immune response is one of the major factors determining the genetic diversity of human immunodeficiency virus (HIV). There are few population-based analyses of the amino acid variations associated with the host HLA type and their clinical relevance for the Asian population. Here, we identified HLA-associated polymorphisms in the HIV-1 CRF01_AE Gag protein in infected married couples, and examined the consequences of these HLA-selected mutations after transmission to HLA-unmatched recipients.

Methodology/principal Findings: One hundred sixteen HIV-1-infected couples were recruited at a government hospital in northern Thailand. The 1.7-kb gag gene was amplified and directly sequenced. We identified 56 associations between amino acid variations in Gag and HLA alleles. Of those amino acid variations, 35 (62.5%) were located within or adjacent to regions reported to be HIV-specific CTL epitopes restricted by the relevant HLA. Interestingly, a significant number of HLA-associated amino acid variations appear to be unique to the CRF01_AE-infected Thai population. Variations in the capsid protein (p24) had the strongest associations with the viral load and CD4 cell count. The mutation and reversion rates after transmission to a host with a different HLA environment varied considerably. The p24 T242N variant escape from B57/58 CTL had a significant impact on the HIV-1 viral load of CRF01_AE-infected patients.

Conclusions/significance: HLA-associated amino acid mutations and the CTL selection pressures on the p24 antigen appear to have the most significant impact on HIV replication in a CRF01_AE-infected Asian population. HLA-associated mutations with a low reversion rate accumulated as a footprint in this Thai population. The novel HLA-associated mutations identified in this study encourage us to acquire more extensive information about the viral dynamics of HLA-associated amino acid polymorphisms in a given population as effective CTL vaccine targets.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011179PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887364PMC
June 2010

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

Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure.

Clin Infect Dis 2010 May;50(10):1397-404

Institut de Recherche pour le Développement, UMI 174-PHPT, Thailand.

Background: Antiretroviral therapy (ART) has become more available throughout the developing world during the past 5 years. The World Health Organization recommends nonnucleoside reverse-transcriptase inhibitor-based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of human immunodeficiency virus (HIV)-1. There is no simple and efficient method to detect such mutations at the initiation of ART.

Methods: One hundred eighty-one women who were participating in a clinical trial to prevent mother-to-child transmission and who started NVP-ART after they had received sdNVP or a placebo were included in the study. One hundred copies of each patient's HIV-1 DNA were tested for NVP-resistance point-mutations (K103N, Y181C, and G190A) with a sensitive oligonucleotide ligation assay that was able to detect mutants even at low concentrations (> or = 5% of the viral population). Virologic failure was defined as confirmed plasma HIV-1 RNA >50 copies/mL after 6 to 18 months of NVP-ART.

Results: At initiation of NVP-ART, resistance mutations were identified in 38 (26%) of 148 participants given sdNVP (K103N in 19 [13%], Y181C in 8 [5%], G190A in 28 [19%], and > or = 2 mutations in 15 [10%]), at a median 9.3 months after receipt of sdNVP. The risk of virologic failure was 0.62 (95% confidence interval [CI], 0.46-0.77) in women with > or = 1% resistance mutation, compared with a risk of 0.25 (95% CI, 0.17-0.35) in those without detectable resistance mutations (P < .001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load higher than the median at NVP-ART initiation.

Conclusions: Access to simple and inexpensive assays to detect low concentrations of NVP-resistant HIV-1 DNA before the initiation of ART could help improve the outcome of first-line ART.
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http://dx.doi.org/10.1086/652148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856716PMC
May 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

Mycobacterium avium and Burkholderia pseudomallei (Melioidosis) coinfection in an HIV-positive patient.

Asian Pac J Allergy Immunol 2006 Dec;24(4):239-43

JICA-NIH Project, Ministry of Public Health, Thailand.

A 29 year old HIV positive Thai female with CD4 count of 10 cells/mm3 presented with chronic diffuse abdominal pain, fever, weight loss, anemia and leucopenia. Ultrasonography demonstrated diffuse upper abdominal lymphadenopathy with ascites. Microbiological and molecular work up of the specimen obtained by ultrasound-guided lymph node aspiration revealed co-infection with Burkholderia pseudomallei and Mycobacterium avium. Indirect hemagglutination, IgM-indirect fluorescent antibody, and IgG-indirect fluorescent antibody to Burkholderia pseudomallei were < 1:20, < 1:50 and < 1:50, respectively, at nine months, four months before the culture diagnosis and two months, eight months after the culture diagnosis of Burkholderia pseudomallei infection. The patient was treated initially with two weeks of intravenous ceftazidime, followed by oral cotrimoxazole, doxycycline and chloramphenicol. Clarithromycin and ofloxacin were added after the identification of Mycobacterium avium and its susceptibility test. The patients demonstrated clinical improvement with decreasing abdominal pain and resolution of fever.
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December 2006

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