Publications (6) View all
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Article: Vitamin D Insufficiency and Deficiency among HIV-1-Infected Patients in a Tropical Setting.
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ABSTRACT: Vitamin D plays role in bone health and the regulation of the immune system. A cross-sectional study of serum 25-hydroxyvitamin D (25[OH]D) levels was conducted among HIV-1-infected Thai patients to determine the prevalence and associated factors of low vitamin D levels (25[OH]D <30 ng/mL) in tropical setting. 25-Hydroxyvitamin D was measured by liquid chromatography/tandem mass spectrometry. Of 178 patients, 58% received antiretroviral therapy at median (interquartile range [IQR]) duration of 7.4 (5.9-8.5) years. The prevalence of 25(OH)D deficiency (<20 ng/mL) and insufficiency (20-29.9 ng/mL) was 26.8% and 44.9%, respectively. Multivariate analysis showed that receiving efavirenz (EFV) was significantly associated with low vitamin D status (odds ratio = 3.60; 95% confidence interval, 1.06-12.15, P <.05). The mean (±standard deviation) level of 25(OH)D in patients receiving and not receiving EFV was 22.9 (6.6) and 28.6 (10.7) ng/mL, respectively, (P <.05). Low vitamin D status is common and needs to be assessed among HIV-infected patients including tropical residents especially when EFV is used.Journal of the International Association of Physicians in AIDS Care (JIAPAC) 01/2012; 11(5):305-10. -
Article: Genome-wide association study identifies variations in 6p21.3 associated with nevirapine-induced rash.
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ABSTRACT: We aimed to identify disease-predisposing variations with nevirapine-induced rash using genome-wide single-nucleotide polymorphisms (SNPs) as genetic markers. A genome-wide association study (GWAS) was performed using ∼550000 markers in 72 human immunodeficiency virus (HIV)-infected Thai patients with nevirapine-induced rash and 77 nevirapine-tolerant patients, and then candidate SNPs were further evaluated in a replication set (88 patients with nevirapine-induced rash and 145 nevirapine-tolerant patients). The genome-wide association analysis and replication studies of candidate SNPs identified significant associations of nevirapine-induced rash with 2 SNPs (rs1265112 and rs746647) within CCHCR1 on chromosome 6p21.3 (P(GWAS) = 1.6 × 10(-4); P(replication) = 2.6 × 10(-5); P(combined) = 1.2 × 10(-8)). The odds ratio (OR) of the risk genotypes under a dominant model was 4.36 (95% confidence interval [CI], 2.58-7.36). The noncoding SNPs rs1265112 and rs746647 were in complete linkage disequilibrium with the nonsynonymous SNP rs1576 (r(2) = 1.00), which has been associated with psoriasis. The logistic regression analysis also indicated genetic variations in CCHCR1 to be significantly associated with rash, with an OR of 2.59 (95% CI, 1.82-3.68; P = .007). The receiver operating characteristic curve showed that the algorithm had an area under the curve of 76.4%, which was developed with 5 factors: rs1576*G status, HLA-B*3505 status, not receiving prescribed lead-in of nevirapine, history of drug allergy, and CD4 cell count prior to the nevirapine treatment. We demonstrated that genetic variations in CCHCR1 are strongly associated with nevirapine-induced rash. A predictive model that includes genetic and clinical risk factors for nevirapine-associated rash might be useful in lowering the incidence of rash associated with nevirapine initiation among HIV-infected patients.Clinical Infectious Diseases 08/2011; 53(4):341-8. · 9.15 Impact Factor -
Article: Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen.
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ABSTRACT: Stavudine-containing antiretroviral regimens are widely used in developing countries. Stavudine-associated lipodystrophy commonly occurs, without a clear predictable pattern owing to the unknown interaction between stavudine and the host, among patients who received this regimen. The aim of this study was to determine the clinical risk factors and human leukocyte antigen (HLA) alleles associated with stavudine-associated lipodystrophy. A case-control, cross-sectional study was conducted for HIV-infected patients receiving stavudine-containing antiretroviral regimens. Clinical assessments for lipodystrophy by physical examination, anthropometry, and dual-energy X-ray absorptiometry were obtained. On the basis of their clinical assessment, the patients were classified into 2 groups: the case group (moderated to severe lipodystrophy) and the control group (absent to mild lipodystrophy). The clinical characteristics and allelic distribution of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 were compared between the case group and the control group, to determine the possible association with stavudine-associated lipodystrophy. There were 103 patients; 55 patients were in the case group, and 48 patients were in the control group. By use of forward stepwise logistic regression, the presence of HLA-B*4001 (odds ratio [OR], 14.05; 95% confidence interval [CI], 2.57-76.59; P=.002) and a longer duration of stavudine treatment (OR, 1.02; 95% CI, 1.00-1.04; P=.02) were significantly associated with stavudine-associated lipodystrophy, whereas a higher body mass index during treatment (OR, 0.73; 95% CI, 0.61-0.86; P<.001) was associated with a lower risk for lipodystrophy. HLA-B*4001 has a high specificity (95.8%) and a positive predictive value (88.9%) for lipodystrophy. HLA-B*4001 is a strong genetic risk factor for stavudine-associated lipodystrophy in HIV-infected patients in Thailand. HLA-B*4001 may be used as a genetic marker to predict which patients will develop stavudine-associated lipodystrophy, to avoid or shorten the duration of stavudine use. This finding needs to be confirmed in further replication studies.Clinical Infectious Diseases 02/2010; 50(4):597-604. · 9.15 Impact Factor -
Article: HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients.
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ABSTRACT: Investigation of a possible involvement of differences in human leukocyte antigens (HLA) in the risk of nevirapine (NVP)-induced skin rash among HIV-infected patients. A step-wise case-control association study was conducted. The first set of samples consisted of 80 samples from patients with NVP-induced skin rash and 80 samples from NVP-tolerant patients. These patients were genotyped for the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 by a sequence-based HLA typing method. Subsequently, we verified HLA alleles that showed a possible association in the first screening using an additional set of samples consisting of 67 cases with NVP-induced skin rash and 105 controls. An HLA-B*3505 allele revealed a significant association with NVP-induced skin rash in the first and second screenings. In the combined data set, the HLA-B*3505 allele was observed in 17.5% of the patients with NVP-induced skin rash compared with only 1.1% observed in NVP-tolerant patients [odds ratio (OR)=18.96; 95% confidence interval (CI)=4.87-73.44, Pc=4.6x10] and 0.7% in general Thai population (OR=29.87; 95% CI=5.04-175.86, Pc=2.6x10). The logistic regression analysis also indicated HLA-B*3505 to be significantly associated with skin rash with OR of 49.15 (95% CI=6.45-374.41, P=0.00017). A strong association between the HLA-B*3505 and NVP-induced skin rash provides a novel insight into the pathogenesis of drug-induced rash in the HIV-infected population. On account of its high specificity (98.9%) in identifying NVP-induced rash, it is possible to utilize the HLA-B*3505 as a marker to avoid a subset of NVP-induced rash, at least in Thai population.Pharmacogenetics and Genomics 01/2010; 19(2):139-46. · 3.48 Impact Factor -
Article: A model and risk score for predicting nevirapine-associated rash among HIV-infected patients: in settings of low CD4 cell counts and resource limitation.
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ABSTRACT: Rash is the most common adverse effect associated with nevirapine (NVP). We aimed to develop a model and risk score for predicting NVP-associated rash among HIV-infected patients with low CD4 cell counts. Cross-sectional study was conducted and 383 HIV-infected patients consecutively enrolled in the study. Of 222 patients in the training set, 116 (52.2%) were males and median (IQR) age was 35.2 (31.1-42.0) years. Median (IQR) CD4 cell count was 104 (35-225) cells/mm(3). Of these, 72 and 150 patients were in "rash" and "no rash" group, respectively. Four factors were independently associated with rash: a history of drug allergy (odds ratio (OR) 4.01, 95% confidence interval (CI), 1.75-9.20, P = 0.001), body weight <55 kg. (OR 2.02, 95% CI, 1.09-3.76, p = 0.026), not receiving slow dose escalation (OR 2.00, 95% CI, 1.06-3.77, p = 0.032), and no concomitant drug(s) (OR 2.48, 95% CI, 1.32-4.64, p = 0.005). Receiver-operator characteristic analysis yielded area under the curve of 71% and the goodness-of-fit statistics was 6.48 (p = 0.840). The variables were given scores of 14, 7, 7 and 9, respectively. A cutoff >21 points defined the high risk individuals which yielded specificity and positive predictive value of 99% and 69%, respectively, with OR of 3.96 (95% CI, 1.79-8.86, p = 0.001). A model and risk score for predicting NVP-associated rash performed well in this study population. It might be useful for predicting the risk of rash before NVP initiation among HIV-infected patients with low CD4 cell counts.The Open AIDS Journal 01/2009; 3:24-30.
