The Association of HLA-B*35 and GSTT1 Genotypes and Hepatotoxicity in Thai People Living with HIV.

Glutathione s-transferase (GST) is a family of drug-metabolizing enzymes responsible for metabolizing and detoxifying drugs and xenobiotic substances. Therefore, deletion polymorphisms of GSTs can be implicated in developing several pathological conditions, including antiretroviral drug-induced liver injury (ARVDILI). Notably, GST polymorphisms have been shown to be associated with ARVDILI risk. However, data on GST polymorphisms in the Thai population are limited. Therefore, this study investigated possible associations between GST genetic polymorphisms and ARVDILI development. A total of 362 people living with HIV (PLHIV) and 85 healthy controls from multiple centers were enrolled. GSTM1 and GSTT1 genetic polymorphisms were determined using polymerase chain reactions. In addition, HLA genotypes were determined using a sequence-based HLA typing method. After comparing GST genotypic frequencies, there was no significant difference between PLHIV and healthy volunteers. However, while observing the PLHIV group, GSTT1 wild type was significantly associated with a 2.04-fold increased risk of ARVDILI (95%CI: 1.01, 4.14; p = 0.045). Interestingly, a combination of GSTT1 wild type and HLA-B*35:05 was associated with a 2.28-fold higher risk of ARVDILI (95%CI: 1.15, 4.50; p = 0.02). Collectively, GSTT1 wild type and a combination of GSTT1 wild type plus HLA-B*35:05 were associated with susceptibility to ARVDILI in the Thai population.

Missed opportunities for earlier diagnosis of HIV infection in people living with HIV in Thailand.

HIV testing is the first step to making people living with HIV (PLHIV) aware of their status. Thailand is among the countries where antiretroviral therapy is initiated in PLHIV at the lowest CD4 cell counts. We aimed to quantify and characterize missed opportunity (MO) for earlier diagnosis of HIV infection in PLHIV in Thailand. The medical records of adults who were newly diagnosed with HIV between 2019 and 2020 at the two tertiary hospitals in Thailand were reviewed. A hospital visit due to an HIV clinical indicator disease but an HIV test was not performed was considered an MO for HIV testing. Of 422 newly diagnosed PLHIV, 60 persons (14.2%) presented with at least one MO, and 20 persons (33.3%) had more than one MO. In PLHIV with MO, the median (interquartile range) time between the first MO event and HIV diagnosis was 33.5 (7-166) days. The three most common clinical manifestations that were missed were skin manifestations (25.0%), unexplained weight loss (15.7%), and unexplained lymphadenopathy (14.3%). Anemia was a factor associated with MO for HIV diagnosis [odds ratio (OR) 2.24, 95% confidence interval (CI) 1.25-4.35; p = 0.018]. HIV screening reduced the risk of MO for HIV diagnosis (OR 0.53 95% CI 0.29-0.95; p = 0.032). In conclusion, MOs for earlier diagnosis of HIV infection occurred in both participating hospitals in Thailand. Skin manifestations were the most common clinical indicator diseases that were missed. HIV testing should be offered for patients with unexplained anemia. Campaigns for HIV screening tests should be promoted.

Vitamin D insufficiency and deficiency among HIV-1-infected patients in a tropical setting.

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.

Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Aeromonas hydrophila sepsis with septic embolism and rhabdomyolysis in a chronic iron overload haemodialysis patient treated with deferoxamine.

Aeromonas infection in humans is associated with certain underlying diseases, especially chronic liver disease or malignancy. However, Aeromonas infection associated with iron overload is rarely reported. We report a case of a 47-year-old female with end-stage renal disease on haemodialysis and on deferoxamine treatment for iron overload who developed Aeromonas sepsis with septic embolism and rhabdomyolysis. Although the patients with Aeromonas infection and rhabdomyolysis have been correlated with high mortality, this reported case survived. We suggest that a chronic haemodialysis patient on deferoxamine treatment for iron overload is vulnerable to Aeromonas infection. In such cases, the clinician should be alerted to the possibility of rhabdomyolsis, and frequent haemodialysis is necessary.

Streptococcus suis infection and risk factors for mortality.

OBJECTIVE: Streptococcus suis infection is a re-emerging zoonotic disease reported worldwide. This study is aimed to describe the clinical features and determine the risk factors for mortality of this life-threatening disease. METHODS: A retrospective cohort study was conducted among patients diagnosed with culture-confirmed S. suis infection in a tertiary-care hospital in Northern Thailand during 2005-2007. Risk factors for mortality were determined by Cox's regression analysis. RESULTS: There were 66 patients with a mean age of 52.9 years; 68% were males. The most common risk of S. suis infection was eating under-cooked pork (59%). Clinical presentations included acute meningitis (52%), sepsis (27%), septic shock (12%), endocarditis (8%), and septic arthritis (1%). Hearing loss was observed in 35% and was associated with meningitis. The overall mortality rate was 17%; 11% occurred in 24h. Cox's regression revealed that septic shock (p=0.014) and elevated alanine transaminase (ALT, p=0.013) were risk factors for mortality. CONCLUSIONS: S. suis infection is common in Northern Thailand, where people often eat raw pork, and commonly presents with acute meningitis or sepsis. The mortality rate is high. The risk factors for mortality are septic shock and elevated ALT. Awareness of this disease and public education are essentially needed.