Weerawat Manosuthi

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.

: Pneumonia is a leading cause of hospitalization and death among elderly adults. We performed a retrospective and prospective observational study to describe the etiology, clinical course, and outcomes of pneumonia for patients 60 years and older in Thailand. We enrolled 490 patients; 440 patients were included in the retrospective study and 50 patients were included in the prospective study. The CURB-65 score and a modified SMART-COP score (SMART-CO score) were used to assess disease severity. The median patient age was 80 years (interquartile range, 70–87 years); 51.2% were men. Klebsiella pneumoniae (20.4%) and Pseudomonas aeruginosa (15.5%) were the most common causative agents of pneumonia. A significant minority (23%) of patients were admitted to the intensive care unit (ICU), and mortality among this subset of patients was 45%. Most patients (80.8%) survived and were discharged from the hospital. The median duration of hospitalization was 8 days (interquartile range, 4–16 days). In contrast, 17.6% of patients died while undergoing care and 30-day mortality was 14%. Factors significantly associated with mortality were advanced age (P = 0.004), male sex (P = 0.005), multiple bacterial infections (P = 0.007; relative risk [RR], 1.88; 95% confidence interval [CI], 1.19–2.79), infection with multi-drug-resistant/extended-spectrum B-lactamase-producing organisms (P < 0.001; RR, 2.82; 95% CI, 1.83–4.85), ICU admission (P < 0.001; RR, 1.8; 95% CI, 1.4–2.3), and complications of pneumonia (P < 0.001; RR, 2.5; 95% CI, 1.8–3.4). Patients with higher SMART-CO and CURB-65 scores had higher rates of ICU admission and higher 30-day mortality rates (P < 0.001). These results emphasize the importance of Gram-negative bacteria, particularly K. pneumoniae and P. aeruginosa, as major causes of pneumonia among the elderly in contrast to other reports, Streptococcus pneumoniae is a common cause of pneumonia among elderly individuals worldwide. The SMART-COP and CURB-65 scores were developed to assess pneumonia severity and predict mortality of young adults with pneumonia. Few studies have examined the appropriateness of these scores for elderly patients with multiple comorbidities. A limited number of studies have used modified versions of these scores among elderly individuals. We found that Gram-negative bacteria has a major role in the etiology of pneumonia among elderly individuals in Southeast Asia. A significant proportion of elderly individuals with low CURB-65 scores were admitted to the hospital, indicating that hospital admission may reflect fragility among elderly individuals with low CURB-65 scores. The modified SMART-COP score (SMART-CO score) sufficiently predicted intensive care unit admission and the need for intensive vasopressor or respiratory support. A SMART-CO score ≥ 7 accurately predicted 30-day mortality.

HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (−14.4 ± 4.6 mg/dL, P = .002), LDL cholesterol (−13.7 ± 4.1 mg/dL, P = .001), and triglyceride (−30.4 ± 13.8 mg/dL, P = .03). A significant reduction in LDL cholesterol was also observed in the control group (−7.7 ± 3.8 mg/dL, P = .04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (−19.0 ± 4.6 vs. 0.2 ± 4.3 mg/dL, P = .003) and LDL cholesterol (−21.5 ± 4.1 vs. −6.8 ± 3.8 mg/dL, P = .009). There were no significant changes in HDL cholesterol or triglyceride levels in either group.

Data regarding risk factors for hospitalization among children with influenza B infection are limited. We conducted a retrospective study of 184 children with influenza B infection during October 2011 - September 2012 seen at Bamrasnaradura Infectious Diseases Institute, Thailand; clinical and laboratory data were compared between hospitalized and outpatient children. The numbers of hospitalized and outpatient children were 65 (35%) and 119 (65%), respectively. Most children (> 80%) were aged > or = 5 years. The median time from onset of symptoms to starting oseltamivir treatment was significantly longer among hospitalized than outpatient children (3 days vs 2 days, p < 0.05). The significantly more hospitalized children received antibiotics than outpatient children (43% vs 7%, p < 0.05). Complications were more common among hospitalized children than outpatient children (37% vs 2%, p < 0.05). Pneumonia and rhinosinusitis were significantly more common among hospitalized children than outpatient children (p < 0.05). Direct contact history, history of receiving an influenza vaccine, history of a previous influenza infection, body temperature, respiratory symptoms, gastrointestinal symptoms, headache and laboratory findings were not significantly different between the two groups (p > 0.05). In conclusion, delay initiation of antiviral therapy and medical complications (pneumonia and rhinosinusitis) were more common among hospitalized children with influenza B than outpatient children with influenza B in the studied population.

The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP). We compared the virological outcomes of (1) HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV); and (2) HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls). This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a) two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b) a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. A total of 559 patients were stratified into three groups: (a) Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161); (b) Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI) backbone therapy for a median of 7 days (n=82); and (c) Control, in which the subjects were naïve to antiretroviral therapy (n=316). The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4) and Control (6.6). However, differences were not statistically significant. Among the patients who had an acute allergic reaction to first-line NVP-based therapy and later began an EFV-based regimen, virological outcomes resulting from a staggered interruption of treatment (with a continuation of NRTI backbone therapy for 7 days after discontinuing NVP) did not differ from those of the patients who began an EFV-based regimen as their initial therapy (Control). However, the virological failure of Simultaneous Interruption was possibly higher than those of Control and Staggered Interruption.

To the Editor—Chang et al [1] raise a concern related to our study [2] regarding whether a dose escalation (lead-in) strategy of nevirapine is necessary in human immunodeficiency virus (HIV)-infected patients who are currently receiving rifampicin, because they already have undergone full induction of their cytochrome P450 system, provided that they have been taking rifampicin for a while. Nevirapine is an inducer of cytochrome P450 and also induces its own metabolism. This effect results in a reduction in the nevirapine elimination half-life from 45 to 30 h with repeated dosing after 2 weeks [3]. The recommended daily dose of nevirapine for adults is 200 mg twice daily [4]; this is preceded by a 2-week lead-in dose of 200 mg once daily because of the autoinduction of nevirapine hepatic metabolism. This lead-in strategy has been shown to reduce the frequency of rash [4].

Background. To our knowledge, to date, no prospective, randomized, clinical trial has compared standard doses of efavirenz- and nevirapine-based anti

To date, data on the durability of a regimen of stavudine, lamivudine and nevirapine are very limited, particularly from the resource-limited settings.