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.

Prevalence of HIV infection, access to HIV care, and response to antiretroviral therapy among partners of HIV-infected individuals in Thailand.

BACKGROUND: Health care providers usually focus on index HIV-infected patients and seldom obtain information from their partners. We aimed to determine HIV-preventative measures among couples, the prevalence of HIV infection, and treatment outcomes of partners. METHODS: This cross-sectional study was conducted in two hospital settings, a university hospital in Bangkok and a general hospital in northeastern Thailand, from January 2011-October 2015. Factors associated with serodiscordant relationships were determined by logistic regression. RESULTS: A total of 393 couples were enrolled for analysis; 156 (39.7%) were serodiscordant. The median relationship duration of serodiscordant couples was shorter than that of seroconcordant couples (6.4 years vs 11.6 years, p < 0.001). Of 237 HIV-infected partners, 17.7% had AIDS-defining illness, the median nadir CD4 count (interquartile range) was 240 (96-427) cells/mm3, 83.5% received antiretroviral therapy (ART), 98.3% had adherence > 95%, 90.3% had undetectable HIV RNA, and 22.9% had a prior history of treatment failure. There was no significant difference in condom usage in the prior 30 days between serodiscordant and seroconcordant couples. Factors of index HIV-infected patients associated with serodiscordant relationships were younger age (odds ratio [OR] 1.04 per 5 years; 95% confidence interval [CI] 1.01-1.06), receiving care at the general hospital (OR 1.73; 95% CI 1.08-2.78), a shorter duration of relationship (OR 1.04 per year; 95% CI 1.01-1.07), a higher nadir CD4 count (OR 1.06 per 50 cells/mm3; 95% CI 1.1-1.13), and not receiving a protease inhibitor-based regimen (OR 2.04; 95% CI 1.06-3.96). CONCLUSIONS: A high number of serodiscordant couples was determined. Partners' information should be retrieved as a holistic approach. Interventions for minimizing HIV transmission within serodiscordant couples should be evaluated and implemented.

Hepatitis B virus drug resistance in HIV-1-infected patients taking lamivudine-containing antiretroviral therapy.

A cross-sectional study was conducted in HIV-1-infected patients receiving lamivudine-containing antiretroviral therapy (ART) to determine the prevalence and risk factors of hepatitis B virus drug resistance (HBV-DR). HBV DNA and HBV genotypic resistance test were performed. Patients were categorized into two groups: with and without HBV-DR. There were 84 patients with a mean age (standard deviation [SD]) of 42.2 (10.2) years and 77% were males. Median (range) duration of ART and lamivudine use was 46 (3-177) and 40 (3-140) months, respectively. Median (range) CD4 cell count was 352 (49-790) cells/mm(3). Of all, 19 (23%) had HBV-DR with a median (range) HBV DNA of 2.56 x 10(7) (2.54 x 10(3)-11 x 10(7)) IU/mL. In univariate analysis, there were no differences in age, gender, ART regimen, liver function test, anti-HBc antibody, anti-HCV antibody between the two groups. Patients with HBV-DR had a higher proportion of positive HBeAg (68.4% versus 3.8%, p < 0.001). In multivariate analysis, positive HBeAg (odds ratio [OR) 16.64; 95% confidence interval [CI], 3.31-83.60] and duration of lamivudine use [per 6-month increment, OR 1.24; 95% CI, 1.06-1.36] were significant risk factors for HBV-DR. All 19 patients with HBV-DR had lamivudine resistance with the mutations as follows: M204V/I (95%), L180M/A181T (95%), L80V/I (47%), V173L (32%), and N236T (21%). Of these, 95%, 84%, 84%, and 0% of patients had HBV-DR to telbivudine, entecavir, adefovir, and tenofovir, respectively. HBV-DR is common in HBV/HIV-1 coinfected patients receiving lamivudine-containing ART without tenofovir. Positive HBeAg and longer duration of lamivudine use are risk factors for HBV-DR. In addition to lamivudine resistance, cross-resistance to other anti-HBV drugs is also frequently observed.

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.

Compliance with hepatitis B and hepatitis C virus infection screening among HIV-1 infected patients in a resource-limited setting.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important risk factors for mortality among HIV-infected patients. We assessed compliance with screening for HBV and HCV infection prior to initiation of ART in a resource-limited setting. Six hundred thirty-eight patients with a mean age of 38.4 years (53% males) were studied. Prior to initiation of antiretroviral therapy (ART) 371 patients (58%) were screened for HBV and 273 (43%) were screened for HCV infection. Of those screened, 9.7% had HBV infection and 8.8% had HCV infection. Given the relatively high prevalence of HBV and HCV infection among HIV-infected patients, screening for HBV and HCV infections prior to ART initiation should not be omitted in the resource-limited setting.