Prevalence of C-C chemokine receptor type 5 tropism among human immunodeficiency virus 1-infected patients in South Korea.

OBJECTIVE: The discovery of two main coreceptors for human immunodeficiency virus (HIV), C-C chemokine receptor type 5 (CCR5), and C-X-C chemokine receptor type 4 has led to a better understanding of the interaction between HIV envelope and host cells, and development of new therapeutic approaches. The purpose of this study was to estimate the prevalence of CCR5 tropism among HIV-1-infected Koreans and identify the predictors for CCR5 tropism. METHODS: We enrolled 250 HIV-1-infected subjects from four medical centers of three different cities in South Korea between April 2013 and May 2014. Genotypic assay for identifying coreceptor tropism of HIV-1 was performed with HIV RNA or HIV DNA. Nested polymerase chain reaction and population-based sequencing for the V3 region (HXB2 position 6225-7758) of the envelope were performed with HIV RNA or proviral DNA. Proviral DNA was used if the viral load of the subject was below 2000 copies/mL. Genotypic tropism was determined by a web-based bioinformatics tool (http://coreceptor.bioinf.mpi-inf.mpg.de/). RESULTS: Among 250 individuals enrolled, only 143 subjects could be analyzed for genotypic tropism assay with HIV RNA or proviral DNA. The prevalence of CCR5 tropism was 69.2% (N = 99). We could not identify any significant clinical or epidemiological predictors for CCR5 tropism among enrolled subjects. CONCLUSIONS: The prevalence of CCR5 tropism in HIV-1-infected Korean individuals was 69.2%. Since we cannot predict coreceptor tropism by clinical factors, tropism assay should be performed before treatment with the CCR5 antagonist.

Anion binding of short, flexible aryl triazole oligomers.

The flexible, electropositive cavity of linear 1,4-diaryl-1,2,3-triazole oligomers provides a suitable host for complexation of various anions. The binding affinities for various combinations of oligomer and anion were determined by (1)H NMR titrations. Effective ionic radius is found to be a primary determinant of the relative binding interactions of various guests, with small but measurable deviations in the case of nonspherical anions. Solvent effects are significant, and the strength of the binding interaction is found to depend directly on the donor ability of the solvent. A picture emerges in which anion binding can be effectively interpreted in terms of a competition between two solvation spheres: one provided by the solvent and a second dominated by a folded cavity lined with electropositive 1,2,3-triazole CH protons. Implications for rigid macrocycles and other multivalent hosts are discussed.

Safety and Efficacy of Ziagen (Abacavir Sulfate) in HIV-Infected Korean Patients.

BACKGROUND: Abacavir is a widely-used nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) infection. Mandatory postmarketing surveillance was conducted in Korea to monitor the safety and evaluate the effectiveness of Ziagen® (abacavir sulfate 300 mg; ViiV Healthcare, Middlesex, UK). MATERIALS AND METHODS: An open-label, multi-center, non-interventional postmarketing surveillance study was conducted from June 2010 to June 2016 to monitor the safety and effectiveness of Ziagen across 12 hospitals in Korea. Subjects older than 18 years taking Ziagen according to prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events after Ziagen administration. Secondary outcomes included the occurrence of adverse drug reactions, occurrence of serious adverse events, and effectiveness of Ziagen administration. RESULTS: A total of 669 patients were enrolled in this study, with a total observation period of 1047.8 person-years. Of these, 90.7% of patients were male. The mean age of patients was 45.8±11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse events, and four patients reported seven serious adverse events, without any fatal events. There was one potential case of an abacavir hypersensitivity reaction. Among the 97 adverse drug reactions that were reported from 75 patients, the most frequent adverse drug reactions included diarrhea (12 events), dyspepsia (10 events), and rash (9 events). No ischemic heart disease was observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under 50 copies/mL after 24 months of observation with abacavir administration. CONCLUSION: Our data showed the safety and effectiveness of Ziagen in a real-world setting. During the study period, Ziagen was well-tolerated, with one incident of a clinically suspected abacavir hypersensitivity reaction. The postmarketing surveillance of Ziagen did not highlight any new safety information. These data may be helpful in understanding abacavir and the HIV treatment practices in Korea.

Effect of ketoconazole on lobeglitazone pharmacokinetics in Korean volunteers.

PURPOSE: Lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, is metabolized primarily by the cytochrome P450 (CYP) 3A4 isoenzyme. Individuals concomitantly taking lobeglitazone and a CYP3A4 inhibitor may experience some adverse effects secondary to increased systemic exposure to lobeglitazone. To address such potential concern, we evaluated the effects of ketoconazole, a prototypic CYP3A4 inhibitor, on the pharmacokinetic (PK) properties and associated adverse effects of lobeglitazone. METHODS: A PK drug-drug interaction study was conducted in healthy individuals between 20 and 45 years old in a randomized, open-label, 2-way crossover design. Even though the PK study was performed on a single dose of lobeglitazone, multiple ketoconazole doses were given to ensure that the full extent of inhibition of CYP3A4 was maintained during the PK sampling. All study participants received a single oral dose of lobeglitazone 0.5 mg with or without 9 oral 200-mg doses of ketoconazole pretreatment twice daily. The primary PK parameter end points (AUC and Cmax) were estimated using noncompartmental analysis, and the 90% CIs for the geometric mean ratios (ratio of lobeglitazone and ketoconazole to lobeglitazone alone) were investigated. Tolerability (adverse events, vital signs, ECG, and laboratory tests) was also assessed. FINDINGS: A total of 24 Korean men (mean age, 26 years; age range, 20-32 years; mean weight, 68 kg; weight range, 59-81 kg) completed the study and were evaluable for lobeglitazone PK properties and tolerability. The mean (SD) Cmax values of lobeglitazone with and without ketoconazole were 49 (7) ng/mL and 48 (6) ng/mL at 1.5 and 1.0 hours after dosing, respectively. The mean (SD) AUC∞ values were 532 (117) ng·h/mL and 405 (110) ng·h/mL, respectively. Although the Cmax was not significantly affected, the geometric mean ratio for AUC∞ was increased by a point estimate of 1.33 (90% CI, 1.23-1.44). A single oral administration of lobeglitazone 0.5 mg with or without ketoconazole pretreatment did not produce any clinically significant adverse effects on vital signs, 12-lead ECG profiles, or laboratory tests. IMPLICATIONS: The administration of lobeglitazone, 0.5 mg alone or in combination with multiple doses of ketoconazole, was generally well tolerated. The systemic exposure of lobeglitazone was increased to a modest extent by pretreatment with 9 twice-daily doses of ketoconazole. Clinicaltrials.gov identifier: NCT01330563.