HCV co-infection and markers of liver injury and fibrosis among HIV-positive childbearing women in Ukraine: results from a cohort study

BACKGROUND: Ukraine's injecting drug use-driven HIV epidemic is among the most severe in Europe with high burden of HCV co-infection. HIV/HCV co-infected individuals are at elevated risk of HCV-related morbidity, but little is known about burden of liver disease and associated factors in the HIV-positive population in Ukraine, particularly among women. METHODS: Characteristics of 2050 HIV-positive women enrolled into the Ukrainian Study of HIV-infected Childbearing Women were described by HCV serostatus. Aspartate transaminase (AST) to platelet ratio (APRI) and FIB-4 scores were calculated and exact logistic regression models fitted to investigate factors associated with significant fibrosis (APRI >1.5) among 762 women with an APRI score available. RESULTS: Of 2050 HIV-positive women (median age 27.7 years, IQR 24.6-31.3), 33% were HCV co-infected (79% of those with a history of injecting drug use vs 23% without) and 17% HBsAg positive. A quarter were on antiretroviral therapy at postnatal cohort enrolment. 1% of the HIV/HCV co-infected group had ever received treatment for HCV. Overall, 24% had an alanine aminotransferase level >41 U/L and 34% an elevated AST (53% and 61% among HIV/HCV co-infected). Prevalence of significant fibrosis was 4.5%; 2.5% among 445 HIV mono-infected and 12.3% among 171 HIV/HCV co-infected women. 1.2% had a FIB-4 score >3.25 indicating advanced fibrosis. HCV RNA testing in a sub-group of 56 HIV/HCV co-infected women indicated a likely spontaneous clearance rate of 18% and predominance of HCV genotype 1, with one-third having genotype 3 infection. Factors associated with significant fibrosis were HCV co-infection (AOR 2.53 95%CI 1.03-6.23), history of injecting drug use (AOR 3.51 95%CI 1.39-8.89), WHO stage 3-4 HIV disease (AOR 3.47 95%CI 1.51-7.99 vs stage 1-2 HIV disease) and not being on combination antiretroviral therapy (AOR 3.08 95%CI 1.23-7.74), adjusted additionally for HBV co-infection, smoking and age. CONCLUSIONS: Most HIV/HCV co-infected women had elevated liver enzymes and 12% had significant fibrosis according to APRI. Risk factors for liver fibrosis in this young HIV-positive population include poorly controlled HIV and high burden of HCV. Results highlight the importance of addressing modifiable risk factors and rolling out HCV treatment to improve the health outcomes of this group

Young people in HIV care in Ukraine: a national survey on characteristics and service provision [version 2; peer review: 2 approved]

Background: Ukraine’s perinatally HIV-infected (PHIV) young people are ageing into adolescence/young adulthood and, alongside those with horizontally-acquired HIV infections, require transitional and other support services. We aimed to map this population and policies/service provision at specialist HIV centres, to inform future service development. Methods: A national survey was conducted of 28 HIV/AIDS centres on number, characteristics (age group, HIV acquisition mode) and care setting (paediatric/adult) of 10-24 year olds in HIV care in each of 24 regions in January 2016. Information was collected on policies/service provision at each centre. Results: Of 13,286 young people aged 10-24 years registered for HIV care nationally in Ukraine in January 2016, 1,675 were aged 10-18 years. Three-quarters of ≤19 year olds were PHIV, while 72% of 20-24-year-olds had sexually-acquired infection. Five regions accounted for two-thirds of 10-18 year olds in paediatric and 85% of 19-24 year olds in adult services. In 2015, 97 young people transitioned from paediatric to adult services nationally, typically at 18 years although with flexibility in timing at 17/28 centres. At 27/28 centres, horizontally HIV-infected young people aged <18 years began their HIV care in paediatric services sometimes (5) or always (22). Transition support most commonly consisted of a joint appointment with paediatrician and adult doctor, and support from a psychologist/social worker (both at 24/28 centres). Only 5/28 centres offered routine HIV care during the evening or weekend, and availability of integrated sexual/reproductive health and harm reduction services was uneven. Of 16/28 centres selectively following-up patients who did not attend for care, 15 targeted patients in paediatric services. Conclusions: Heterogeneity in the population and in service availability at the main regional/municipal HIV/AIDS centres has implications for potential structural barriers to HIV care, and development of services for this group

Catalytic functionalization of methane ²

À (3). The implications of these species in the catalytic process are discussed

Young people in HIV care in Ukraine: a national survey on characteristics and service provision [version 1; peer review: 2 approved]

Background: Ukraine’s perinatally HIV-infected (PHIV) young people are ageing into adolescence/young adulthood and, alongside those with behaviourally-acquired infections (BHIV), require transitional and other support services. We aimed to map this population and policies/ service provision at specialist HIV centres, to inform future service development. Methods: A national survey was conducted of 28 HIV/AIDS centres on number, characteristics (age group, HIV acquisition mode) and care setting (paediatric/adult) of 10-24 year olds in HIV care in each of 24 regions in January 2016. Information was collected on policies/ service provision at each centre. Results: Of 13,286 young people aged 10-24 years registered for HIV care nationally in Ukraine in January 2016, 1,675 were aged 10-18 years. Three-quarters of ≤19 year olds were PHIV, while 72% of 20-24-year-olds had sexually-acquired infection. Five regions accounted for two-thirds of 10-18 year olds in paediatric and 85% of 19-24 year olds in adult services. In 2015, 97 young people transitioned from paediatric to adult services nationally, typically at 18 years although with flexibility in timing at 17/28 centres. At 27/28 centres, BHIV young people aged <18 years began their HIV care in paediatric services sometimes (5) or always (22). Transition support most commonly consisted of a joint appointment with paediatrician and adult doctor, and support from a psychologist/social worker (both at 24/28 centres). Only 5/28 centres offered routine HIV care during the evening or weekend, and availability of integrated sexual/reproductive health and harm reduction services was uneven. Of 16/28 centres selectively following-up patients who did not attend for care, 15 targeted patients in paediatric services. Conclusions: Heterogeneity in the population and in service availability at the main regional/municipal HIV/ AIDS centres has implications for potential structural barriers to HIV care, and development of services for this group

Stereochemical aspects in the synthesis of novel N-(purin-6-yl)dipeptides as potential antimycobacterial agents

The synthesis of purine conjugates with natural amino acids is one of the promising directions in search for novel therapeutic agents, including antimycobacterial agents. The purpose of this study was to synthesize N-(purin-6-yl)dipeptides containing the terminal fragment of (S)-glutamic acid. To obtain the target compounds, two synthetic routes were tested. The first of them is based on coupling of N-(purin-6-yl)-(S)-amino acids to dimethyl (S)-glutamate in the presence of carbodiimide coupling agent followed by the removal of ester groups. However, it turned out that this coupling process was accompanied by racemization of the chiral center of N-(purin-6-yl)-α-amino acids and in all cases led to mixtures of (S,S)- and (R,S)-diastereomers (6:4). Individual (S,S)-diastereomers were obtained using an alternative approach based on the nucleophilic substitution of chlorine in 6-chloropurine or 2-amino-6-chloropurine with corresponding dipeptides as nucleophiles. The enantiomeric purity of the target compounds was confirmed by chiral HPLC. To test the assumption that racemization of the chiral center of N-(purin-6-yl)-α-amino acids occurs with the participation of nitrogen atoms of the imidazole ring via the stage of formation of a chirally labile intermediate, we obtained such structural analogs of N-(purin-6-yl)-(S)-alanine as N-(9-benzylpurin-6-yl)-(S)-alanine and N-(7-deazapurin-6-yl)-(S)-alanine. It was found that coupling of these compounds to dimethyl (S)-glutamate was also accompanied by racemization. This indicates that the imidazole fragment does not play a crucial role in this process. When testing the antimycobacterial activity of some of the obtained compounds, conjugates with moderate activity against the laboratory Mycobacterium tuberculosis H37Rv strain (MIC 3.1–6.25 μg/mL) were identified. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, AT part of Springer Nature.The work was financially supported by the Russian Science Foundation (Grant 19-13-00231). We are grateful to Dr. Marionella A. Kravchenko [Ural Research Institute of Phthisiopulmonology (National Medical Research Center, Ministry of Healthcare of the Russian Federation, Ekaterinburg, Russia)] for conducting biological trials. Analytical studies were carried out using equipment of the Centre for Joint Use ?Spectroscopy and Analysis of Organic Compounds? at the Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences

Manganese-Catalyzed Selective Oxidation of Aliphatic C-H groups and Secondary Alcohols to Ketones with Hydrogen Peroxide

An efficient and simple method for selective oxidation of secondary alcohols and oxidation of alkanes to ketones is reported. An in situ prepared catalyst is employed based on manganese(II) salts, pyridine-2-carboxylic acid, and butanedione, which provides good-to-excellent conversions and yields with high turnover numbers (up to 10 000) with H2O2 as oxidant at ambient temperatures. In substrates bearing multiple alcohol groups, secondary alcohols are converted to ketones selectively and, in general, benzyl C-H oxidation proceeds in preference to aliphatic C-H oxidation.

Mechanistic implications of the active species involved in the oxidation of hydrocarbons by iron complexes of pyrazine-2-carboxylic acid

The reactivity towards H2O2 of the complexes [Fe(pca)2(py)2]·py (1) and Na2{[Fe(pca3)]2O}·2H2O·CH3CN (2) (where pca− is pyrazine-2-carboxylate) and their catalytic activity in the oxidation of hydrocarbons is reported. Addition of H2O2 to 1 results in the formation of a dinuclear Fe(III)–(µ-O)–Fe(III) species characterized spectroscopically and by cyclic voltammetry. By contrast, treatment of 2 with H2O2 results in the formation of mononuclear iron(II) complexes, [Fe(pca)2(solvent)2]. The experimental results indicate that the catalytic activity of the starting complexes 1 and 2 is strongly dependent on the species formed in solution.