Efficacy of first-line ART regimens based on tenofovir in HIV-infected patients with pre-existing A62V mutation in reverse transcriptase.

INTRODUCTION: The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. MATERIALS AND METHODS: The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 ‒ patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 ‒ patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. RESULTS: There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. CONCLUSION: This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.

[Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation].

INTRODUCTION: The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted. The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors. MATERIALS AND METHODS: The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients. RESULTS AND DISCUSSION: The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely. CONCLUSION: Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

[Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1)].

INTRODUCTION: Tat protein is a major factor of HIV (human immunodeficiency virus) transcription regulation and has other activities. Tat is characterized by high variability, with some amino acid substitutions, including subtypespecific ones, being able to influence on its functionality. HIV type 1 (HIV-1) sub-subtype A6 is the most widespread in Russia. Previous studies of the polymorphisms in structural regions of the A6 variant have shown numerous characteristic features; however, Tat polymorphism in A6 has not been studied.Goals and tasks. The main goal of the work was to analyze the characteristics of Tat protein in HIV-1 A6 variant, that is, to identify substitutions characteristic for A6 and A1 variants, as well as to compare the frequency of mutations in functionally significant domains in sub-subtype A6 and subtype B. MATERIAL AND METHODS: The nucleotide sequences of HIV-1 sub-subtypes A6, A1, A2, A3, A4, subtype B and the reference nucleotide sequence were obtained from the Los Alamos international database. RESULTS AND DISCUSSION: Q54H and Q60H were identified as characteristic substitutions. Essential differences in natural polymorphisms between sub-subtypes A6 and A1 have been demonstrated. In the CPP-region, there were detected mutations (R53K, Q54H, Q54P, R57G) which were more common in sub-subtype A6 than in subtype B. CONCLUSION: Tat protein of sub-subtype A6 have some characteristics that make it possible to reliably distinguish it from other HIV-1 variants. Mutations identified in the CPP region could potentially alter the activity of Tat. The data obtained could form the basis for the drugs and vaccines development.

[Convulex and its place in epilepsy treatment with original valproates]. / Konvuleks i ego mesto v terapii épilepsii original'nymi val'proatami.

Therapeutic efficacy of three original valproates (convulex, depakine enteric and convulsofine) as well as direct cost of drugs for epilepsy treatment have been studied in 249 patients with long-term epilepsy with different types of epileptic seizures. The convulex efficacy was found to be lower than that of the other two drugs. Also, convulex reduces the frequency of seizures by 50-100% in 75% of the patients. During the convulex treatment of some types of seizures, remission was achieved in 81-90% of the patients. At the same time, the cost of treatment with convulex is 1.5 times lower comparing to that with depakine and is equal to that for convulsofine. The authors concluded the cost benefit of convulex treatment appeared to stimulate regional health departments and individual patients for wholesale and retail drug purchases.

[The diagnosis of staphylococcal infection by the determination of antigen-binding lymphocytes]. / Diagnostika stafilokokkovoi infektsii po opredeleniiu antigensviazyvaiushchikh limfotsitov.

Examination of 255 patients with different pyo-inflammatory and septic diseases revealed high effectiveness of the detection of staphylococcal infection by the determination of antigen-binding lymphocytes (ABL) in the indirect rosette-formation test with the use of specially designed staphylococcal erythrocytes immune reagents. ABL were detected in 63% of the examined patients, their content varied between 0.57% and 6.41% (which was, on the average, equal to 1.92 +/- 0.10%). The effectiveness of the method depended on the specificity of the staphylococcal reagent used in the test and on the time of examination of the patients. In patients with acute processes the determination of ABL permitted the diagnosis of staphylococcal infection before the activity of the corresponding serum antibodies could be measured. ABL were classified with T, B and "zero" populations of lymphocytes.

[Erythrocytic immunoreagents for diagnosing autoimmune disorders of the pancreas]. / Eritrotsitarnye immunoreagenty dlia diagnostiki autoimmunnykh povrezhdenii podzheludochnoi zhelezy.

Amidol sensitization of formalin-treated sheep red blood cells was found to be the optimal method for the preparation of an erythrocytic diagnostic agent from the summary antigen of the pancreas. Organ specificity of serum antibodies detection with the use of the developed diagnostic agent was provided by preliminary adsorption of the tested sera with rhesus-positive human red cells, group IV (AB). Use of this diagnostic agent in the neutralization test permitted a highly specific detection of the pancreatic antigen. Antigen-specific lymphocytes detectable in the indirect rosette-formation test with the erythrocytic diagnostic agent from the pancreatic summary antigen, based on chicken red cells were found highly specific.