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Introduction: One of the most urgent problem of modern medicine is the fight against the disease caused by the Human Immunodeficiency Virus (HIV) - HIV infection. The chemical compounds have improved the situation for infected people, but they are toxic, disrupt the metabolism and cannot eliminate the integrated virus from the body. The emergence of resistant HIV strains makes these treatments ineffective. Often, the death of HIV-infected people occurs as a result of the development of opportunistic infections caused by viruses of the Herpesviridae family. Therefore, the search for new therapeutic and preventive drugs that are less toxic and active against several viruses at the same time is relevant. Basidiomycetes, higher fungi, are a source of medicinal compounds that have antimicrobial properties, as well as antiviral ones. Humic compounds (HS) of various nature also have antiviral activity.The aim of the study was to obtain nontoxic compounds from the basidiomycete Inonotus obliquus and humic compounds from brown coals and to test their activity against viruses that are pathogenic to humans: HIV and Herpes Simplex Virus (HSV)., Material and Methods: The antiviral activity of melanin extracts obtained from the culture of the chaga fungus Inonotus obliquus and HS from the brown coal of the Kansko-Achinsk Deposit was studied using a model of MT-4 lymphoblastoid cells infected with HIV type 1 (HIV-1) strains and a monolayer culture of Vero cells infected with HSV type 1 (HSV-1) using virological and statistical research methods., Results and Discussion: It was found that all the studied compounds did not have a cytotoxic effect on cells at a concentration of 100 mcg/ml. It was shown that extracts of basidiomycetes and HS have antiviral activity against HIV-1 and HSV-1. EC 50 (50%-effective concentration) for HIV-1 was 3.7-5.0 mcg/ml, selectivity index 28-35. Antiherpetic activity was detected at a dose of 50-100 mcg/ml. The antiviral effectiveness of melanin compounds was established both in the «preventive» (2 hours before cell infection) and in the «therapeutic» regimen of drug administration, both for HIV-1 and HSV-1. The presence of antiviral activity of melanin and HS in relation to the RNA-containing HIV-1 virus and DNA-containing HSV-1 virus in our study coincides with the results of a number of authors in relation to influenza viruses, herpes virus, HIV, hepatitis B virus, Coxsackievirus, smallpox vaccine virus, which suggests that the type of nucleic acid in the virus does not play a fundamental role in the antiviral action of these drugs. It is also clear that HS is effective against both enveloped and non-enveloped viruses., Conclusion: In general, it can be concluded that melanin and humic compounds are characterized by low toxicity in the presence of both virucidal and antiviral activity. This allows us to consider the studied compounds as the basis for creating safe medicines that are effective against pathogens of various viral infections.

Unlabelled: The relationship between immunity disorders, destruction of intestinal barrier and development of systemic inflammation during antiviral therapy in patients with HIV infection is a topical issue in terms of suppression of virus replication and reduction of its role in the pathological process., Study Object: Blood of HIV-infected patients given antiretroviral therapy (n = 21) and non-infected volunteers (n = 20)., Methods: Identification of cells among CD4⁺ and CD8⁺ T-lymphocytes expressing markers of activation (CD38, HLA-DR), depletion (PD-1), and interleukin (IL) 7 receptor (CD127); measurement of blood levels of IL-6, neopterin, soluble CD14 (sCD14), intestinal fatty acid-binding peptide (I-FABP), and bacterial lipopolysaccharide. Correlation analysis of the dependence between cell immunity and systemic inflammation was performed., Results: HIV-infected patients had more activated CD4⁺ and CD8⁺ T-lymphocytes and CD4⁺ T-cells expressing PD-1 marker than non-infected subjects but less CD4⁺ and CD8+ T-lymphocytes expressing CD127. Blood IL-6, neopterin, soluble CD14, I-FABP and bacterial lipopolysaccharide levels in the former were higher than in the latter HIV-infected patients showed significant correlation of cell immunity parameters with blood neopterin and FABP levels., Conclusion: The process of activation, depletion, and regeneration of T-lymphocytes in. HIV infection are related to the destruction of intestinal barrier and systemic macrophage activation.

To the article a brief historical review and modern data are driven about the state of HIV-infection in the Odessa area, morbidity of HIV is analysed--the infected patients, passing treatment in stationary section of the Odessa regional centre from a prophylaxis and fight against AIDS during the last six year, drawn conclusion about efficiency of introduction of potent antiretroviral therapy.

The article presents analysis of activities concerning organization of pre-analytic stage of monitoring of HIV resistance to anti- retrovirus preparations on territories of the Privolzhskiy Federal Okrug. The medical records of patients receiving anti-retrovirus therapy and appointment cards to detect drug resistance of HIV from territorial centers of prevention and control of AIDS and infectious diseases are analyzed. The results of testing of specialists of service of prevention of AIDS/HIV with questionnaire "Characteristics of pre-analytical stage under implementation of molecular genetic and immunologic analyses" developed in the Privolzhskiy okrug center of prevention and control ofAIDS and samples of bio-tests obtained during coming-outs in regions of okrug were included into analysis too. The failures in implementation of pre-analytical stage were established. Hence, the subsequent decreasing of informativeness of analyses or inexpediency or even impossibility of application of testing of AIDS drug resistance. The recommendations are proposed concerning main directions of work to enhance pre-analytical stage of analysis of AIDS resistance to anti-retrovirus preparations.

By alkylation of uracil, thymine, cytosine, adenine, 6-chloropurine, and 2-amino-6-chloropurine with 5-chloro-1-(4-halogenophenyl)-1-pentanones novel derivatives of nucleic bases were obtained, their physicochemical properties were studied. The influence of synthesized compounds on HIV-1 integrase was investigated.

The paper presents the results of investigating the mechanisms of placental insufficiency and transplacental infection of infants born to HIV-infected mothers who have received specific antiretroviral therapy mothers and who have not.

The data on the antiviral action of the Ganoderma lucidum, Lentinus edodes, Grifola frondosa, Agaricus brasiliensis and other basidiomycetes metabolites are summurized. The metabolites of these species of basidiomycetes exhibit a direct antiviral effect on herpes simplex virus types I and II, human immunodeficiency virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus, Epstein-Barr virus, and others. Moreover, metabolites of basidiomycetes increased antiviral immunity.

Prevalence of the primary drug resistance mutations and resistance developed in patients receiving highly active antiretroviral therapies in the HIV-infected persons in the Privolzhsky federal district was studied. It was demonstrated that among the ART-naive HIV-positive patients there were no mutations leading to the development of resistance. A high level of the resistance to lamivudin, nevirapin, efavirenz was revealed among the persons receiving the antiretroviral therapy. As a whole, the frequency of mutations of resistance to nucleoside reverse transcriptase inhibitors (23.8%) and nonnucleoside reverse transcriptase inhibitors (26.9%) was much higher than to protease inhibitors (1.2%).

The paper gives the results of international trials of and guidelines for the use of maraviroc, the first CCR5 receptor antagonist, in treatment regimens for HIV-infected patients. The trials have convincingly shown that the maraviroc-containing antiretroviral therapy (ART) regimens are highly effective and safe for R5-tropic HIV-infected patients regardless of previous ART, baseline HIV RNA levels, and CD4+ lymphocyte count. Maraviroc can be recommended for HIV-infected patients who have previously received ART and who have been found to have a R5-tropic virus. The changes in the ART regimen and inclusion of maraviroc may be associated with both an ineffective previous treatment regimen and therapy-induced adverse events. In 2012, Russia's first reagent kit for the determination of HIV tropism was put to tests and registered at the Russian Inspectorate for the Protection of Consumer Rights and Human Welfare.

The efficiency of cycloferon liniment in combined treatment of herpetic infection in patients with latent form of HIV infection has been assess by observations of 40 patients divided into two groups. In the first group, the standard treatment was supplemented with the application of cycloferon liniment twice a day during 7 days; in the second group, the therapy was conducted according to standard recommendations. It was established that the application of cycloferon liniment in combination with standard therapy in patients with relapse of herpetic infection against the background of HIV infection ensures faster disappearance of general infectious syndrome, decreases the period of eruptions and the duration of local inflammations, and accelerates the epithelialization of erosions.

Current methods of HIV treatment can contain a progression of the disease; however they do not lead to a cure. Lifelong antiretroviral therapy is therefore necessary, leading to problems of cost and toxicity of chemical drugs. The recent advances in science have allowed a new approach to the HIV-treatment - gene therapy. In the present publication we focus on one strategy of the gene therapy called "intracellular immunization". The strategy is based on the introducing of antiviral genes into the HIV-sensitive cells. We highlight the mechanisms of action of various antiviral genetic agents and discuss some issues concerning target cells and genes delivery. Finally we summarize the results of certain gene therapy clinical trials.

Features of a clinical current of a sarcoma of Kaposi at a HIV-infected of patients are described. It is shown that treatment combined antiretroviral therapy, with application protease inhibitors, leads to full regress of skin elements in 12 months that allows to improve quality of life of patients, and adjusts on the favorable forecast.

Recombinant monoclonal antibodies (mAB) are a new class of medicinal preparations with the potential for wide application to the treatment of viral infections. Marked progress in the development of therapeutic mAB against respiratory syncytial influenza A viruses, West Nile virus, and some others has been achieved in recent years in contrast to HIV and hepatitis C pathogens. The main obstacle hampering this work is great heterogeneity and diversity of these viruses. Gene engineering technologies make it possible to modify mAB, modulate their efficacy, and create bi-specific mAB. This review presents data on the development and prospects for the application of mAB to prevent and treat viral infections.

Clinical and immunological parameters in the children with perinatal HIV infection were investigated in the dynamics of the long-term prospective observation. It was revealed, that all the HIV infected children had clinical signs of immunodeficiency and laboratory signs of combined damage of the immune system. The complex of therapeutic measures, including antiretroviral therapy, prevention of opportunistic and acute respiratory infections, rational immunotherapy to stimulate production of endogenous interferon and normalization of the balance of cytokines significantly reduced the frequency of the clinical manifestations of the infectious syndrome and improved the patients resistance to infections.

Substantiated in the paper is urgency of development of pathogenetically adequate immunotherapeutic approaches to the treatment of HIV-infection, that is supposed to have good prospects. Consideration is given to experimental and clinical-and-immunological findings concerning effects of different immunomoderivative drug preparations and of their synthetic analogues on the trigger mechanisms, with sequelae of their development in the cytokin-chemokin system outlined. A possibility is shown based on principle of our using with an immunotherapeutic purpose some cytokins, soluble receptors, antibodies to cytokins and receptors, those antibodies and ligands combined with toxins, chemical compounds affecting the synthesis of cytokin and other biologically active substances as well. Unspecific active immunotherapy is regarded as a good supplement to antiretroviral therapy preventing development of resistance to drugs.

The ability of protein isolated from (Trichoderma Rifai) and azydothymidine to inhibit the reproduction of HIV-virus was compared. The obtained experimental data have verified that Trichoderma Rifai protein is a promising human immunodeficiency virus (HIV) inhibitor.

Several novel phosphatidic acid derivatives of 3'-azido-3'-deoxythymidine and 2',3'-dideoxyinosine were synthesized, which contained dialkylphosphatidyl, dialkylthiophosphatidyl moieties, as well as diacylphosphatidyl moiety with either 14,14,14-trifluoro-12-oxatetradecanoyl or natural acyl residues inherent in egg yolk phosphatidylcholine. Diacylphosphatidyl derivatives of glycyrrhetinic acid were also prepared. All the synthesized compounds exhibited significant anti-HIV activity. The glycyrrhetinic acid derivatives are of special interest because of their low toxicity and a supposedly different mechanism of action.

The molecular and crystalline structures of deoxiribonucleoside analogs: 3'-O-methylthiomethylthymidine monohydrate dT(CH2SMe).H2O and 3'-O-methylsulphinylmethylthymidine dT(CH2SOMe) were determined. The space group of dT(CH2SMe).H2O crystals is P2(1), the parameters of the elementary cell are a = 10.417(1), b = 4.912(2), c = 15.969(2) A, beta = 107.23(1) degrees, V = 780.5 A3, Z = 2, R = 3.8%. The crystals of dT(CH2SOMe have a space group P2(1)2(1)2(1), the elementary cell parameters are a = 8.858(2), b = 9.303(1), c = 17.698(2) A, V = 1458.3 A3, Z = 4, R = 2.8%. The dT(CH2SMe) and dT(CH2SOMe) molecules are characterized by an anti-conformation relative to the glycoside bond (angles chi (O4'-C1'-N1-C2) are equal to -116.2 degrees and -148.8 degrees), a gauche(+)-conformation relative to the exocyclic bond C4'-C5' (angles phi CO (C3'-C4'-C5'-O5') are equal to 52.1 degrees and 41.1 degrees). The conformation of the furanose cycle in the dT(CH2SMe) molecule is described by C2'-endo-C3'-exo (P = 167.8 degrees, psi m = 34.8 degrees) and in the dT(CH2SOMe) molecule by C2'-endo-C1'-exo (P = 148.4 degrees, psi m = 35.4 degrees). The structures studied were compared with 3'-azido-3'-deoxythymidine (AZT) and thymidine.

In spite of continuous broad search for inhibitors of HIV reproduction among new nucleosides, there seems to be a certain crisis in the problem. One of the probable solutions could be based on the investigation of nucleotide and/or nucleoside 5'-triphosphates with modified carbohydrate and phosphate residues. The review analyzes the current state of the problem, examining of such types of compounds in cell-free systems with DNA polymerases and in HIV-infected cell cultures. The known data on the stability and metabolism of such compounds in cell cultures as well as in human serum are also analyzed.

It was established that 5'-phosphonates of 3'-azido-2',3'-dideoxythymidine (AZT) inhibit HIV reproduction in the MT-4 cell line as well as AZT. However, the viability of HIV-infected MT-4 cells after treatment with phosphonates was considerable higher that after AZT treatment. Inhibitory activities of 5'-phosphonates of 3'-fluoro-2',3'-dideoxythymidine (FLT) on HIV-infected MT-4 cells were rather low. The mechanism of action of these derivatives and prospects for their application for suppressing HIV infection are discussed.

The structure of 3'-methylamino-2',3'-dideoxyribosylthymine [ddT(3'NHMe)] was determined by X-ray analysis. The space group is P2(1)2(1)2(1). Cell dimensions are: a 5.132(1), b 13.718(1), c 16.947(2) A, V 1193.2 A3, Z 4. The structure was solved by directed methods and refined by the full-matrix least square method to R 4.8%. The molecule of ddT(3'NHMe) has anti-conformation with respect to the glycosidic bond (chi (O4'-C1'-N1-C2) = -106.7 degrees), C3'-endo-C4'-exo puckering of the sugar moiety (P -28.8 degrees, psi m -31.5 degrees) and gauche-gauche conformation about exocyclic C4'-C5' bond (psi(C3'-C4'-C5'-O5') 45.8 degrees). The structure of ddT(3'NHMe) was compared with those of 3'-amino-3'-deoxythymidine, 3'-azido-3'-deoxythymidine and natural thymidine.

Trials of clinically advantageous national inducers, thymus hormones, as well as human recombinant alpha 2-interferon were carried out in cultures of continuous lymphoblastoid cells H9/IIIB infected with HIV virus. The virus-inhibiting effect for HIV was observed with interferon in doses of 10-100 IU/ml. At a concentration of interferon of 1000 IU/ml, virus replication was inhibited completely, the interferon doses used exerting no marked toxic or antiproliferative effect on the cells. Human interferon inducers, poly(G).poly(C), PXL-6, dsRNA in concentrations of 50-100 micrograms/ml inhibited virus reproduction significantly. The highest antiviral effect was achieved with yeast dsRNA. The preparations of immunomodulators, thymarin, the 5th and 7th fractions of thymosin, noticeably stimulated proliferation of infected T-lymphocytes, reducing the relative number of cells carrying the virus-specific antigen. Combined use of preparations with different mechanisms of the antiviral effect may be advantageous in prevention and treatment of AIDS.

Perspectives of search, among natural and semisynthetic antibiotics, for inhibitors of different stages of the human immunodeficiency virus replication are discussed. The compounds which inhibit the virus absorbtion, reverse transcription, viral mRNA synthesis, viral protein translation or viral glycoprotein processing are presented.

Treatment of AIDS is a complicated problem since there is a limited set of preparations tested and most of them appear to be ineffective. Their main target is HIV reverse transcriptase. The data presented show that proteolysis inhibitors are able to inhibit HIV reproduction in cell culture. The compounds used in this study, gordox and kontrikal, are officinal drugs and therefore it is worthwhile to study their effect in patients with AIDS.

Studies were carried out on the effectiveness of ribamidil, sodium phosphonoformate, cortisone, and deksazon as inhibitors of human immunodeficiency virus (HIV) reproduction which was tested by immunofluorescence. The drugs were screened in H9/IIIB culture permissively infected with HIV virus, and in H9 culture subsequently infected with cell-free virus-containing culture fluid or by adding live cells from H9/IIIB culture. The latter variant was shown to be advantageous, especially if the available cultures did not produce large amounts of the virus. Because of the effectiveness of the immunosuppressants, the possibility of screening in lymphocyte cultures and selection of preparations exerting no true antiviral effect is discussed.

The effect of some Soviet chemical drugs (ribamydil, sodium phosphonoformate, acycloguanosine) as well as reaferon (genetic engineering alpha-interferon) and interferon inducers (lafarine, ridastine, rifastine, ENKAD) on HIV retrovirus reproduction was studied in cultures of continuous lymphoid cells H9 and a line of H9/IIIB cells persistently infected with HIV virus. The presence of viral antigen in the cells was determined by quantitative indirect immunofluorescence assays using a working dilution of 1:20 of a serum from an AIDS patient as the immune serum. The above studies showed that 3 drugs: ribamydil (50 micrograms/ml), phosphonoformate (120 micrograms/ml) and recombinant interferon (1000 IU/ml) were capable of statistically significant inhibition of retrovirus replication in continuous cultures of T-lymphocytes.

The methods of molecular hybridization are described using 32P-labeled plasmid pBHIO carrying the cloned HTLV-III provirus employed for the detection of HTLV-III-specific sequences in lines of T-lymphocytes from patients with acquired immune deficiency syndrome. The presence of virus-specific sequences was demonstrated in 13 out of 20 lines examined by the dot-blot hybridization method. The blot-hybridization method revealed differences in sites of Hind III restriction in 2 out of 6 lines studied. The possibility of combined infection of line No. 17 with two different variants of HTLV-III is discussed.

Action of three nucleoside analogues with azido-group on AIDS virus (human immunodeficiency virus--HIV) reproduction was studied in two cell species. Among these compounds there were 3'-azido-3'-deoxythymidine (Az-T), 3'-azido-3'-deoxyarabinothymidine (Az-AT) and 3'-azido-2',3'-dideoxy-5-methylcytidine (Az-dCMe). All compounds prevent cells against HIV infection, but Az-T action was expressed more strongly. The reason for the lower activity of the Az-AT and Az-dCMe bases is probably stipulated by their poor conversion to the corresponding 5'-triphosphates. Az-T 5'-triphosphate blocks HIV reproduction due to the inhibition of the viral reverse transcriptase.