An analysis is presented of the evolution of HIV epidemic associated with comorbidity patterns specific for its different stages. At the stage of rapid HIV spread, HIV infection was mainly associated with drug addiction. Then large groups of HIV patients featuring multiple morbidity started to form. The main comorbid variants of HIV infection considered in the paper include HIV and co-infections including viral hepatitis and tuberculosis; HIV and malignancies; HIV and neurological diseases; HIV and drug and alcohol abuse; and HIV and mental disorders. Currently, HIV epidemic is associated with a high mortality rate despite of HAART. This warrants the development of novel approaches to the organization of medical and social care provision to HIV patients, expanding the scope of therapeutic drugs supply to treat comorbid conditions at outpatient facilities, and training other medical specialists, besides infectiologists, to engage them in treatment of HIV patients.

The procedures, advantages, and disadvantages of the phenotyping and genotyping methods for determination of HIV-1 tropism are reviewed. The results of a genotyping determination of HIV tropism and subtypes based on sequencing of the V3 region of the gene coding for HIV envelope gp120 glycoprotein from 98 patients are presented. Lifelong use of combined antiretroviral therapy results in the need to introduce novel classes of drugs, such as CCR5 antagonists, and novel test for HIV tropism. At present, the most convenient in the clinical practice are genotyping methods based on gp120 V3-loop sequencing, which are informative and affordable. One of advantages of genotyping is the opportunity to determine HIV tropism and subtype simultaneously. Accumulating the results of forecasting non-B HIV subtypes will make it possible, with time, to enhance the accuracy of using the method in patients infected with different HIV subtypes.

The aim of the study was to determine the clinical and laboratory criteria for forecasting the development of drug resistance in HIV patients. Materials and methods: A sample of 205 patients under ART was divided into two groups. Group 1 comprised 107 patients whose case histories included HAART failure according to virological parameters and whose test results included the presence of HIV strains resistant to one or several of antiretroviral drugs. Group 2 comprised 98 patients with no history of HAART failure. Results: The factors promoting resistance to HAART are patient’ low social status, alcohol and/or illicit drug abuse, and poor adherence to therapeutic regimens. With regard to HAART regimens, it was found that all NNRTI increase the risk of drug resistance not only to drugs of this group but also to NRTI. Protease inhibitors in most cases reduce the risk of drug resistance. An integral score model of resistance risk is suggested. The probability of drug resistance is minimal when the risk score is below 5 points, is significantly increased at 6-8 points, and is high when the risk score is above 8 points.

The analysis of 140 nucleotide sequences of pol gene fragments from HIV-1 variants circulating in seven territories of the Far-Eastern Federal District shows that dominating in the District is still HIV-1 subtype A1 (70,1%). Other HIV variants found are subtype B (7,1%), subtype C (3,6%), CRF01-AE (1,4%) and, sporadically, CRF03_AВ and CRF11_cpx. In 17,7% of cases, the recombinant subtype A/G form CRF02_AG has been found. HIV-1 resistance to three groups of ART drugs was studies in ART-treated and ART-naïve patients. The overall rate of drug resistance in the District 1,1%.

Timely diagnosis and treatment of HIV infection is complicated by the lack of motivation for diagnostics and therapy in marginalized populations. The objectives of the present study were to assess the causes and factors of the lethal outcomes among HIV patients. Materials and methods: Retrospective indiscriminating analysis of 812 lethal HIV cases registered in Omsk Region in 2012-2015. Results: The men to women proportion among the cases was 3:1. HIV diagnosis and death of HIV most often occurred in the age group 20 to 40 years. At diagnosis, the third clinical stage of HIV infection prevailed. Lethal outcomes were most often attributed to secondary diseases. The man follow-up time was 20 months. The causes of death were associated with the progression of HIV infection suggesting the lack of adherence to therapy among patients.

The time course and distribution patterns of combined HIV/TB infection in the Republic of Karelia over the last eight years were studied. Additionally, 127 case histories of HIV/TB patients related to the period from 2001 to 2015 were examined. It is found that the high prevalence of multiple drug resistance of M. tuberculosis (primary MDR prevalence is 46,5%) is associated with delayed diagnoses of combined HIV/TB infection (stage 4-5 HIV in 70% of cases). This factor in combination with the significant input of HIV/TB patients from the Federal Penitentiary System promotes the rapid spread of HIV/TB infection over the whole territory of the Republic. These features make it expedient to develop dedicated programs aimed at close monitoring of risk groups and at the social support for homeless people and for convicts set free after imprisoning. With account of the high rate of other concomitant infections, the atypical clinical and roentgenologic manifestations of TB upon immunosuppression, and the high rate of MDR, speeding up of TB diagnosis requires the use of molecular diagnostic tools, such as Gene-X-Pert, when TB is suspected in HIV patients.

Study objectives: Diagnostics and treatment of community-acquired pneumonia (CAP) and recovery from it in military personnel having coal mining in anamnesis. Material and methods: All patients examined were divided into two statistically matched study groups, each including 100 CAP patients, the main group with and the control group without coal mining in anamnesis. Results and discussion: Complaints about coughing were reported more frequently in the main group, and fever above 38° C was more frequent in the control group. Auscultation revealed focal pulmonary lesions equally often in both groups. Respiratory failure was more frequent in the main group. The mean in-hospital time was significantly higher, and the mean duration of respiratory failure remissions was lower in the main group. A significant decrease in the adaptation index was found only in the control group. Conclusions: Compromised adaptation to adverse and hazardous conditions of military service is likely to be caused in the main group by the prior occupation associated with alterations in the functions of the cardiovascular system and, probably, of the nervous system. After CAP, such servicemen are in need of rehabilitation with the main objective to ensure their adaptation to the conditions of military service and thus to enhance their workability and optimize their functional conditions.

The clinical manifestations of lesions of the nervous system found at different stages of HIV infection in most patients may be caused by compromised cell immunity, direct neurotoxic effects of HIV, and pathological immune responses. Despite of significant progress in therapy for HIV-associated neurological disorders since the highly active antiretroviral therapy had been introduced into clinical practice, the problem of drugs able to eradicate HIV and to influence autoimmune processes is still urgent. Therapeutic means rendering complex anti-infection and immunoregulatory effects include intravenous immunoglobulin administration (IIA), which can improve prognosis significantly in some cases of HIV-associated neurological disorders. The present paper briefly reviews literature about diagnostics and treatment of nervous system lesions in HIV patients. A case of HIV-associated myelopathy progression in a HAART-treated patient is considered in detail. Diagnostic algorithms and possible mechanisms of IIA effects in cases of HIV-associated neurological disorders are discussed.

The 5-years results of preventive chemotherapy (PCT) for tuberculosis in HIV patients in Sverdlovsk Region suggest that the rusk of manifestation of latent tuberculosis when CD4+ cell counts are below 200 ml^-1 is reduced 2,7 fold with isoniazid or isoniazid/pyrazinamide and 1,4 fold with antiretroviral therapy (ART). The combined use of PCT and ART reduces the risk 6,7 fold. Expanding PCT from phthisiology to the practice of AIDS Centers and of rooms of infectious diseases at polyclinics has increased from 43,9% to 58,4% the coverage of HIV patients, who have CD4+ cell counts below 200 ml^-1, with PCT, there having been no decrease in treatment effectiveness. The risk of lethal outcomes caused by TB is significantly reduced with PCT, especially if it is combined with ART.

The paper discloses the organizational structure and algorithm of health care provision to HIV patients in Leningrad Oblast. Because of somewhat delayed (2007) establishment of AIDS Center in Leningrad Oblast, HIV screening and HIV patients follow-up at dispensaries were under the responsibility of district hospitals. This system was preserved and supplemented with the coordinating functions of AIDS Center concerning ART drug supply and therapy prescription and laboratory monitoring of HIV treatment. This system may serve as a model of decentralized approach to HIV control.

Novel types of the 5’-norcarbocyclic analogues of nucleosides have been designed, and new biological targets and mechanisms of action of these compounds have been found. The first group of the analogues are derived from purine nucleosides. N¹-oxide-5’-noraristeromycin derivatives show an antiviral activity in a virus. The isosteric analogues of inosine-5’-monophoshate were weakly inhibitory towards inosine-5’-monophosphate dehydrogenase II and hepatitis C virus, but did not suppress M. Tuberculosis growth. The second group are 1-(4’-hydroxy-2’-cyclopentene-1’-yl)-uracil (HCPU) derivatives having substituents at 4’-hydroxyl and at carbon 3 of the heterocyclic core. The analogues were evaluated as HIV-1 reverse transcriptase inhibitors. It has been shown for the first time that 3,4’-substituted analogues of HCPU can act as the non-nucleoside inhibitors of reverse transcriptase of wild type HIV-1 (Ki 5 to 19 mkM) and HIV-1 mutants L100I (Ki 1 to 11 mkM) and K103N (Ki 8 to 55 mkM) referred to the first generation NNRTI resistant HIV-1 strains. The third group includes HCPU and 1,3-di-(4’-hydroxy-2’-cyclopentene-1’-yl)-uracil derivatives having different substituents (a halogen or 5-arylamine) at carbon 5 of their heterocyclic core. The compounds of this group proved to be potent inhibitors of the laboratory M. Tuberculosis strain H37Rv (MIC90 10 to 40 mg/ml) and the MS-115 strain (MIC90 5 to 20 mkM), which features multiple drug resistance against five first-line anti-tuberculosis: rifampicin, streptomycin, ethambutol, and pyrazinamide. A weak anti-HIV activity of these compounds has also been shown (Ki 60 to 11 mkM). The fourth group of the novel 5’-norcarbocyclic nucleosides are furopyrimidine analogues, which are modified at positions 4 and 5 of their uracil moieties. They were shown to inhibit the growth of different tumor cell lines at IC50 from 3 to 50 mkM.

Study objective was to assess the effect of data inconsistency on the quality of structural systemic analysis (SSA) models of reverse transcriptase inhibitors and to develop approaches to increasing the accuracy and predictive power of such models. Materials and methods: Structure-activity relationships in HIV-1 reverse transcriptase inhibitors were modeled using biologically active compound databases. Computer-assisted analysis and modeling of relationships between the structures and biological activities of chemical compounds allows predicting the activity of substances that were not studied experimentally, including even those only intended to be synthesized. Databases of biologically active compounds are extremely valuable sources for the selection of samples used to train SSA models. The quantitative characteristics of activity (IC50 and Ki) of a particular compound may be highly variable, especially if they have been determined at different laboratories, and this may cause considerable discrepancies in databases. Results: The adequacy of freely accessed and commercial databases to developing accurate and predictive SSA models for substances having an antiretroviral activity (HIV-1 reverse transcriptase inhibition) was assessed. The accuracy of SSA models was found to depend on the procedures of construction of a training sample. Certain limitation were found in databases used to construct training samples when sample entries have been testes under almost identical conditions. Therefore, it is expedient to develop a method for selecting low molecular weight compounds featuring low variability of their quantitative characteristics for being used in training of SSA models. Such method would increase the accuracy of SSA models employed in the design of novel antiretroviral substances.

Hepatitis B and C bringing to health care facilities makes threat to medical personnel engaged in their professional duties. The paper presents statistics about hepatitis B and C incidence rates, the risks of occupational injuries and the scope of vaccination against hepatitis B among hospital personnel in Saint Petersburg in 2009-2015.

Study objective: To estimate the total contribution of the allelic variants of polymorphic loci of human genome to the development of immunity to HIV in non-infected partners from HIV-discordant pairs by calculating the total genetic score (TGS). Materials and methods: In the case-control study, the case group comprised non-infected partners from 34 HIV-discordant pairs existing for not less than 5 years. The control age- and sex-matched group comprised 34 randomly selected confirmed sexually infected HIV patients. Whole blood samples were used to isolate genomic DNA by standard phenol-chloroform extraction using magnetic particles. Polymorphic loci were analyzed using PCR followed by PCR product detection in agarose gels. For CCR5-T303A and SDF-1 3'А loci, restriction-fragment size-polymorphisms were determined. For CCR2-V64I, allele-specific PCR approach was employed. Each subject was ascribed with individual scores of immunity to HIV according to the loci studies, and the total individual score was determined as the sum of all specific scores. The results were treated statistically using R programming tools. Results: The loci DC-SIGN-VNTR и CCR5-T303A in both groups were found to be comprised of only «normal» heterozygotes having genotypes 7,7 and T,T, respectively, that is, these two markers proved to be not polymorphic. In the case of the «control» marker NOS3-VNTR, each group was found to include a single homozygous bearer of a mutant allele (genotype 4, 4), and eight heterozygous bearers (genotype 4, 5). In the case of the polymorphic marker SDF-1 3'А, the case group had an increased number of heterozygotes (A, G), fourteen vs. nine in the control group, confirming our model of «heterozygote odds» for calculating the genetic score related to this locus: TGS values varied from 0 to 5 in case group and from 1 to three in the control group. In the case group, eight subjects (23,5%) had TGS≥4, whereas in the control group none had TGS≥4. The median TGS values were 3 in case group and 2 in the control group. The results suggest that the group of non-infected partners from HIV-discordant pairs differs from the group of sexually infected HIV patients. Conclusion: Our preliminary data confirm the adequacy of the TGS approach to case-control studies and the expedience of further studies, which will help to develop recommendation for clinics.