[Cutaneous and visceral leishmaniasis in patients with HIV infection in Russia. Case report].

The article contains information on the problem of the combined course of HIV infection and leishmaniasis: a number of statistical and overview data in the world. It also presents a brief description of known cases of HIV patients with leishmaniasis in the Russian Federation. In all cases the diagnostics of leishmaniasis was difficult due to the lack of alertness of physicians to this illness, as well as poor knowledge of epidemiological situation of leishmaniasis. All patients with visceral leishmaniasis but one caught it during their stay in Crimea. Cutaneous leishmaniasis was described in HIV infection in the Russian Federation for the second time and is associated with the patient's residence in the Chechen Republic.

[Molecular epidemiological analysis of HIV-1 variants circulating in Russia in 1987-2015]. / Molekuliarno-épidemiologicheskii analiz variantov VICh-1, tsirkulirovavshikh v Rossii v 1987-2015 gg.

AIM: To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole. SUBJECTS AND METHODS: The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987-2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms. RESULTS: The nucleotide sequences of the pol gene were analyzed in 1697 HIV-1 samples and the findings were that the genetic variant subtype A1 (IDU-A) was dominant throughout the entire territory of Russia (in more than 80% of all infection cases). Other virus variants circulating in Russia were analyzed; the phenomenon of the higher distribution of the recombinant form CRF63/02A in Siberia, which had been previously described in the literature, was also confirmed. Four new recombinant forms generated by the virus subtype A1 (IDU-A) and B and two AG recombinant forms were found. There was a larger genetic distance between the viruses of IDU-A variant circulating among the injecting drug users and those infected through heterosexual contact, as well as a change in the viruses of subtype G that caused the outbreak in the south of the country over time in 1988-1989. CONCLUSION: The findings demonstrate continuous HIV-1 genetic variability and recombination over time in Russia, as well as increased genetic diversity with higher HIV infection rates in the population.

[Acquired immunodeficiency syndrome in Russia]. / Infektsiya, vyzyvaemaya virusom immunodefitsita cheloveka, v Rossii.

In 2015, the infection caused by human immunodeficiency virus (HIV) (HIV infection) dominated among life-threatening infections in Russians: it was first diagnosed in 98,177 Russians and 15,530 citizens of the Russian Federation died from HIV/AIDS, amounting to 45% of all deaths from infectious diseases in Russia. By the mid-2016, there were a total of 1,062,476 identified HIV-positive Russians, of whom 225,992 people died. The estimated number of HIV-infected patients in Russia approximated to 1% of the population, the highest prevalence of HIV being found in the age group of 30-40 years. The most active and expensive measures against HIV/AIDS in Russia are to examine the population for anti-HIV antibodies (29 million screenings per year) and to use in HIV-positive people antiretroviral therapy that was free of charge to more than 200,000 patients, i.e. nearly 25% of the registered Russians living with the HIV-infected. However, treatment coverage and quality are far from the target indicators that the international experts consider needed to reduce HIV prevalence and mortality. A wider program on HIV/AIDS, which includes a number of preventive measures with proven efficiency, as well as a program of promising researches and developments should be introduced in Russia.

[The sociodemographic portrait of a patient living with HIV and visiting AIDS centers in Russia]. / Sotsial'no-demograficheskii portret patsienta, zhivushchego s VICh i poseshchayushchego tsentry SPID v Rossii.

AIM: To study the sociodemographic data of people living with HIV who visit AIDS centers. SUBJECTS AND METHODS: A multicenter open-label study was conducted, which included the retrospective model "A patient's portrait". Outpatient records and questionnaires were analyzed in 7,000 patients older than 18 years of age who had visited AIDS centers in 27 regions of Russia from 1 April to 31 July 2014 and signed their informed consent form to participate in the study. RESULTS: There were women accounting for 49% of the study participants, including one transgender. Their mean age was 35.6 years; the median age was 34 (18-79) years. 77.4% of the women were infected sexually; 57.4% of the men were infected parenterally; the men who had sex with men accounted for 2.5% of the whole group (4.7% among the men). Only 9.8% of the respondents reported that they had used intravenous drugs in the past 6 months. 87.8% of the respondents had secondary and higher education; 68.6% of the patients (73% were male and 64% were female) were employed; 59.3% of the respondents were married or cohabited; 66.2% of the patients reported that they had had sexual contacts with one partner, 14.2% had not had sexual intercourses. 38.3% of the women and 48.8% of the men had a permanent HIV-negative sexual partner. 46% of the study participants had dependent minor children. 30% of the women had given birth to at least one child after the diagnosis of HIV infection. CONCLUSION: People living with HIV in Russia and visiting AIDS centers do not differ in main social and demographic indicators from the Russian Federation citizens of the same age who do not have HIV. They represent an economically and socially active population and participate in demographic processes so one of the public health priorities is to maintain and improve their quality of life.

[A panel of the drug-resistance HIV-1 clinical isolates].

A panel of 16 HIV-1 isolates was designed. Those isolates were isolated from patients undergoing HAART and developing resistance to the antiretroviral drugs. It was shown that the isolates were resistant to nucleoside RT inhibitors (retrovir, epivir) and non-nucleoside inhibitors (viramun). Isolates had stable replication activity. Average rate of cells expressing viral Ag was 14-20%. The infectious titer was 2.4 Ig TCID50. The sequencing showed that all isolates were of the subtype A dominating in the major part of Russian Federation. This panel could be used as the biotechnological base for studying antiretroviral drugs of new generation and for the design of experimental vaccines.

[Let sleeping dogs lie ..., but bail out your friend].

In 2013, 80,000 new cases of infection caused by human immunodeficiency virus (HIV) (HIV infection) were registered in Russia; there have been a total of as many as 850,000 notified HIV-infected cases in this country, which suggests that the HIV/AIDS epidemic becomes generalized. Of them, 150,000 people have died, most (22,000) cases in 2013, predominantly due to the late diagnosis of HIV infection and its delayed treatment initiation. The rise of new cases denotes that counteraction against the spread of HIV is inadequately effective; in this connection a further increase in morbidity and mortality rates should be forthcoming. However, the medical community has proved to be poorly trained to fight the epidemic; there is a lower awareness and knowledge about HIV infection among healthcare workers. To overcome the epidemic and its imminent negative implications, it is necessary to improve an epidemiological surveillance system, to introduce proven effective methods for the prevention of the disease, to increase patient access to current treatments, which will require not only higher direct expenditures on preventive measures, the creation of an infrastructure, and the purchase of medicaments and diagnostic agents, but also on the training and retraining of a large number of healthcare workers.

[The efficacy and safety of a therapy regimen including raltegravir and a fixed dose combination of lamivudine and abacavir in previously rifabutin-treated patients with tuberculosis and HIV infection].

AIM: To evaluate the efficiency and safety of using raltegravir (RAL) twice daily in conjunction with a once-daily fixed dose combination of abacavir (ABC)/lamivudine (3TC) in patients with HIV infection and active tuberculosis who have not previously received antiretroviral therapy (ART) and have taken rifabutin as antituberculosis therapy (ATT). SUBJECTS AND METHODS: The efficiency of ART was evaluated in 28 patients from a change in HIV RNA levels and from an increase in CD4+ lymphocyte counts during 48-week treatment that had been completed by 15 (53.6%) patients. The main reason for therapy discontinuation was that the patients returned to the use psychoactive agents. RESULTS: After 24 and 48 weeks of ART, the level of HIV RNA reached the undetectable values (less than 50 copies/ml) in 81.25 and 75% of the patients, respectively (according to an analysis including the patients who had completed the study in conformity with the requirements of the protocol). In only 2 patients, the virological therapy proved to be ineffective, which was likely to be associated with noncompliance with drug therapy. Following 24- and 48-week therapy, the increase in median CD4+ lymphocyte counts was 70 and 208.5 per µl, respectively. The concurrent use of ART and ATT caused positive changes in the lung skiagraphic pattern in 92.9% of the patients and complete resolution of lung tissue infiltration in 71.4%. Mixed infection ended in a fatal outcome caused by a progressive tuberculous process in 3 (10.7%) patients, in 2 of them within the first 8 weeks of treatment. The concomitant use of ATT including rifabutin and an ART (RAL + ABC/3TC) regimen was safe since one patient was noted to have a RAL-related adverse event (AE) (an allergic reaction) and caused the patient to discontinue therapy. ATT was not discontinued because of AE in any case. CONCLUSION: The ART regimen containing RAL and a fixed dose combination of ABC/3TC for adult patients with tuberculosis concurrent with HIV infection who are on combined therapy using rifabutin for tuberculosis may be recommended for the treatment of this category of patients.

The synthetic peptide from HIV increases functional activity of granulocytes in healthy subjects.

The influence of HIV lysate and eight synthetic peptides which are fragments of HIV proteins on the functional activity of polymorphonuclear neutrophils (PMN) was tested in 12 healthy subjects. PMN activity in nitroblue tetrazolium reduction (NBT test) and PMN chemiluminescence (CL) was studied. Only one peptide was found to result in a significant increase in NBT test on the whole blood. This was the oligopeptide (G-97) from the CD4-binding site of HIV-1 gp120. The increase of CL response of PMN in the presence of G-97 was revealed after only 15 min preincubation. The same effect in the presence of sera from healthy or infected patients at the persistent generalized lymphadenopathy stage was achieved by increasing the time of preincubation to 30 min. G-97 did not influence the proliferative activity of lymphocytes.

Clinical significance of HIV DNA in polymorphonuclear neutrophils from patients with HIV infection.

HIV DNA was detected by the polymerase chain reaction technique in polymorphonuclear neutrophils (PMNs) in 11 of 37 (29.7%) HIV-infected patients. A detectable level of HIV DNA in PMNs was more common in symptomatic than asymptomatic HIV infected patients (46.7% and 18.2%, respectively; p < 0.05). HIV DNA in PMNs was detected most frequently in patients with recurrent bacterial pneumonia or Pneumocystis carininii pneumonia. An association between HIV DNA in PMNs and a low CD4/8 ratio as well as high levels of immunoglobulins in the sera was noted. Detectable HIV DNA was found more frequently in patients with neutropenia than in those with a normal level of neutrophils in peripheral blood (44.4% and 28.0%, respectively; p < 0.05). These data suggest that infection of PMNs by HIV may be associated with PMN impairment during HIV infection.

Serological approaches to subtyping of HIV-1 in injecting drug users in Russia: evidence of subtype homogeneity at the main sites of the epidemic.

The aim of this study was to develop and evaluate a simple V3 peptide-based enzyme immunoassay (PEIA) for large-scale serotyping of HIV-1 specimens derived from injecting drug users (IDUs) in the Russian Federation. Two synthetic peptides were evaluated, named P1 (RKSIHIGPGRAFYATGD) and P2 (RTSVRIGPGQVFYKTGD), in an PEIA on 63 HIV-1 IDUs sera for which genotypes had been determined by heteroduplex mobility assay (HMA) and sequencing. The sensitivities of P1 (subtype B) and P2 (subtype A) were 87% and 75% respectively. Specificity of the assay was 100% for both peptides, with 100% predictive values of a monoreactive positive test for both peptides. Using the PEIA with peptides P1 and P2, we have serotyped 375 of 477 serum samples derived from IDUs in 4 main sites of the HIV-1 epidemic in Russia. The results demonstrated a high level of subtype homogeneity in all regions studied. In 3 of 4 territories, Tver' (n=345), and Rostov-on-Don (n=61) regions, and Krasnodar Kray (n=27), 100% of typable sera were found to belong to env subtype A. On the other hand, all specimens serotyped in the Kaliningrad region (n=38) belonged to env subtype B, and there is strong evidence that the recombinant gagAenvB virus which has caused the largest outbreak of HIV-1 in Russia is located in this region. At the present time another parental strain with gagBenvB genotype is of minor importance in the IDUs HIV-1 epidemic in Russia.

Psychosocial care for HIV-infected individuals in Russia.

The relatively small number of people known to be infected with HIV in Russia together with the absence of large numbers of affected people does not help to increase awareness of HIV infection as a social problem. This results in almost non-existent organized care systems for psychosocial support. Characteristics of psychosocial stress in HIV-infected individuals in Russia were studied over 3 years and ways to overcome it were examined. One-hundred-and-eighty-nine patients (120 men and 69 women) were studied. Our patients found support in attending health workers and from one another. Some characteristic features of the lifestyle of HIV-infected people in Russia are described. These include a search for non-traditional treatment methods; creating families (nine couples) or support networks between the infected; participating in public meetings in order to support those infected and pursue educational work, and meetings on for religious reasons. Social support may decrease the stress experienced by these people.

The direct binding of an HIV fragment with granulocytes from healthy subjects and infected patients.

The binding of the synthetic fragment from the CD4 binding site of HIV (gp 120) with polymorphonuclear neutrophils (PMN) in 13 healthy donors and 31 HIV-infected patients was studied using a biotin-streptavidin-texas-red complex. The largest percentage of PMN-bound peptide was reached at a final peptide concentration of 10 micrograms/ml. The increase of peptide concentration did not raise the per cent of positive PMN. Preliminary incubation of PMN or mononuclear cells with non-biotinylated peptide abolished subsequent binding of these cells with biotinylated peptide, while preliminary treatment of the cells by anti-CD4 monoclonal antibody did not lead to such abrogation. It was revealed that about 14% of PMN but no lymphocytes from healthy donors were able to bind peptide. The number of such PMN in HIV-infected patients was significantly less (6.3 +/- 8.9%, P less than 0.05). A connection between peptide-bound PMN and their functional activity was found. The percentage of such cells was 13.0 +/- 11.5% in patients with normal values in a stimulated nitroblue tetrazolium reduction test and only 2.6 +/- 2.8% in patients with low values in this test (P less than 0.05).

Modification of lymphocyte and monocyte functional activity by polymorphonuclear neutrophils in HIV infection.

The aim of this study was to determine whether polymorphonuclear neutrophils (PMN) can modify the immune response in HIV cases. Supernatants of PMN (PMNS) from 33 HIV-infected patients (16 with lymphoadenopathy syndrome, 17 with AIDS-related complex) were tested for their influence on the functional activity of lymphocytes and monocytes from 6 healthy donors. PMNS from another 6 healthy donors comprised a control group. It was found that PMNS from HIV-infected patients, but not from healthy donors, induced suppression of lymphocyte proliferative response and down-regulation of CD8 receptor expression on lymphocytes. Decrease of NK-cell cytotoxicity in the presence of PMNS from HIV-infected patients was the same as that from healthy donors. PMNS did not influence the production of anti-HIV antibody by lymphocytes from HIV-infected patients, as well as non-specific IgG by lymphocytes from healthy donors. PMNS effect on functional activity of lymphocytes was blocked completely after treatment of PMN by catalase and superoxide dismutase. At the same time PMNS from HIV-infected patients but not from healthy donors induced increased production of TNF-alpha by monocytes and up-regulation of monocyte phagocytosis. These effects were independent of catalase and superoxide dismutase and were not abrogated by antibody against IL-1, IL-8, TNF-alpha, IFN-gamma or IFN-alpha.

Influence of HIV antigens on functional activity of neutrophilic granulocytes in.

The effect of nine HIV antigens, including eight synthetic peptides, on the functional activity of granulocytes was studied using the reduction of nitroblue tetrazolium test (NBT test). Some peptides partly suppressed the functional activity of granulocytes. The most pronounced suppression was caused by ImVL (HIV-1 lysate immobilized on plates for ELISA) and SP-7 (a synthetic peptide from the gp41 protein of HIV-1). The degrees to which the functional activity of granulocytes was suppressed by ImVL and SP-7 was in inverse proportion to the specific antibody concentrations. No correlation was found between the reduction in the NBT test value and the amount of CD4+, CD8+ cells on CD4/8 ratio.

Mononuclear cells from HIV-infected patients produce factors which enhance functional activity of polymorphonuclear neutrophils from healthy subjects.

The influence of mononuclear cell supernatants (MNCS) from nine healthy donors and 35 HIV-infected patients (17 with lymphoadenopathy syndrome (LAS), 15 with ARC and three with AIDS) on functional activity of polymorphonuclear neutrophils (PMN) from healthy donors was investigated. MNC after short-term cultivation (24 h) produced factors which enhanced chemiluminescence (CL) and chemotaxis of PMN. This augmentation did not depend on stimulation of MNC by mitogens (lipopolysaccharide Escherichia coli (LPS) and concanavalin A (Con A)) or on activation of PMN by FMLP. After 48 h of cultivation only MNC stimulated by LPS produced these factors. MNCS from HIV-infected patients provoked a more pronounced augmentation of PMN CL compared with MNCS from healthy subjects. This enhancement was observed in patients at all stages of infection, but was more pronounced in patients with LAS. MNCS impact on PMN CL was not connected with proliferative activity of MNC but was correlated with the level of CD4 cells. It was shown that removal of adherent cells from MNC fraction resulted in decreased MNCS impact. Treatment of MNCS by antibody to IL-1 beta, IL-8, interferon-alpha (IFN-alpha) and tumour necrosis factor-alpha (TNF-alpha) did not decrease MNCS impact on PMN CL.