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HIV Infection and Immunosuppressive Disorders

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Vol 11, No 4 (2019)
https://doi.org/10.22328/2077-9828-2019-11-4

EDITORIAL

7-19 1176
Abstract
The aim of the study was to analyze the results of long-term antiretroviral therapy (ARV) in patients with HIV-infection basing on epidemiological, clinical and economical parameters in the Northwestern Federal District (NFD) of Russia. Materials and methods. Epidemiogical analysis was conducted using the data of reports from 10 NFD regions in the period from 2005 to 2018: morbidity rate, prevalence of HIV-infection, number of people living with HIV-infection (PLWH) and being under regular medical  check-up. For clinical analysis were used some key indices of ARV effectiveness such as patients’ therapy coverage, clinical stages of HIV-infection, mortality rate and lethality rate in patients. Health costs were calculated basing on ARV procurement in the District from federal and regional programs as well as from funds allocated on diagnostic products and prevention programs. Study results. On the top of  administered ARV, rates of mortality and prevalence of HIV-infection in the RF and NFD had increasing tendency. The rate of mortality in PLWH increased in several times while the lethality rate changed insignificantly. Number of PLWH on the stage of clinical signs grew sixfold reaching 63,1%. Questionnaire survey was held in 74 infectious disease physicians with the following estimation of values of some reasons of low effectiveness of ARV and  transformation of epidemic into severe and comorbid forms. By reason rating, low ARV coverage in patients was the most common, late detection of HIV-infection and treatment onset, poor adherence and therapy discontinuation, qualified staff shortage, low accessibility of medical organizations, insufficient choice and quality of ARV. In considering financial costs on ARV, insufficient appropriation of funds and insufficient support of other activities including organizational and preventive measures were revealed.

ANALYTICAL REVIEW

20-29 3275
Abstract
Background. Highly active antiretroviral therapy (ART) has increased the life expectancy of people living with the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Advances in scientific knowledge and, in particular, in the management of an HIV-infected pregnant woman have also reduced the risk of mother-to-child transmission of HIV. Aims. Consider the current problems of gynecological and reproductive health disorders and the pathophysiological aspects of these disorders in HIV-infected women. Methods. Review of Russian and international scientific publications related to gynecology, reproductive health and HIV infection from indexed online journals and relevant websites using Pubmed and  Google search from 1990 to March 2019. Results. In recent years, the proportion of HIV-infected women has increased and the role of sexual transmission of infection has increased, as well as the active involvement of women of reproductive age in the HIV epidemic. In HIV-infected pregnant women who did not receive HAART, the frequency of obstetric complications, labor and adverse outcomes in children is increased. HIV infection can reduce the fertility of women at any stage of the disease, marked violations of the menstrual cycle and ovulation, reduced ovarian reserve and the quality of oocytes. In HIV-infected patients, weight loss and dystrophy, impaired thyroid function, adrenal glands and hypogonadism are recorded. Violations of the menstrual, ovulatory function can occur for a variety of reasons that are not directly related to their illness, but to multiple stressors. HIV-positive women suffer from increased frequency and severity of pelvic infections and precancerous and malignant lesions of the cervix. Conclusions. Gynecological, reproductive needs, as well as the specifics of monitoring an HIV-positive woman are not sufficiently assessed, are not optimal and are largely ignored, which can negatively affect their quality of life and efforts to combat the HIV epidemic.


ORIGINAL STUDIES

30-39 941
Abstract

The aim of the study is to assess the incidence and causes of maternal mortality affected by HIV infection in Saint-Petersburg. 

Materials and methods. All cases of the maternal mortality were accounted from the beginning of the epidemic of HIV infection in the city.

Results. In Saint Petersburg, the first case of maternal mortality due to HIV infection was registered in 2002. Through 2002 to 2015, 164 cases of maternal mortality were registered. 31 of the cases were due to HIV infection (18,98±9,4%). So the number of these cases was 31 by the end of 2015. A high incidence of HIV infection in combination with injecting drugs (67,0±8,4%) and with chronic forms of parenteral viral hepatitis (58.0±8.8%) was reported. Drug addiction associated with HIV infection induced a high incidence of the angiogenic sepsis progression, which became the most common mortality factor (in 12 out of the 31 cases). AIDS-related co-infections (generalized forms of tuberculosis, pneumocystis pneumonia) caused the death of another 12 women. The total share of the infection as the cause of maternal death was 80,6±7,2%. In most patients, combinations of various AIDS-indicative states were reported: generalized cryptococcosis, necrotic toxoplasma encephalitis, chronic isosporosis, cachexia, oropharyngeal and esophageal candidiasis and more. Liver lesions up to cirrhosis were identified in 14 cases of co-infections of HIV/HCV and HIV/HCV+B. At the same time, the effect of HIV on progression and retrogression of obstetric pathogenic behavior was not reported. Obstetric complications occurred in only two patients hospitalized with the irreversible consequences of eclampsia (stroke and abruptio placentae complicated by cortical necrosis). These pregnant women did not seek medical help until hospitalization. In summatioin, 18 women had never sought medical help during pregnancy, which indicates the importance of social factors in pregnancy and childbirth outcomes.

40-50 778
Abstract
The objective of the survey: to analyze clinical, psychosocial and personal status in women co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), and their alcohol addiction. Materials and methods: the check-up of 191 surveyed women with HIV and HCV co-infection taking into account epidemiologic evidence, laboratory parameters: immunologic (CD4 lymphocyte count), virological (HIV and HCV RNA, HCV genotype) and complete and biochemical blood count was made. Detailed check-up of psychosocial and narcological status with the following assessment of alcohol use in 166 surveyed women was made; clinical, laboratory (ethyl glucuronide (EtG) determination in urine and carbohydrate-deficient transferrin (CDT) determination in serum), and instrumental methods. Results: Mean age of patients was 34,9±3,9 years. Most women (88%) had satisfactory social status. Most women had a long-standing co-infection. 3,7% of women were in the subclinical stage of HIV infection, 92.1% had stage 4A, 4B — 11% and 4B — 11%. The median number of CD4 lymphocytes was 470 cells/μl. 92,2% received ART, and 96,7% of women showed a high rate of treatment compliance. Among the prevalent HIV-associated diseases were candidiasis (53,2%) and viral infections (8,1%) and bacterial diseases (3%); a high percentage (15%) of past tuberculosis of various localization was noted. In 89,9% of women, a high replicative activity of HCV was detected in the blood. According to the results of indirect liver elastometry, 98,3% had minimal and moderate fibrosis (METAVIR ≤F2). 86,9% of patients showed total bilirubin level within the normal range, median alanine aminotransferase (ALT) was 62 cells/μl and median aspartate aminotransferase (AST) was 48 cells/μl. Comorbid infectious and non-infectious diseases were diagnosed in 65,4% of women. Antiviral therapy (ART) of chronic hepatitis C was performed in 4,7% of surveyed women who received the combination of pegylated interferon (pegIFN) and ribavirin. Mean history of psychoactive drug use was 7,2±4,1 years. By the time of survey, 96,4% of women denied use of any psychoactive drugs other than alcohol. In past medical history, 81,9% of patients used opioids, regular use of alcohol with the following addiction syndrome was diagnosed in 88,6% of patients. Increasing CDT concentration was revealed in 3 patients and in 3 cases, this parameter was within borderline unstable zone. Under assessment of psychopathologic status, prevalent psychopathologic syndromes were insomnia, psychoorganic syndromes and anxiety. According to aggression scale, high indices by «relational aggression»,  «irritation», «grievance», «suspicion», «guilt». Prevalent types of attitude to HIV-infecton were  ergopathic, sensitive, anosognosic.
51-60 7456
Abstract
Introduction. In patients with HIV infection frequency lesions of the nervous system stage in second place after the immune system, at the same time, strokes account for 1–5% of all lesions of the nervous system in HIV infection. The incidence of strokes in people under the age of 45 with AIDS is 10 times higher than in general population of people at the same age. Supposed that the role of HIV-associated vasculopathy and opportunistic infections is increasing the risk of stroke. The purpose of the study was to study features course of stroke in patients with HIV infection, hospitalized to vascular centers, depending on the type of stroke and identifications risk factors of cerebrovascular diseases (CeVD). Materials and methods. Studies were conducted in 73 patients with stroke, hospitalized for emergency reasons in vascular centers of St. Petersburg. In 33 (45,2%) patients was identified HIV infection, average age 49±11 years (group 1); 40 (54,8%) people without HIV infection, average age 49±7 years made up group 2. Depending on the type of stroke, hemorrhagic (HS) or ischemic stroke (IS), groups 1 and 2 were divided into subgroups. All patients were examined according to сase management program, which provides clinical, laboratory, neuroradiological, ultrasound research methods. HIV-infection was identified by laboratory research methods — ELISA and immunoblotting with determination of antigens and antibodies to HIV. Stages of HIV infection were determined according to the classification of V. I. Pokrovsky in a modification of the Federal scientific and methodological center for the prevention and control of AIDS. Results. This study was to identify the prevalence in group 1 proportion of patients with 3rd stage of HIV infection. Hemorrhagic stroke in the 1st group was characterized by a meningeal syndrome and thrombocytopenia, ischemic stroke (IS) — headache syndrome, lymphopenia, thrombocytopenia, increased ESR, ALT and AST enzymes, and smaller proportion of cardioembolic strokes, also insignificant regression compared neurological symptoms in patients without HIV infection (p<0,05). Conclusion. The most significant risk factors of CeVD in patients with HIV infected are diseases of the cardiovascular system with a smaller proportion of patients with coronary heart disease in patients with IS and cerebral arteriosclerosis. We can assume a significant role of the pathogenic effect HIV on hemostatic system and vascular endothelium, on increasing the risk of developing vascular accidents in patients with HIV infection. Smaller regression of neurological symptoms and hard course of disease in HIV infection associated with secondary opportunistic diseases, co-infections, late hospital admissions, hemostasiological disorders and in most cases the absence of HAART.
61-69 826
Abstract
Objectives: to analyze the association between genetic polymorphisms of Toll-like receptors (TLR) and mannose-binding lectin (MBL) and active tuberculosis in HIV-infected patients to consider the possibility of using genetic markers as a way to personalize the chemoprophylaxis of tuberculosis in this category of patients. Materials and methods: The study enrolled 171 patients (85 HIV-infected, 86 HIV/TB co-infected patients). Single nucleotide polymorphisms (SNP) in the TLR4 (rs4986790), TLR2 (rs5743708) and MBL2 (rs5030737, rs1800450, rs1800451) were genotyped by real-time PCR and pyrosequencing. Data about epidemiological risk factors were obtained from epidemiological anamnesis. Immune status was assessed by the level of CD4+ T-cells count. Results: Statistically significant association with active tuberculosis was identified for the genotype AG of TLR4, rs4986790 (OR=5.2; 95% CI: 1,8–14,6, p=0,002). Multivariate analysis shows that close contact with TB patientand status of ex-prisoner increased the risk of active tuberculosis 5,2 times (OR=5,2; 95% CI: 1,4–18,5, p=0,012 and OR=5,2; 95% CI: 1,5–17,7, p=0,009, respectively); CD4+ T-cell count more than 200 cells/mm3 exerted protective effect and reduced the risk of developing TB 5 times (OR=0,2; 95% CI: 0,1–0,5, p=0,001). The genotype AG of TLR4, rs4986790 increased the risk of active tuberculosis 3,7 times (OR=3,7; 95% CI: 1,1–13,1, p=0,046). Conclusion. The G allele of TLR4, rs4986790 can be considered as an independent risk factor for active tuberculosis in HIV-infected individuals. These results need to be confirmed by further investigations on large samples.



70-78 1120
Abstract
Abstract. The issues of concomitant pathology of HIV infection and tuberculosis are becoming increasingly relevant in the period of improving the epidemiological situation of tuberculosis. HIV-associated tuberculosis is given more attention due to the peculiarities of the processes characterized by generalization, progression and high lethal outcomes. Objective. The purpose of this work is to study the characteristics of tuberculosis in patients with HIV infection in a region with a high prevalence of HIV infection with fatal outcomes. Materials and methods. For a comparative analysis, depending on the outcome of the disease, 2 groups were formed: 1st group — 70 patients with tuberculosis and HIV infection (tuberculosis/HIV) who died within a month after admission to the tuberculosis hospital (main group), 2nd group — 70 tuberculosis/HIV patients were discharged from the hospital with improvement (comparison group). All patients received treatment in accordance with clinical guidelines. In statistical calculations, the Pearson c2-criterion or the c2-criterion with the Yeats correction with the number of degrees of freedom f=1 (f=(r–1)×(c–1)) was used. The level of significance was taken as a value of 0,05 or less. Results. In the first group, tuberculosis was more often detected upon admission to non-main hospitals (c2=5,28; р=0,0216), diagnosed with pneumonia (c2=9,46 р=0,0021) in the absence of fluorography in the current year. Mortality was more common in people under the age of 30 years who had no family (c2=18,72; p=0,00001) who were in prison (c2=7,96; p=0,0048) and led an antisocial lifestyle. An analysis of the manifestations of tuberculosis revealed no differences that determine the lethal outcome. The difficulty of diagnosing tuberculosis occurred when the CD4+ level was less than 300 cells. Comorbidity of tuberculosis and HIV infection is characterized by a commonality of many clinical manifestations regardless of the outcome. The presence of burdened social status increases the likelihood of dying with concomitant HIV/TB diseases.

Diagnostics, laboratory service

79-90 979
Abstract
Introduction. The HIV epidemic remains the most devastating in the history of mankind, despite comprehensive preventive measures. The HIV pharmacological resistance to several groups drugs at once is particular importance since this significantly reduces the therapy possibilities. Due to the low adherence to the treatment of patients certain categories, as well as the HIV drug-resistant transmission under various conditions possibility, treatment may not give positive results in 16–27% of patients who did not receive ART and in 50–70% of previously treated patients. The aim of our work was to evaluate the molecular-epidemiological structure and pharmacoresistant HIV variants in patients with antiretroviral therapy virologic failure in Arkhangelsk. Materials and methods. To evaluate the molecular-epidemiological structure and pharmacoresistant HIV variants in 76 HIV-infected patients with virologic failure of antiretroviral therapy from the Arkhangelsk region, HIV polymerase gene (pol) nucleotide sequences were analyzed. Results. In the examined group, HIV subtype A6 (IDU-A) prevailed (89,5%) compared with subtype B (9,2%), in one case (1,3%) the variant CRF03_AB was detected. For 86,8% of patients, resistance to any drugs was determined. Including resistance to protease inhibitors mutations — 33,3%, to revertase inhibitors — 92,4%. Isolates with pharmacoresistance only to NRTIs amounted to 16,6%, to NNRTIs 1,5%, to PI 10,6%, simultaneously to PI and NRTIs 12,1%, to NRTIs and NNRTIs 46,96%, to all three groups of drugs at the same time — 12,1%. The most common mutations are drug resistance to lamivudine and emtricitabine (M184V), nevirapine and efavirenze (K103N, G190S), thymidine analogs (T215F/Y and/or K219Q/E and/or D67N), and non-thymidine L nucleoside analogues).

91-97 1196
Abstract
Introduction: the analysis of genetic variants in the Republic of Crimea has so far been limited to the 2006 study. The prevalence of HIV infection on the peninsula is 20% higher than the national average, with 80% of infections associated with sexual transmission. In addition, interruptions in the supply of drugs since 2014 create the conditions for the active emergence of drug-resistant strains of HIV. Objective: to study the molecular genetic variants of HIV circulating in the Republic of Crimea in 2017–2018. Materials and methods: The work analyzes the genotype of the sequences of the HIV-1 pol gene fragment obtained from 84 infected patients observed at the Center for the Prevention and Control of AIDS of the Republic of Crimea. Results: The correlation of HIV-1 genetic variants in the studied sample reflects the molecular-epidemiological situation in Russia and Ukraine, characterized by the dominance of the A6 sub-subtype (97,6%); also revealed one sample of viruses of subtype B and recombinant form AG, unique in the sequence of the pol gene. Among the analyzed sequences from «naive» patients, there were no cases of HIV resistance. In most ART patients with treatment failure, multidrug resistance was found, with the M184V substitution leading in the frequency of occurrence, and the K103N substitution in the second most frequent. In 39 of 55 ART patients, treatment regimens were replaced due to a lack of drugs in stock.



98-102 685
Abstract
The purpose of the study is to investigate aspects of concentrations of serum markers of FAS-system of apoptosis in HIV-positive people including people with hepatitis C (HCV). Materials and methods: determination of concentration of soluble FAS receptor (sFas/APO-1/CD95) and Fas ligand (sFas-L) by enzyme-linked immunosorbent assay in HIV/HCV-co-infected patients (n=84), HIV-mono-infected persons (n=84), patients diagnosed with chronic viral hepatitis C (control group, n=64) and among notionally healthy population (control group, n=87). Results: higher levels of sFas in HIV-mono- and HIV/HCVco-infected patients in comparison with control groups (notionally healthy population and patients with chronic viral hepatitis C) were detected. Conclusion: definite aspects of levels of apoptosis serum markers testify higher risk of developing paraneoplastic syndromes in HIV-positive patients including HCV-co-infected patients.

CLINICAL AND EPIDEMIOLOGICAL RESEARCHES

103-109 810
Abstract
The purpose of this work was to study the characteristics of radiation diagnosis of surgical pathology of the spleen in patients with AIDS. Materials and methods. The work is based on the data of radiation studies of 188 AIDS patients who were hospitalized in the surgical department. The sensitivity and specificity of MSCT and MRI in this pathology were assessed. MSCT was the «gold standard» as the most accessible and informative method of radiological diagnosis of abdominal pathology with the ability to perform minimally invasive surgical procedures (external drainage under CT control). The examination program of these patients was supplemented with an abdominal MRI scan only in difficult diagnostic cases. Hepatosplenomegaly in AIDS patients is always present. Results. Heart attacks of the spleen in patients with AIDS develop on the background of severe intoxication and do not require surgical treatment. For large spleen abscesses (up to 3 cm), minimally invasive external drainage under CT control is required, if it is ineffective, a laparotomy and elimination of the pathologic focus followed by drainage of the surgical area are treated conservatively. In the case of total dissemination of the spleen, patients should perform splenectomy.



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ISSN 2077-9828 (Print)