Цель исследования: оценить влияние антиретровирусной терапии (АРВТ) на показатели спермограммы у мужчин, инфицированных ВИЧ.
Материал и методы: Проведено проспективное исследование случай-контроль у 66 мужчин с ВИЧ-инфекцией, которые обратились для оценки фертильности. 1 группу исследования составили 51 мужчина, принимающий АРВТ; 2 группу – 15 мужчин, не получавших АРВТ. Проведена оценка 97 и 25 образцов спермы соответственно. Статус пациентов по ВИЧ-инфекции оценивали на основании данных о стадии и фазе заболевания, уровне вирусной нагрузки, CD3+, CD4+ , CD8+ лимфоцитов и длительности АРВТ.
Результаты исследования: В 1 группе «стаж» ВИЧ-инфекции на момент включения в исследование был статистически значимо выше, чем во 2 группе – 5 лет (2-9 лет) и 2,5 года (0,4-4,5), соответственно, (р=0,0004). Медиана продолжительности приема препаратов в 1 группе составила 1,5 года. В группе пациентов, принимающих АРВТ, в структуре патозооспермии преобладала тератозооспермия (40%), доля патологических форм сперматозоидов в данной группе было статистически значимо выше по сравнению со 2 группой (97 (96 -98) и 96 (94,5-96,5); р=0,006). В 1 группе пациентов установлена отрицательная взаимосвязь числа аномальных сперматозоидов и уровня CD4+ лимфоцитов (r=-0,362;р=0,026), длительностью заболевания (r=0,173;р=0,173) и концентрацией сперматозоидов (r=-0,242;р=0,020), числом прогрессивно–подвижных форм категории «в» (r=-0,241;р=0,024). Длительность АРВТ отрицательно коррелировала с числом прогрессивно–подвижных сперматозоидов категории «в» (r=-0,224;р=0,036).
Во 2 группе пациентов была выявлена статистически значимая положительная взаимосвязь между уровнем СД4+ лимфоцитов, объемом эякулята (r=0,778;p=0,014) и количеством прогрессивно–подвижных сперматозоидов категории «в» (r=0,667;р=0,05). Также была обнаружена статистически значимая отрицательная взаимосвязь уровня вирусной нагрузки и объема эякулята (r =-0,669;р=0,035).
При оценке процента фрагментации ДНК сперматозоидов было выявлено, что данный показатель был выше у ВИЧ – инфицированных пациентов, принимающих АРВТ по сравнению с ВИЧ – положительными мужчинами, не использовавших терапию (15,8 % (12,4-23) и 14% (10,9-20,5); р=0,533).соответственно.
Таким образом, у ВИЧ–инфицированных пациентов, принимающих АРВТ, наблюдается патозооспермия, а именно увеличивается число патологических форм сперматозоидов, снижается их подвижность и повышается фрагментация ДНК сперматозоидов. Доля аномальных форм сперматозоидов выше при низких показателях СD4+ лимфоцитов. Концентрация сперматозоидов снижается, а количество их неподвижных форм увеличивается при длительном «стаже» ВИЧ-инфекции. У ВИЧ-положительных пациентов, не использующих АРВТ, при высоких уровнях вирусной нагрузки снижается объем эякулята и этот же параметр возрастает при увеличении уровня CD4+ лимфоцитов.
ОБЗОР И АНАЛИЗ ОТЕЧЕСТВЕННЫХ ЭПИДЕМИОЛОГИЧЕСКИХ ИССЛЕДОВАНИЙ
Epidemiology and hygiene HIV infection
ТУБЕРКУЛЕЗ И МИКОБАКТЕРИОЗЫ
The aim: to analyze the cases of mycobacteriosis in the population of people living with HIV, identified in the infectious diseases hospital in Saint-Petersburg over the past decade.
Materials and methods. 90 cases of patients with HIV and mycobacteriosis, who were treated at the clinical infectious diseases hospital named after S.P.Botkin in the period from 2005 to 2017 were analyzed. Distribution of cases by year and etiology was performed. The inclusion criteria were the presence of HIV, culturally confirmed diagnosis of mycobacteriosis. Exclusion criteria: detection of non-tuberculosis mycobacteria without species identification. Two groups were distinguished: mycobacteriosis caused by mycobacterium avium (83 patients) and mycobacteriosis caused by other non-tuberculosis mycobacteria (7 cases). The distribution of patients by sex, age, aspects of epidemiological anamnesis was performed, the main clinical forms were characterized. Sources of bacterial excretion in mycobacteriosis in patients with HIV infection were recorded.
Results. Since 2012, there has been an increase in the frequency of mycobacteriosis detection in patients with HIV: the growth of nosology over the past five years, on average, was 57% per year. Group Mycobacterium avium complex was characterized mainly by sexual path of HIV transmission (68,7%), the average age was 35 years, one third of patients were employed at the time of detection of the disease (35%). 11 persons (13,3 per cent) reported a history of being in prison, only four (4,8 per cent) were active drug users. In the group of patients with mycobacteriosis caused by other non-tuberculosis mycobacteria, the hemocontact pathway of HIV transmission prevailed (57,1%), the penitentiary history was 28,6%. In more than half of the cases, the leading source of bacterial excretion was the material of the upper respiratory tract.
Conclusion. There is a steady increase in mycobacteriosis in the structure of secondary infections in patients with HIV. The leading etiological agent was mycobacterium avium, patients with this pathology has preserved social status, sexually transmitted infection. Mainly developed generalized forms of the process, the most frequent source of bacterial excretion according to this sample was the material of the respiratory tract.
We studied social status, clinical and radiological manifestations, microbiological and immunological peculiarities in 26 latestage HIV infection patients with pulmonary TB and concomitant mycobacteriosis. They all had CD4+ lymphocyte counts less than 30 cells/μL of blood, did not receive antiretroviral therapy, and excreted both M. tuberculosis and nontuberculous mycobacteria (NTM). Identification of NTM species was based on molecular genetic methods. We found M. avium complex in 84,6%, M. kansasii — in 7,7%, M. fortuitum — in 3,8% and M. xenopi — in 3,8% of the patients. The disease manifested 6–9 years after diagnosing HIV infection; it had pronounced intoxication syndrome, bronchopulmonary and extrapulmonary presentations and was accompanied by other opportunistic infections. Radiological studies revealed intrathoracic adenopathy, dissemination with predominant localization in the middle and lower lung departments, foci and small infiltrates with cavities; injury of interlobar and visceral pleura.
Сombination of tuberculosis and viral hepatitis have been registered 2525 newly identified patients in Saint-Petersburg for the period 2006–2017. Some of these patients have been infected with HIV. Fatal outcome in 625 (24,7%) was noted. Patients with tuberculosis and chronic viral hepatitis have had a combination of viral hepatitis B and C in 36% of cases. Patients with combination tuberculosis and chronic hepatitis of unknown etiology experienced a more frequent death (60%) than patients with combination tuberculosis and other chronic viral hepatitis. In patients with concurrent tuberculosis, chronic viral hepatitis and HIV infection, patients infected viral hepatitis B and C were 31,6%. In 160 patients with fatal outcomes had a combination of infections (tuberculosis, viral hepatitis and HIV infection), the mortality rate of persons with hepatitis of unknown etiology was the lowest (42%), compared with a group of individuals affected by viral hepatitis B and C simultaneously (83%). Among patients with tuberculosis, chronic hepatitis and HIV infection, the highest incidence of tuberculosis of the intrathoracic lymph nodes and disseminated pulmonary tuberculosis was registered. Lethal outcomes most often occur in individuals with advanced tuberculosis, in whom the secretion of mycobacteria tuberculosis into the external environment has not been established. Given the high level of mortality in patients with simultaneous defeat of tuberculosis, viral hepatitis and HIV infection, it is necessary to establish their centralized registration in order to study the epidemiological patterns and clinical features of co-infections.
EPIDEMIOLOGY
The main trend of HIV epidemic development in Southern Russia is identical to Russia’s nationwide but less intense. High incidence rates are registered in such regions that have a saturated prevalence of HIV infection at the population level. During 1998–2018 an annual increase in HIV incidence has permanent vacillation ranging between +5 and +15%. This vacillation turned to be influenced by insufficient routine HIV testing coverage, which has always been lower than Russia’s nationwide rate and hardly ever reached 20% until 2017. The HIV incidence steadily biases into the age of 30–44 and elders. Sexual transmission of HIV predominates in the South since 2004. There are sustained agencies by which new HIV infections occur in Southern Russia and upward trajectory of HIV epidemic.
The aim of the study is to characterize the trends in the development of the epidemic process of HIV infection in connection with the epidemiological situation of drug addiction in the Republic of Tatarstan.
Materials and methods. The official statistical data on the incidence of HIV infection and drug addiction in the Republic of Tatarstan for the period 1987–2016, the data on the prevalence for 2001 and 2016 are analyzed.
Results. Direct correlation of the prevalence of HIV infection and prevalence of drug addiction in the different territories of the Republic of Tatarstan were identified for 2001 data (r=0,81, p<0,001) and for 2016 (r=0,82, p<0,001). A statistically significant increase in the incidence of HIV infection in the population against the background of a decrease in the incidence of drug addiction was demonstrated. In the early stages of the epidemic in the region HIV infection spread mainly through injecting drug use and, in recent years, HIV has been sexually transmitted mainly through heterosexual contact.
Conclusion. The output of infection outside the population of injecting drug users and the prevalence of sexual transmission of HIV in recent yearsare a reflection of adverse trends in the direction of generalization of the epidemic of HIV infection.
The penitentiary system is one of the leading factors in preservation and the spread of HIV infection and tuberculosis epidemics among the general population. The aim of the analytical review is to assess the trends of the HIV and tuberculosis epidemics, as monoinfections in prisons, and to evaluate their influence on the general situation in the North-West Region. In the study were used data from the Rosstat and the Ministry of Justice annual reporting forms during 2007–2017. Results. Tuberculosis incidence, prevalence and mortality in the North-West Region penitentiary system for the review period have significantly reduced, the HIV incidence and mortality rates also tend to go down, nevertheless the HIV prevalence is continuing to go up. At the same time, in either case, there is a significant excess of indicators in correctional system over similar data among the general population. Conclusion. In the North-West Region the tuberculosis situation in the penitentiary facilities is improving, the HIV situation is remaining problematic. The correctional system of the Arkhangelsk oblast, the Republics of Karelia and Komi and the Novgorod oblast have a greatest impact on the tuberculosis and HIV epidemic situation among the general population, the least influence is in the Kaliningrad oblast.
Aim: to analyze the prevalence, structure of drug resistance and drug resistance mutations in the protease and reverse transcriptase genes of HIV-1 among treatment naïve patients.
Materials and methods. We analyzed protease and reverse transcriptase sequences from 1560 treatment naïve HIV-infected patients from all Federal Districts of the Russian Federation with the first positive immune blot during 1998–2017. Sequences were analyzed for the presence of drug resistance mutations and predicted drug resistance to antiretroviral drugs using two algorithms — Stanford HIVDR Database (HIVdb) and the 2009 SDRM list (CPR).
Results. The prevalence of drug resistance mutations was 11,1%. More often the prevalence of drug resistance was found for non-nucleoside reverse transcriptase inhibitor drugs (rilpivirine, nevirapine, efavirenz). The prevalence of transmitted drug resistance associated with mutations from the SDRM list was 5,3%, which is classified by the WHO as a moderate level. However, it should be noted that since the large-scale use of antiretroviral drugs in the Russian Federation, there has been a trend towards a gradual increase in the level of the transmitted drug resistance, and in 2016 it has already reached 6,1%.
Conclusion. The results demonstrate the need for regular surveillance of the prevalence of HIV drug resistance to antiretroviral drugs among treatment naïve patients in the Russian Federation.
The aim of this study was to assess the dynamics of HIV infection detection rates among various groups of the population of the Republic of Bashkortostan in 2003–2017. Materials and methods. The statistical data of the form № 4 of the Federal state statistical observation «Data on the results of blood testing for HIV antibodies» in the Republic of Bashkortostan for the period from 2003 to 2017 were analyzed. The time interval was divided into three periods of 5 years. For each of the five-year periods, the average number of HIV testing, the number of HIV-infected people identified, the level and structure of HIV detection for different groups of the population were calculated. The average number of blood tests for antibodies to HIV common to all groups of people in 2008–2012 increased from 866 307 to 938 978 compared to 2003–2007, and then decreased to 768 143 in 2013–2017. The average indicator of the number of blood tests for HIV antibodies in the Republic of Bashkortostan was 212,4 in 2003–2007, 231,1 in 2008–2012, 188,8 per 1000 population in 2013–2017. The average number of HIV testing for men who have sex with men decreased 58 times from 232 in 2003–2007 to 45 in 2008–2012, and then to 4 in 2013–2017. The largest increase in number of HIV testing (2,3 times) was registered among foreign citizens from 12 982 testing in 2003–2007 to 29 610 in 2013–2017.
The average indicator of HIV-infected people common for all groups of the population increased 3,8 times from 736 cases in 2003–2007, to 1260 — in 2008–2012 and 2796 — in 2013–2017. The largest increase in HIV cases, in the studied period of
time, was recorded among people examined for clinical indication — 6,2 times (from 140 to 862 cases), among foreign citizens an increase of 4,3 times was registered (from 10 to 43 cases), among the population referred to the group «other» — an increase
of 4,2 times (from 111 to 469 cases). The average detection rate of HIV-infected people, common for all groups of the population increased 4,4 times, in 2003–2007 it averaged 81,8, in 2013–2017 — 356,9 per 100 000 testing. The highest increase of detection of HIV infection was registered among prisoners from 299,5 to 2644,0 per 100 000 testing (8,8 times), among the people examined for clinical indications from 68,6 to 409,1 (6,0 times), among drug addicts — from 805,9 to 4356,4 (5,4 times), among the population referred to the group «other» — from 45,4 to 244,5 (5,4 times). In the structure of HIV detection during the study period there were also changes, the average percentage of the group examined on clinical indications increased significantly from 19,69±1,49% in 2003–2007 to 32,16±0,90%, in 2013–2017, this category was in the first place in the structure among all population groups. There was an increase in the average percentage of the population referred to the group «other» from 15,61±1,36% to 17,50±0,73%, this category occupied the second place in the structure. In the structure of HIV detection, the average percentage of pregnant women decreased significantly from 11,39±1,19% to 6,60±0,48%. The study of the dynamics of indicators of detectability of HIV infection among various groups of the population allows us to determine the trends in the spread of the disease in society, which further makes it possible to apply the data in the development of preventive measures
Aim: to analyze the prevalence, structure of drug resistance and drug resistance mutations in the protease and reverse transcriptase genes of HIV-1 among treatment naïve patients.
Materials and methods. We analyzed protease and reverse transcriptase sequences from 1560 treatment naïve HIV-infected patients from all Federal Districts of the Russian Federation with the first positive immune blot during 1998–2017. Sequences were analyzed for the presence of drug resistance mutations and predicted drug resistance to antiretroviral drugs using two algorithms — Stanford HIVDR Database (HIVdb) and the 2009 SDRM list (CPR).
Results. The prevalence of drug resistance mutations was 11,1%. More often the prevalence of drug resistance was found for non-nucleoside reverse transcriptase inhibitor drugs (rilpivirine, nevirapine, efavirenz). The prevalence of transmitted drug resistance associated with mutations from the SDRM list was 5,3%, which is classified by the WHO as a moderate level. However, it should be noted that since the large-scale use of antiretroviral drugs in the Russian Federation, there has been a trend towards a gradual increase in the level of the transmitted drug resistance, and in 2016 it has already reached 6,1%.
Conclusion. The results demonstrate the need for regular surveillance of the prevalence of HIV drug resistance to antiretroviral drugs among treatment naïve patients in the Russian Federation.
CLINICAL PRACTICE
The goal of the study was to evaluate the impact of antiretroviral therapy (ART) on the semen characteristics in HIV-infected men.
Materials and methods. A prospective case-control study enrolled 66 HIV-infected male patients who presented for fertility assessment. Group 1 included 51 male patients treated with ART; Group 2 included 15 males who were not receiving ART. 97 and 25 semen samples were analyzed, respectively. HIV status was assessed based on the data regarding the stage and phase of the disease, viral load, CD3+, CD4+, CD8+ counts and the ART duration.
Study results. At enrollment in the study, the duration of HIV infection in Group 1 was longer than that in Group 2 (the difference being statistically significant): 5 years (2–9 years) versus 2,5 years (0,4–4,5), respectively (р=0,0004). Median duration of treatment in Group 1 was 1,5 years. The most common type of abnormal semen morphology in ART-treated patients was teratozoospermia (40%), and the percentage of abnormally shaped spermatozoa in this group was higher compared to Group 2 (the difference being statistically significant): 97 (96–98) versus 96 (94,5–96,5); р=0,006). Group 1 demonstrated a negative relationship between the count of abnormally shaped spermatozoa and CD4+ cell count (r=–0,362; р=0,026), disease duration (r=0,173; р=0,173) and sperm count (r=–0,242; р=0,020), progressively motile (category B) sperm count (r=–0,241; р=0,024). The ART duration showed an inverse correlation with the progressively motile sperm count (category B) (r=–0,224; р=0,036). Group 2 demonstrated a statistically significant positive relationship between the CD4+ cell count, the semen volume (r=0,778; p=0,014), and the count of progressively motile (category B) spermatozoa (r=0,667; р=0,05). We also revealed a statistically significant inverse relationship between the viral load and the semen volume (r=–0,669; р=0,035). Sperm DNA fragmentation was found to be higher in HIV-infected patients treated with ART compared to HIV-infected men not receiving ART (15,8% (12,4–23,0) and 14% (10,9–20,5); р=0,533), respectively. Thus, HIV-infected patients treated with ART demonstrated abnormal sperm morphology (increased abnormal sperm count), decreased sperm motility and increased sperm DNA fragmentation level. The percentage of abnormally shaped sperm was higher in patients with lower CD4+ cell counts. In patients with a long history of HIV infection, the sperm count decreases and the count of immotile spermatozoa increases. HIV-infected individuals who are not receiving ART and have high viral loads show decreased semen volume. This value increases upon an increase in the CD4+ cell count.
The aim of the work was to compare the five most widely used ELISA diagnostic kits on the territory of the Russian Federation, which are used for screening for HIV infection.
Materials and methods. 5442 samples from visitors of diagnostic centers who came for blood donation for non-infectious analyses, cohorts with a high risk of HIV infection, as well as patients with potentially interfering conditions were used as a material for the study. Additionally, seroconversion panels and a panel of viral diversity were used to evaluate the analytical characteristics. The following test systems were compared: Architect HIV Ag/Ab Combo (Abbott), Genscreen Ultra HIV Ag-Ab (Bio-Rad), CombiBest HIV-1,2 AG/AT (Vector-Best), DS-ELISA-HIVAGAT-SCREEN (Diagnostic Systems), HIV-1,2-AG/AT (Medical-Biological Union).
Conclusion. The diagnostic sensitivity of all tests was 100% with the exception of one (Medical-Biological Union), in which it turned out to be 99,54%. Diagnostic specificity ranged from 99,58% to 99,89%, but unexpectedly strongly depended on the test population, decreasing on a group with a high risk of HIV infection to 93,26% (Vector-Best). The convergence between initial and repeat reactive samples ranged from 100% (Abbott) to 89,51% (Vector-Best). The results of the analysis of seroconversion panels showed that the tests differed slightly from each other, receiving positive results from 22,12% (Diagnostic Systems) to 27,88% (Abbott) samples. When testing the panel of viral diversity, diagnostic tests from foreign manufacturers showed better results, revealing 100% (Abbott) and 85,9% (Bio-Rad). The smallest number of panel samples was detected by the kit of the Medical-Biological Union (52,1%). This work is the only study where the 4th generation ELISA kits, widely used in the Russian Federation for screening for HIV infection, were compared in an extensive sampling. The results obtained make it possible to evaluate the effectiveness of the use of the listed kits in routine diagnostic practice.