HIV infection, secondary conditions and comorbidities. Part 1: Epidemiology and the basis of the problem

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  • Authors: Belyakov N.A.1,2,3, Rassokhin V.V.1,2,3, Stepanova E.V.1,4, Leonova O.N.1,4, Boeva E.V.1,2
  • Affiliations:
    1. Pavlov First Saint Petersburg State Medical University
    2. Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology
    3. Institute of Experimental Medicine
    4. Saint Petersburg Centre for Prevention and Control of AIDS and Infectious Diseases
  • Issue: Vol 18, No 4 (2018)
  • Pages: 7-16
  • Section: Articles
  • URL: https://journals.eco-vector.com/MAJ/article/view/11680
  • DOI: https://doi.org/10.17816/MAJ1847-16
  • Cite item

Abstract


An analysis of the human immunodeficiency virus (HIV) epidemic’s trajectory with priority-setting taking into account HIV-associated comorbidities for each time period was performed. A classification of comorbid diseases and conditions in HIV infection by cause and setting of their occurrence is presented. Opportunistic infections and secondary diseases that remain some of the leading causes of severe complications and mortality are characterized. The difficulty of the development of immune reconstitution inflammatory syndrome against the background of late diagnosis of HIV infection and initiation of antiretroviral therapy is highlighted.


Full Text

Background

Comorbidities are characteristic of many chronic pathologic processes, especially at mature and old age. For a number of reasons, human immunodeficiency virus (HIV) infection in a combination with other infectious and non-communicable diseases holds a special place in shaping these comorbid conditions. It is to be noted that simultaneous occurrence of concomitant pathologic processes, diseases and conditions has its own specific patterns and manifestations; they may occur at a different rate, have more or less apparent clinical manifestation. In presence of concurrent illnesses associated with HIV infection, the leading role is played by the human immunodeficiency virus (HIV) that triggers the inflammatory process casing immunosuppression [1–5].

Trajectory of the epidemic and comorbidities

By and large, changes in the epidemic process depend on peculiar features of HIV infection per se, i.e., general general epidemic situation in a region, modes of the virus transmission, prevailing populations involved in the process and other factors as well of an infected patient — state of his/her health at the moment of infection, age, gender, disease duration, living conditions and social environment, pernicious habits and addiction, etc. [6].

Table 1 presents the most common combinations of diseases in the setting of HIV infection during various periods of the epidemic.

 

Table 1. Evolution of comorbidities during the HIV epidemic in the Russian Federation

Combination of diseases

Periods of time

Predominant transmission modes

Mono-infection: HIV

80–90s of the 20th century

Heterosexual and homosexual

Co-morbidity: HIV + IDU

Turn of the 20th and 21st centuries

Parenteral

Triple morbidity: HIV + IDU + CVHC

Beginning of the 21st century

Parenteral and sexual

Multiple morbidity: HIV + IDU + CVHC + OIs

Beginning of the 21st century

Parenteral and sexual

Multiple morbidity: HIV + CVHC + OIs + TB

10s of the 21st century

Sexual and parenteral

Multiple morbidity: HIV + CVHC + OIs + TB + somatic and neurological conditions

Late 10s of the XXI century

Sexual and parenteral + additional factor — aging

Note. IDU — injecting drug use, CHCV — chronic viral hepatitis C, OIs — opportunistic infections, TB — tuberculosis.

 

In Eastern Europe and Central Asia, due to a significant social, economic and political turmoil, the local conditions i.e. injecting drug usage, HIV infection, viral hepatitis C (HCV) and tuberculosis favoured the fusion of four epidemics. Previously, such a combination of epidemics has never occurred in other geographic areas to its full extent [7].

During the initial period, back in the 1980s, the HIV epidemic in the Russian Federation (RF) affected, mostly, the socially disadvantaged strata of society and then penetrated into the general population [8].

This period of HIV as mono-infection in the RF lasted only for several years in the early 1990s. Later on, the social, economic and epidemic situation changed, and several new factors influencing on the occurrence of HIV comorbidities appeared:

— injectable drugs became widely available, and drug usage as an entry point for HIV infection proliferated in society [9];

— parenteral transmission became predominant causing the spread of viral hepatitis among HIV-infected drug users [7, 10];

— severe immunodeficiency lead to the spread of tuberculosis among that population of patients, which overlapped with other comorbidities such as drug addiction, alcoholism, chronic viral hepatitis B and C (CVHC) [11, 12];

— opportunistic infections and HIV-associated cancers as well as AIDS-related processes occurred as immunosuppression progressed [8];

— in the recent years, while people living with HIV (PLHIV) grew old and now have a long history of infection, some pronounced somatic and neuropsychiatric disorders become visible, affecting negatively the life expectancy and the quality of life as well as reducing chances for employment [13].

As a result, two decades past the beginning of the epidemic, many patients developed comorbidities that required an intervention of various professionals, such as infectiologists, phthisiatricians, oncologists, addiction psychiatrists, neurologists, internists and others.

The experience gained and analysis of major combinations of diseases allowed us to systematize comorbidities and present this systematization as a working classification that is supposed to better reflect a patient’s condition over time and to optimize a comprehensive care in the future (Figure 1).

 

Fig. 1. HIV-associated comorbid diseases and conditions. IDU — injection drug usage; HIV — human immunodeficiency virus; DM — diabetes mellitus; AIDs — autoimmune diseases

 

Table 2 shows the most common sequelae of direct and indirect HIV impact on the human body.

 

Table 2. Classification of HIV comorbid diseases and conditions, by cause and setting of their occurrence (Belyakov N.A., 2016)

1. Diseases that the individual had prior to acquiring HIV (preexisting)

– Congenital and genetic anomalies

– Acquired conditions of organs and systems regardless of their pathogenesis present at baseline

– Psychiatric and deviant disorders

– Substance dependence, including drug and alcohol abuse, smoking, etc.

– Other conditions capable of modifying typical course of HIV infection

2. Those resulted from HIV-associated immunosuppression and concurrent infections

– Opportunistic infections

– Tuberculosis and mycobacteriosis

– Cancers

– Purulent-septic conditions with various etiology

– Chronic hepatitis with various etiology

– STIs

– Other conditions due to immunosuppression

3. Non-communicable diseases potentiated by chronic HIV-related inflammation (indirect effect of HIV)

– Osteoporosis

– Atherosclerosis

– Nephropathy

– Autoimmune diseases

– Metabolic syndrome

– Diabetes mellitus

– Arthrosis and arthritis

– Other illnesses

4. Diseases and syndromes due to the direct effect of HIV on the organs and systems

– HIV encephalopathy

– HIV polyneuropathy

– HIV-associated neurocognitive disorder (HAND)

– Lymphadenopathy

– Enteropathy

– Wasting syndrome

– Other manifestations and syndromes

5. Diseases and syndromes due to ART, therapy of comorbidities

– Toxic impairment

– Metabolic disorders, secondary conditions

– Drug adverse events

– Sequelae of drug-drug interactions

– Other

Note. ART — antiretroviral therapy, STIs — sexually transmitted infections.

 

The first group is represented by such diseases and conditions that preceded HIV infection and, in a number of cases, facilitated its acquisition through deviant behaviors that put people at high risk of HIV infection. This could include baseline psychological disorders and mental illnesses, drug addiction, alcoholism and others [14–17]. In turn, congenital and genetically determined diseases as well as previously acquired somatic and systemic pathologic conditions became aggravated by HIV infection and precluded patients from being adhered to antiretroviral therapy (ART) [17].

The second group consists of either continuation of HIV-associated immunosuppression or concurrent infections. Comorbidities falling into this category are the major contributors (3/4) to HIV-related mortality [2].

The third group of comorbidities comprising disorders of organs and organ systems is the consequence of potentiating and cumulative effect of chronic inflammation caused by HIV. These diseases manifest as patients live longer and age with HIV [18].

The fourth group of comorbidities is related to the direct impact of HIV on CD4 in the blood T lymphocytes and other cells that have receptors for the virus and co-receptors localized in certain organs and tissues (gastrointestinal [GI] tract), central nervous system (CNS), lymphoid tissue, and others [19]. These pathologic manifestations from a part of various organs lead to significant reduction of the quality of life and life expectancy and also to premature disability of individuals living with HIV [18].

The fifth group includes diseases, syndromes and conditions that can be iatrogenic, since they are caused by medications used in the regimens of antiretroviral therapy or those prescribed to treat concurrent communicable and non-communicable diseases, such as toxic impairment, metabolic disorders, secondary conditions, sequelae of drug-drug interactions, other untoward side effects of drugs.

Nevertheless, not all the consequences of HIV infection are irreversible, that is why HIV care as opposed to general healthcare is a balance between etiotropic and pathogenetic therapy, intensive care, symptomatic treatment of chronic symptoms and signs, as well as palliative care. Trajectory of HIV disease is somewhat multiform and unpredictable with a wide range of possible complications, different rates of disease progression and varying life expectancy. Nowadays, people with HIV live longer, which entails certain challenges, and a thorough revision of the problem of comorbidity in HIV-infected patients is needed, taking into account the context of their somatic disease and comorbidity treatment.

Opportunistic infections (OIs)

Given the recent rate of HIV-related mortality, the profile of the most dangerous comorbidities looks as follows: tuberculosis, neuropsychiatric disorders and somatic illnesses. Drug addiction along with concomitant psychiatric problems are the basis for other comorbidities due to behavioral deviations and lack of adherence to follow-up and treatment [9, 10]. Drug abuse significantly aggravates a disease manifestation and contributes to multiple morbidity including HIV, HCV, tuberculosis, which makes the situation more dramatic and less reversible [11, 12].

Despite the use of ART and chemoprophylaxis, opportunistic infections remain a serious challenge for HIV-infected patients and the leading cause of morbidity and mortality [20]. OIs are divided into bacterial, fungal, viral and protozoan infections; many of these OIs and HIV potentiate each other leading to a disease progression and proliferation [21–24].

OIs may occur in early stages of HIV infection as well as at the acquired immune deficiency syndrome (AIDS) stage because of increasing incompetence of the immune system causing severe CNS lesions and malignant neoplasms that disseminate and proliferate [23]. A universal method of preventing secondary conditions is timely initiated ART.

Among the opportunistic conditions the most common are tuberculosis (46%); visceral candidiasis (20%); cryptococcosis (6.4%); cerebral toxoplasmosis (5.2%); Pneumocystis pneumonia (5%); cancers (4%); Cytomegalovirus (CMV) (3%) [24].

Candidiasis is encountered in 70-80% of HIV-infected patients. At early stages, superficial candidiasis prevails i.e. oropharyngeal candidiasis; candidal vulvovaginitis, persistent with frequent recurrence or poorly responding to treatment; cutaneous candidiasis. Invasive visceral candidiasis (candidiasis of bronchi, trachea or lungs), esophageal candidiasis occurs more frequently when the CD4 cell count in blood is below 200 cell/µL [25]. Disseminated candidiasis causes death in 1.2% of patients on average, [26, 27].

As HIV infection progresses, cryptococcal infection becomes disseminated. Most often, this disease occurs when the CD4 cell count in blood drops below 50 cell/µL; it manifests as meningoencephalitis or cryptococcal sepsis involving various organs and organ systems (invasive mycosis). In the mortality profile, meningitis accounts for 3.6% [23].

Pneumocystis pneumonia (PCP) also belongs to mycotic infections. The major clinical symptom is lung impairment that entails respiratory failure. The PCP rate does not decline [8, 28] accounting for 21.7% of lethal outcomes. Primary chemoprophylaxis of Pneumocystis pneumonia with Trimethoprim/sulfamethoxazole (TMP/SMX) is indicated if CD4 in blood is 200 cell/µL or less.

Cerebral toxoplasmosis is the main type of protozoan infections [8, 29]. In the setting of AIDS, toxoplasmosis infrequently becomes disseminated, affecting lungs, eyes, lymph nodes, liver and other organs; the diagnosis may be a hard task. Clinical manifestations of toxoplasmosis in patients with HIV infection are seen when CD4 in blood drops below 100 cell/µL. That is why the patients are receiving primary chemoprophylaxis with TMP/SMX. The mortality is 8.4% on average [25, 26]. A typical, but not specific feature of toxoplasmosis is brain damage with perifocal edema localized in the frontal lobes and in the basal ganglia, manifested as multiple lesions and ring formation [25].

Among viral infections the herpesviruses, the first and the foremost CMV, play a pivotal role [8, 25]. This disseminated condition affects the brain (encephaloventriculitis), lungs, bone marrow, adrenal glands, kidneys, liver, GI tract and eyes. Lethality of CMV infection remained the same for several years at 4.2% on average [24, 26]. Progressive systemic CMV vasculitis plays a leading role in extensive visceral disease [30]. The chances of being infected with CMV are especially high in patients with the CD4 cell count less than 50 cells/µL. When CD4 drops below 100 cell/µL and the CMV DNA is detected in blood, a prophylactic treatment of CMV disease is recommended [27].

Illnesses caused by other herpesviruses include Herpes simplex virus 1 and 2; Varicella-zoster virus, type 3; Epstein-Barr virus (EBV), or Human herpes virus 4; types 6, 7 and 8 [8, 22, 25]. At early stages of HIV infection, Herpes simplex virus may cause superficial lesions of the skin and mucous membranes with no recurrence. However, when immunodeficiency grows progressesively worse (CD4 count drops below 200 cell/µL), the same virus becomes implicated in frequently recurrent dermal and mucosal lesions and longstanding unhealing ulcers. It also inflicts damage on CNS, GI tract, lungs and provokes disseminated forms of the disease.

In the setting of profound immunodeficiency, herpesvirus 3 causes similar severe dermal and mucosal lesions, recurrent ganglionitis as well as visceral and disseminated forms.

In the clinical settings, EBV-related diseases are as follows: Burkitt lymphoma; nasopharyngeal carcinoma; leukoplakia; B-cell lymphoma; CNS impairment (meningoencephalitis, polyradiculoneuritis).

Progressive multifocal leukoencephalopathy (PML) caused by the JC virus is a CNS demyelinating disease affecting the white matter of the brain hemispheres which usually occurs when CD4 count drops below 100 cells/µL [31]. This disease accounts for 5.4% of deaths [24, 26]. The major prophylactic and therapeutic modality is an early initiation of ART with the maximum penetration into the CNS.

Making a diagnosis of brain impairment that may have multiple etiologies, such as toxoplasmosis, CMV infection, PML, lymphoma and others, is a difficult task. The analysis of 4,693 cases when patients with HIV infection were treated at the inpatient setting of the Saint Petersburg AIDS Center in 2010–2014 shows that 22% of them had various CNS disorders e.g. tuberculous meningoencephalitis (31.3%), cerebral toxoplasmosis (31%), HIV encephalitis (21%), CMV infection (7.3%), cryptococcal meningitis (5.5%), progressive multifocal leukoencephalopathy (0.9%) and others [24, 26, 32].

Occurrence of opportunistic infections and secondary conditions depends on how well the immune system performs. When the CD4 cell count varies between 500 and 200 cell/µL, bacterial pneumonias, oral candidiasis, herpetic infections caused by the Herpes simplex virus, pulmonary tuberculosis, Kaposi’s sarcoma (localized) mostly occur. When the CD4 cell count is below 200 cell/µL PCP, the disseminated herpetic infection, Candida esophagitis, extrapulmonary and disseminated tuberculosis, toxoplasmosis, cryptococcosis, cervical cancer, lymphomas are encountered, whereas when it is less than 50 cell/µL the disseminated CMV infection, atypical mycobacteriosis, cryptosporidiosis and PML are most common.

Tuberculosis

In recent years there has been a downward trend in the incidence and prevalence of tuberculosis in the general population of Russia. At the same time annual monitoring aimed at identification of tuberculosis/HIV co-infection shows the steady increase in both the crude number of cases and the proportion of this co-infection in the morbidity profile [33]. In the majority of the regions of Russia 25 to 45% of all new cases of tuberculosis are associated with HIV infection. Thus, in the upcoming years, we should anticipate aggravation of the epidemiological situation as far as tuberculosis is concerned, which is stipulated by the unfavorable situation with co-infection [8, 34].

Occurrence of tuberculosis in the setting of immunosuppression modifies the infection course i.e. this otherwise slowly progressing disease limited to the thoracic involvement, becomes a rapidly advancing inflammatory process with an early dissemination and high rates of associated mortality. Over 70% of tuberculosis cases are diagnosed at the late stages; in recent years, cases of tuberculosis sepsis characterized by very aggressive course and dismal outcome were reported [35].

It should be noted that one of the most important problems of HIV-associated tuberculosis is the spread of drug-resistant strains of Mycobacterium tuberculosis reported in the population of patients with co-infection at the rate of 65–70%, which exceeds that in tuberculosis patients without immunodeficiency 1.5–2 times. This factor in a combination with the widespread use of ART in co-infected patients leads, on the one hand, to the reduction in mortality and, on the other hand, to the increase in a proportion of patients with chronic tuberculosis who become the epidemiological reservoir supporting disease persistence in the population of drug-dependent patients with HIV infection.

Currently, tuberculosis causes death in patients with HIV infection more frequently than other secondary and concurrent diseases [26]. The existing epidemiological situation regarding tuberculosis is influenced upon by not only clinical aspects of this disease, but also by the fact that organizational issues related to diagnosis and treatment of patients with co-infection still await their solution. Thus, the approaches traditionally used in phthisiatric practice for diagnosing a tuberculosis case cannot be applied to the population of patients with HIV infection due to peculiarities of the clinical course and the types of tuberculosis in the setting of immunosuppression. The approaches to the therapy of tuberculosis in HIV infection are significantly different from the strategy of tuberculosis treatment as a single-agent infection.

Immune reconstitution inflammatory syndrome in HIV infection

In most HIV-infected patients, ART initiation leads to inhibition of viral replication, an increase in the number of CD4 T lymphocytes and a recovery of the protective function of the immune system. However, not infrequently it can lead to a patient’s progressive deterioration with the emergence of new or previously treated OIs, secondary and somatic disorders [36]. Rates of immune reconstitution inflammatory syndrome (IRIS) in the patients who began to receive ART are 10–32%. Major risk factors of this syndrome include: the history of an OI on ART initiation and the low CD4 cell count (below 50 cell/µL) at baseline, a high content of HIV RNA in the blood (over lg10 5). It was noted, however, that IRIS may occur despite higher CD4 cell counts. It means that not only low CD4, but also the nonoptimal functional state of the immune system of HIV-infected patients triggers a manifestation of this syndrome. A genetic predisposition to IRIS in patients with HIV infection and tuberculosis cannot be excluded. This syndrome is more common in men, young adults and naive patients. ART regimens comprising certain drug classes are considered risk factors. [37]. Immunopathogenesis of the syndrome is not fully understood and requires further research [38]. Major constituents of IRIS are presented in Figure 2.

 

Fig. 2. Pathogenesis of immune reconstitution inflammatory syndrome. ART — antiretroviral therapy, HIV — human immunodeficiency virus, IL — interleukin, IFN — interferon, RNA — ribonucleic acid, TNF — tumor necrosis factor

 

IRIS on ART is related to activation of mycobacterial, viral, fungal and parasitic OIs. The response of the immune system may be directed against not only viable or non-viable pathogens, but also against the residual antigens. There are two options of IRIS manifestation:

  1. An inflammatory response to a latent disease that was clinically insignificant till after ART initiation;
  2. After ART initiation, ‘paradoxical’ exacerbation of a disease that was diagnosed and treated earlier.

It should be kept in mind that an alternative reason for opportunistic infections and a patient’s deterioration may be the poor adherence to ART and/or drug resistance.

Infection with Mycobacterium tuberculosis is the most common cause of IRIS (8–50%). Most cases of tuberculosis associated with IRIS are observed during the first two to three weeks from ART initiation; clinically it is accompanied by deterioration of the patient or new clinical and radiological symptoms such as fever, lymph node enlargement and fresh infiltration. Currently, it is recommended to add ART in patients with CD4 counts below 200 cell/µL two to eight weeks after initiating the treatment of tuberculosis [39].

In patients with the baseline CD4 cell count less than 100 cell/µL the rate of IRIS associated with Mycobacterium avium complex (MAC) is about 3.5%. As a rule, MAC-associated IRIS occurs in patients with pronounced immunosuppression. Clinically, this syndrome manifests during the first two to eight weeks after ART initiation as fever and enlarged and painful lymph nodes (69%) [40].

Individuals with Cryptococcus-related IRIS may present with meningitis, lymphadenitis, pneumonitis and localized abscesses. IRIS with CNS involvement is diagnosed in 1.5% of patients with CD4 below 200 cell/µL who started receiving ART. As a rule, it manifests in a paradoxical form. Approximately 60% of IRIS cases begin after the first month of effective ART [41].

PCP is one of the most common OIs in HIV-infected patients. Usually, deterioration takes place during the first two to three weeks from ART initiation and is manifested by recurrent fever, increasing hypoxia and fresh pulmonary infiltrates on a chest radiograph [42].

Herpes simplex virus and activation of Human papillomavirus (HPV) often present themselves as the IRIS manifestation. Not infrequently, retinitis, vitreitis and uveitis of CMV origin are diagnosed in the presence of IRIS. Cases of PML with the latent or paradoxical course related to ART initiation are reported [24].

The possibility of aggravating any tumorous process in the brain due to ART initiation cannot be excluded. Some recent studies showed that IRIS could transitorily increase a risk of Kaposi’s sarcoma and non-Hodgkin’s lymphomas in HIV-infected patients, and timely initiation of ART is the best strategy to prevent these malignancies [43].

In some patients initiated on ART such autoimmune conditions as Graves’ disease and sarcoidosis may present as IRIS manifestations [37].

A timely prescribing of ART is crucial for prevention of IRIS. In order to identify latent and subclinical forms of OIs before initiating ART, patients should undergo thorough examination. Also, it is advisable to identify timely the patients with a higher risk of IRIS, to determine the best time for ART prescription and initiation in patients who already have OIs. An important component of managing patients with IRIS is the optimal approach to treatment of opportunistic infections. In case of the mild syndrome nonsteroidal anti-inflammatory drugs may be prescribed; in more severe cases glucocorticoids should be chosen [25, 37].

Sometimes IRIS requires discontinuation of ART. Its outcome strongly depends on the balance between ART initiation and the treatment of secondary conditions, including the maintenance therapy. IRIS has a favorable prognosis provided that the syndrome is diagnosed early and a correct treatment for OIs and comorbidities is provided.

Conclusion

The HIV epidemic has acquired the form of severe and comorbid conditions. Several stages of comorbidity development have been identified since the 90s of the 20th century when HIV entered in the environment of IDU infected HCV. A few years later the HIV infection passed into the stage of clinical manifestations with the addition of opportunistic and AIDS-indicator diseases. With the ageing of the epidemic a premature damage of somatic and psycho-neurological organs and systems has developed. The proposed classification of the most common comorbid conditions is noted, including the dominant role of tuberculosis, which came out on the leading position in morbidity of PLHIV. Late detection and initiation of ART in HIV-infected patients caused the development of IRIS, which is accompanied by high mortality in the RF. The pathogenesis and diagnosis of IRIS are complicated and ambiguous; as a result this diagnosis is often omitted in the clinical practice.

Acknowledgments

The authors express their sincere gratitude to their colleagues and staff who contributed to this multiyear research.

The list of abbreviations

AIDs — autoimmune diseases

AIDS — acquired immunodeficiency syndrome

ART — antiretroviral therapy

CHCV — chronic viral hepatitis C

CMV — Cytomegalovirus

CNS — central nervous system

CVHC — chronic viral hepatitis C

DM — diabetes mellitus

EBV — Epstein-Barr virus

GI — gastrointestinal tract

HAND — HIV-associated neurocognitive disorder

HCV — viral hepatitis C

HIV — human immunodeficiency virus

HPV — human papillomavirus

IDU — injecting drug usage

IRIS — immune reconstitution inflammatory syndrome

MAC — mycobacterium avium complex

OIs — opportunistic infections

PCP — pneumocystis pneumonia

PML — progressive multifocal leukoencephalopathy

RF — Russian Federation

PLHIV — people living with HIV

RNA — ribonucleic acid

TB — tuberculosis

TMP/SMX — Trimethoprim/sulfamethoxazole

About the authors

Nikolay A. Belyakov

Pavlov First Saint Petersburg State Medical University; Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology; Institute of Experimental Medicine

Author for correspondence.
Email: ras-doc@mail.ru

Russian Federation, 6/8, Lva Tolstogo street, St. Petersburg, 197089; 14, Mira street, Saint Petersburg, 197101; 12, Academic Pavlov street, Saint-Petersburg, 197376

MD, PhD, Professor, Academician of the Russian Academy of Sciences, Head of the Department of Socially Significant Infections; Head of the North-Western District AIDS Prevention and Control Center; Head of the Department of Socially Significant Infections

Vadim V. Rassokhin

Pavlov First Saint Petersburg State Medical University; Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology; Institute of Experimental Medicine

Email: ras-doc@mail.ru

Russian Federation, 6/8, Lva Tolstogo street, St. Petersburg, 197089; 14, Mira street, Saint Petersburg, 197101; 12, Academic Pavlov street, Saint-Petersburg, 197376

MD, PhD, Professor of the Department of Socially Significant Infections; Leading research associate; Head of the Laboratory of Chronic Viral Infections, Department of Ecological Physiology

Elena V. Stepanova

Pavlov First Saint Petersburg State Medical University; Saint Petersburg Centre for Prevention and Control of AIDS and Infectious Diseases

Email: boeva@gmail.com

Russian Federation, 6/8, Lva Tolstogo street, St. Petersburg, 197089; 179a, Obvodny Canal Embankment, St. Petersburg, 190103

Professor, Department of Socially Significant Infections; MD, PhD, Deputy Chief Medical Officer

Olga N. Leonova

Pavlov First Saint Petersburg State Medical University; Saint Petersburg Centre for Prevention and Control of AIDS and Infectious Diseases

Email: boeva@gmail.com

Russian Federation, 6/8, Lva Tolstogo street, St. Petersburg, 197089; 179a, Obvodny Canal Embankment, St. Petersburg, 190103

MD, PhD, Associate Professor of the Department of Socially Significant Infections; Head of the Saint Petersburg Center for Prevention and Control of AIDS and Infectious Diseases

Ekaterina V. Boeva

Pavlov First Saint Petersburg State Medical University; Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology

Email: boeva@gmail.com

Russian Federation, 6/8, Lva Tolstogo street, St. Petersburg, 197089; 14, Mira street, Saint Petersburg, 197101

Assistant of the Department of socially significant infections; Head of the Department of Chronic Viral Infection

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Supplementary files

Supplementary Files Action
1.
Fig. 1. HIV-associated comorbid diseases and conditions. IDU — injection drug usage; HIV — human immunodeficiency virus; DM — diabetes mellitus; AIDs — autoimmune diseases

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2.
Fig. 2. Pathogenesis of immune reconstitution inflammatory syndrome. ART — antiretroviral therapy, HIV — human immunodeficiency virus, IL — interleukin, IFN — interferon, RNA — ribonucleic acid, TNF — tumor necrosis factor

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