Pneumonia as a cause of death in HIV-infected patients admitted to the intensive care unit

Introduction

According to the criteria adopted in Russia (Order of the Ministry of Health and Social Development of Russia dated March 17, 2006, No. 166), a case of AIDS is registered if the patient is diagnosed with at least one of the indicator diseases, including recurrent pneumonia (2 or more episodes within 1 year)¹. At the same time, the physician faces a practical difficulty regarding whether the community-acquired pneumonia (CAP) is a secondary disease. How to determine the stage of HIV infection if an HIV-infected patient has a single episode of pneumonia that proceeds aggressively with the development of complications in the absence of other AIDS-indicating diseases? According to literature data, the incidence of single pneumonia cases in HIV-infected patients may amount to 85.9% [1], and the proportion of hospital mortality in CAP in patients with HIV infection may reach 35% [2–4]. It should be noted that the clinical guidelines of the Russian Ministry of Health “Community-Acquired Pneumonia in Adults” of 2023 and “HIV Infection in Adults” of 2020 do not contain an algorithm for managing HIV-infected patients with CAP^{2 3}.

The existing duality in the assessment of the nature of pneumonia can lead to a false interpretation of the clinical diagnosis. This examination describes a clinical situation in which CAP can be presented as recurrent only from a formal point of view, but the nature of its course clearly indicates the presence of an immunodeficiency state in a patient with HIV infection.

Description of a clinical case

Male D., 41, was admitted to the hospital with complaints of fever, weakness, and dry, obsessive cough. Diagnosis upon admission: “Coronavirus infection caused by the COVID-19 virus, the virus has not been identified”. According to oral information provided by the patient, he considered himself ill for about a week, when he noted an increase in temperature to 39.0 °C, weakness, and muscle pain. In the following days, the fever persisted. He was examined by the primary care physician in the clinic at his place of residence, received umifenovir and levofloxacin at a dosage of 500 mg 2 times a day, but the therapy was ineffective. On the 9th day of illness, due to increasing weakness, persistent fever, persistent cough, and lack of effect from therapy, he called an ambulance. The performed CT scan of the chest organs showed CT-1 state. The patient was hospitalized. The anamnesis revealed that HIV infection had been present since 2015, he was registered at the AIDS center, and took ART according to the scheme: lamivudine, tenofovir, and lopinavir/ritonavir. Chronic diseases included viral hepatitis C. He was an injection drug user. There was no data on previous pneumonia.

On admission, the patient’s condition was moderate, consciousness was clear, and the NEWS2 scale score was 6. On auscultation, breathing was weakened without wheezing; saturation was 94% on atmospheric oxygen. On admission, the hemogram showed leukopenia (leukocytes 1.9×10^9/l, lymphocytes 0.78×10^9/l, neutrophils 0.9×10^9/l) and thrombocytopenia (platelets 108×10^9/l). The C-reactive protein level was 14.50 mg/l; procalcitonin was 0.50 ng/ml. The biochemical blood test, coagulogram, and general urine analysis were without significant deviations from the norm. The number of CD4 lymphocytes was 137 cells/μl. Laboratory confirmation of COVID-19 was not received. More specifically, SARS-CoV-2 RNA was not detected by PCR in a nasopharyngeal swab twice with an interval of 4 days; IgM antibodies to SARS-CoV-2 were at the level of 0.2; IgG class was 158.58. Echo-CG was without any special features; ultrasound of the abdominal organs did not reveal any structural changes. Etiotropic therapy with favipiravir, ceftriaxone, and mofloxacin in standard therapeutic doses, along with symptomatic and pathogenetic therapies, was carried out in relation to the patient. Against the background of the therapy, the patient’s condition improved; leucopenia, thrombocytopenia, and increased concentration of C-reactive protein were stopped. On the 6th day of hospitalization (15th day of illness), the patient was discharged with improvement for further treatment on an outpatient basis.

The next day, the patient’s condition aggravated sharply: general weakness increased, chest pain and shortness of breath appeared, and body temperature rose to 39 °C. The patient was admitted to the intensive care unit in serious condition. The severity of the condition was stipulated by respiratory failure of the 1st–2nd degree. According to the physical examination data at the time of admission, body weight was lower than normal, consciousness was clear; the patient was comprehensively oriented. In terms of the respiratory system, the following data were obtained: the respiratory rate was 26 per minute; during auscultation, the breathing was harsh; moist medium-bubble rales were heard on forced exhalation, more in the middle third on the left. Saturation was 88% in atmospheric air. In terms of the cardiovascular system, the data were the following: hypotension and tachycardia (blood pressure 70/40 mm Hg, heart rate 104 beats/min). During the examination of the gastrointestinal tract, a white coating was noted over the entire surface of the tongue. No significant changes were found in terms of the other organs and systems. Pneumocystis pneumonia and cytomegalovirus infection with lung damage were suspected.

Laboratory studies covered a wide range of indicators. Hemogram was normal. C-reactive protein was 127.40 mg/l, ferritin was 334.57 ng/ml, and procalcitonin was >10.00 ng/ml. The biochemical blood test revealed hypoproteinemia, hypoalbuminemia, bilirubinemia, and signs of renal failure (total protein 46.3 g/l, albumin 27.1 g/l, total bilirubin 44.9 μmol/l, direct bilirubin 32.8 μmol/l, urea 10.3 mmol/l, and creatinine 190.6 μmol/l). The indicator of cHCO3 was 19.1 mmol/l, BBA was -7.6 mmol/l, BE was ‑7.1 mmol/l, pH was 7.286; coagulogram data were without pathological changes; D-dimer was 597 ng/ml; CD4 lymphocytes amounted to 54 cells/μl; HIV viral load (VL) was 369,224 copies/ml; mycobacteria were not detected in the blood and sputum. Blood and sputum were taken for microbiological and molecular biological testing on the presence of genetic material of pathogens of the secondary infections. In addition, instrumental studies were carried out to establish a diagnosis. Chest X-ray revealed bilateral polysegmental pneumonia with predominant damage to the right lung. Echocardiography showed that the contractility of the LV myocardium was satisfactory; sclerotic changes in the aortic and mitral valves, as well as grade 1 mitral insufficiency, were found. Ultrasound of the abdominal organs, kidneys, retroperitoneal space, lymph nodes, and pleural cavity revealed the enlargement and diffuse changes in the liver parenchyma, diffuse changes in the pancreatic parenchyma, moderate enlargement and diffuse changes in the spleen parenchyma, diffuse changes in the parenchyma of both kidneys, and a small amount of free fluid in the right and left pleural cavities.

In the department, the patient received respiratory support in the form of high-flow oxygen therapy (HFO) at a rate of 5‒7 l/min, which made it possible to increase the saturation to 95–97%. Upon admission, the patient received intravenous ciprofloxacin, intravenous ceftriaxone, intravenous co-trimoxazole, and intravenous fluconazole as etiotropic therapy. From the 2nd day of hospitalization, antibacterial therapy was optimized by prescribing intravenous ertapenem and intravenous vancomycin. The patient also received pathogenetic and symptomatic therapy in the form of infusions of ionic solutions, mucolytics, glucocorticosteroids, and nonsteroidal anti-inflammatory drugs.

Despite the therapy, shortness of breath and pulmonary heart failure persisted; at maximum parameters of the HFO therapy, the patient was periodically under desaturation. At the end of the second day of the hospital period, cardiopulmonary arrest was recorded, resuscitation measures were ineffective, biological death was confirmed. The posthumous diagnosis was “B20.7 HIV infection, stage 4B, progression phase on ART: bilateral pneumonia of unspecified etiology, oropharyngeal candidiasis.” Complications of the underlying disease included grade 2‒3 respiratory failure, bilateral pleurisy, cerebral edema, and pulmonary heart failure. Concomitant diseases included chronic viral hepatitis C. The body was sent to the pathological anatomy department.

The laboratory tests of the autopsy material from the lungs included both microbiological and molecular biological investigations for the presence of DNA of pathogens of opportunistic infections: DNA of Candida albicans, Candida glabrata, Candida krusei, Pneumocystis jirovecii, Mycoplasma pneumoniae, Chlamydia pneumoniae, Cytomegalovirus, Cryptococcus neoformans, Staphylococcus spp., Staphylococcus aureus, Mycobacterium tuberculosis complex, as well as SARS-CoV-2 (negative result).

Based on the results of the autopsy examination, the pathoanatomical diagnosis was: “Underlying disease: HIV infection, stage 4B, progression phase on ART. Secondary diseases: Bilateral pneumonia with total damage to both lungs and abscess formation (culture of a lung fragment revealed growth of Klebsiella pneumoniae); qualitative PCR revealed Epstein-Barr virus DNA in a smear from the surface of a lung section. Complications: Diffuse alveolar damage, acute phase, DIC syndrome, bilateral exudative pleurisy, pulmonary edema, acute renal failure, cerebral edema. Concomitant diseases: Chronic viral hepatitis C. Chondromatous hamartoma S1 of the right lung. Apical fibrosis of the right lung.” Thus, the cause of death of the HIV-infected patient was bilateral pneumonia caused by Klebsiella pneumoniae, which progressed aggressively with the development of pleurisy, diffuse alveolar damage, systemic inflammatory response syndrome, and acute respiratory failure at the end of the disease. Besides, it is impossible to reliably assert an etiological link between the Epstein-Barr virus (EBV) and pneumonia, since this requires quantitative PCR analysis, and qualitative detection of EBV DNA is not proof of this link [6].

Conclusion

From a formal point of view, the patient was hospitalized twice during the year with the diagnosis of pneumonia. In this case, the necessary criteria are present to justify the clinical stage 4B of HIV infection. On the other hand, there was only one day between the two hospitalizations, which actually indicates the presence of a single episode of CAP. With such an interpretation of the course of the disease, we can only talk about stage 4A of HIV infection caused by oropharyngeal candidiasis and combined CAP. However, in this patient, the course of pneumonia was aggressive, caused by opportunistic flora and accompanied by severe immunodeficiency that does not allow pneumonia to be considered separately from HIV infection.

Thus, practicing physicians providing care to HIV-infected patients should take into account the high prevalence of CAP and its possible complicated course and conduct a thorough collection of anamnesis for the previous year before the current hospitalization. In addition, they should use molecular biological methods for quantitative assessment of herpesvirus DNA, have regard to the probability of opportunistic resistant flora when choosing antibacterial therapy, and also take into consideration the advisability of using the “Recommendations for the treatment of HIV infection and associated diseases, chemoprophylaxis of HIV infection” revised in 2023, as they are supplemented with a section on the management of HIV-infected patients with bacterial pneumonia.