ECMO Support in HIV/AIDS with Pneumocystis Jirovecii Pneumonia: A Case Report and Short Review

We report a case of a patient with novel human immunodeciency virus (HIV) and Pneumocystis jirovecii pneumonia (PJP) was successfully treated with veno-venous (V-V) ECMO owing to refractory hypoxemia and pneumomediastinum, and eventually discharged. In addition to the case report, several previous reports were reviewed for the discussion of some key therapies. was to presented with the shortness of The patient showed a deteriorated oxygenation due to increasing pulmonary inltrates and development of pneumomediastinum, necessitating ECMO. The diagnosis of ARDS, HIV, PJP was made. Trimethoprim/sulfamethoxazole (TMP/SMX) was provided for the treatment of After days of ECMO therapy, was successfully decannulated and eventually and an HIV viral load of 405,000 copies/mL. Simultaneously, three pathogens were found using next-generation sequencing (NGS) in the bronchoalveolar lavage uid (BALF), namely, Pneumocystis jirovecii, Human betaherpesvirus 7, and Acinetobacter baumannii. The patient was treated for PJP with Trimethoprim/sulfamethoxazole (TMP/SMX). In addition, the patient received methylprednisolone at a daily dose of 80mg. ECLS benet adult HIV/AIDS patients with refractory hypoxemia to acute PJP.


Abstract Background
We report a case of a patient with novel human immunode ciency virus (HIV) and Pneumocystis jirovecii pneumonia (PJP) was successfully treated with veno-venous (V-V) ECMO owing to refractory hypoxemia and pneumomediastinum, and eventually discharged. In addition to the case report, several previous reports were reviewed for the discussion of some key therapies.
Case report: A 30-year-old male patient was admitted to the our hospital presented with the shortness of breath. The patient showed a deteriorated oxygenation due to increasing pulmonary in ltrates and development of pneumomediastinum, necessitating ECMO. The diagnosis of ARDS, HIV, PJP was made.
Trimethoprim/sulfamethoxazole (TMP/SMX) was provided for the treatment of PJP. After 7 days of ECMO therapy, the patient was successfully decannulated and eventually discharged.
Conclusions ECMO may bene t adult patients with HIV/AIDS and refractory hypoxemia due to severe PCP. Post-ECMO antiretroviral therapy could improve outcomes.

Background
Acute respiratory failure (ARF), caused by pneumocystis jirovecii pneumonia (PJP), is the major cause of hospitalization in patients with human immunode ciency virus (HIV) [1]. PJP is a serious HIV complication, carrying a mortality rate of 43%, and a critical need for mechanical ventilation (MV) [2].
Extracorporeal life support (ECLS) is a useful salvage therapy approach for treating severe acute respiratory distress syndrome (ARDS) in patients fail to respond to MV [3,4]. Till date, the Extracorporeal Life Support Organization (ELSO) has not offered any absolute contraindications to extracorporeal membrane oxygenation (ECMO). However, ECMO is typically avoided in HIV/AIDS patients, due to poor outcomes and absence of obvious clinical guidelines for HIV-infected or AIDS patients. However, emerging evidences demonstrated the successful usage of ECMO in HIV-positive patients with ARF and PJP infection. The development of highly active antiretroviral therapies (HAART) contribute to the signi cant prolongation of life expectancy of HIVinfected patients [5,6]. Therefore, now, there is a growing interest in ECLS usage for ARF therapy in HIV patients.
Herein, a HIV-infected patient with ARDS, complicated by PJP, was effectively treated with veno-venous (VV) ECMO. Meanwhile, a literature review was performed to discuss the major therapeutic factors, such as MV parameters, ECMO requirements, and duration of highly active antiretroviral therapy (HARRT).

Case Presentation
A male, aged 30 years, with height 170cm and weight 65kg, and no previous history of severe illness, visited the Emergency Department of our hospital in June 2020 for treatment of worsening shortness of breath for one week, fever (> 40°C), and productive cough. Laboratory examination revealed signi cant alterations in hemoglobin (9.6 g/dL), hematocrit (28.8%), and lymphocyte (0.8 g/L) levels. Moreover, diffused ground glass bilateral opacities (DGGBO) were observed on chest X-ray. Hence, the patient was hospitalized at our care center.
During hospitalization, the patient received oxygen supplementation via nasal cannula at 3 L/min, conservative uid management, and empirical antibiotic treatment with piperacillin/tazobactam, yet there was no amelioration of respiratory status. Considering the aggravation of respiratory function, on the 3nd day after hospitalization, the patient was provided with non-invasive positive pressure ventilation (NPPV) to sustain arterial oxygen saturation.
On Day 5 after admission, the patient exhibited further deterioration in respiratory status (respiratory rate of 40 breaths/min; PaO 2 of 50 mmHg on FiO 2 of 0.6). Thus, the patient was moved to the intensive care unit (ICU) and was provided with endotracheal intubation with MV support. Computerized tomography (CT) (Fig. 1) scan of the chest revealed DGGBO with massive basal consolidation and mediastinal emphysema.
Despite optimal sedation, analgesia, and neuro-muscular paralysis, adequate oxygen was not achieved with lung protective ventilation and the patient developed hypoxia refractory to MV. The PaO 2 /FiO 2 was 73.70 mm Hg on 100 % of FiO 2 and 10 cm H 2 O of positive end-expiratory pressure (PEEP).
A therapy decision of using V-V ECMO was made considering the value of PaO 2 /FiO 2 of < 80 mmHg on 100% of FiO 2 and to enable lung protective ventilation, stop progression of mediastinal emphysema and maintain arterial oxygen saturation. A 23 French drainage cannula was placed percutaneously into the inferior vena cava via the femoral approach and another 19 French return cannula was positioned inside the right internal jugular vein. Subsequently, the patient was started on a circuit ow of 4.5 L/min and sweep gas of 4.0 L/min of oxygen (FiO 2 of 100%). Moreover, MV was replaced with ultra-protective strategy using Pressure Control Ventilation (Table 1). The patient was suspected to have HIV infection on admission, owing to a positive HIV antigen-antibody screening test. This was further veri ed with CD4 + T-cell count of 8 cells/L and an HIV viral load of 405,000 copies/mL. Simultaneously, three pathogens were found using next-generation sequencing (NGS) in the bronchoalveolar lavage uid (BALF), namely, Pneumocystis jirovecii, Human betaherpesvirus 7, and Acinetobacter baumannii. The patient was treated for PJP with Trimethoprim/sulfamethoxazole (TMP/SMX). In addition, the patient received methylprednisolone at a daily dose of 80mg.
In time, the chest X-ray and arterial blood gas analysis demonstrated amelioration of the respiratory symptoms and a successful decannulation was performed 7 days after VV ECMO support. The following day, the patient was weaned off of ventilator support. 13 days after decannulation, ART was adopted for the patient after successful therapeutic regimens to prevent immune reconstitution in ammatory syndrome (IRIS). Eventually, the patient was discharged from the hospital 13 days after the withdrawal of ECMO (a total of 25 days after admission).

Discussion
In this study, ECMO was adopted successfully in a patient with ARF and PJP infection, with newly diagnosed AIDS. The course of the patient highlighted some important therapeutic factors.
VV ECMO is a last effort treatment for patients with severe ARDS, who no longer respond to MV [4.7]. Despite no description of absolute contraindications in ELSO guidelines to ECMO, treatment of HIV/AIDS patients with VV ECMO may be controversial, owing to the uncertainties regarding HAART e cacy and high mortality rate. Limited reports exist on ECMO therapy in treating ARF in patients with PJP and HIV/AIDS. However, the reported discharge rate of these patients were comparable to other patients receiving V-V ECMO ( Table 2).  [7].
As for the timing of ECLS initiation in PJP, Goodman [10] reported that apart from higher survival rates, the early usage of ECMO during the course of MV can result in a shorter duration of ECMO support in patients. Similarly, Obata [20] also reported that early ECMO introduction can produce early achievement of lung rest management. Capatos G [21] suggested an approach of early ECLS introduction in ARDS patients with AIDS. He proposed that if patients fail to respond to MV, they should be placed on ECLS within 24 hours, without delay. In this case, the duration between MV and ECMO was minimal and this could have contributed to the enhanced clinical outcome of our patient.
PJP infections often produce air ow constriction, due to cyst formation and pneumotoceles, which, when ruptured, can cause air leak syndrome. In the Table 3, 9 out of 19 patients had developed pneumothorax or pneumomediastinum, which deteriorated the respiratory failure, necessitating ECMO. In contrast, ECMO facilitates a decrease in mean airway pressure and respiratory rate, which reduces barotrauma and accelerates lung rest management, is highly bene cial in patients with PJP. Therefore, early introduction of ECMO is advantageous and should be considered in such patients.
As shown in Table 2, all cases who received post-ECMO ART Survived to hospital discharge, whereas 3/7 of the patients with pre-ECMO ART died. Notably, ART inhibits HIV replication, and may produce immune reconstitution in ammatory syndrome [27], which can worsen PJP, particularly in those requiring ECMO support. In this regard, post-ECMO ART is an effective candidate for ARDS therapy in HIV/AIDS patients with PJP.

Conclusions
Early ECMO introduction and aggressive mobilization on ECLS may bene t adult HIV/AIDS patients with refractory hypoxemia owing to acute PJP. Additional investigations are warranted to explore approaches that improve ECMO therapy in these patients.

Declarations
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