Role of HRCT in Evaluation of Lung Parenchymal Changes in Symptomatic HIV-Seropositive Individuals - Original Research Article

Background: The association between spectrum of pulmonary infection and human immunodeficiency virus (HIV) presents an immediate and grave public health and socio-economic threat, particularly in the developing world. Purpose: The purpose of this study is to demonstrate the different patterns of pulmonary abnormalities in HIV patients, to define imaging features of each disease whether infective, non-infective or HIV associated pulmonary malignancy, to differentiate different pulmonary diseases in HIV patients on the basis of pattern of involvement and localization of lesions. Materials and Methods: The cases were selected based on all patients referred to the Department of Radiology, LLRM Medical College, Meerut with proven HIV/acquired immunodeficiency syndrome (AIDS) infection which was clinically suspected of pulmonary infections. HRCT was done. Results: Total 60 cases of HIV/AIDS with suspected pulmonary disease were studied. Out of which 39 were male and 21 were female. Out of which 51.67 % of patients were diagnosed as having pulmonary TB, followed by bacterial infection in 10 % cases and fungal infection like aspergillus in 5%, pneumocystis jiroveci pneumonia in 2% & cryptococcus in 1% patients, ILD in 3% and thromboembolism in 1% patients while 23.3% of our study did not reveal any significant abnormality. Conclusion: Various findings such as pulmonary TB being the most common infection and most common HRCT finding in pulmonary TB were nodular opacity can be obtained from the present study. HRCT is a highly sensitive tool for detecting parenchymal abnormalities and allows better characterization of the lesions, with better reproducibility and less interobserver difference. Keywords: interstitial lung disease, Enzyme-linked immunosorbent assay, Miliary tuberculosis, Pulmonary tuberculosis, pneumocystis jiroveci pneumonia.

Epidemiology, mortality and effectiveness of prophylaxis for Pneumocystis jiroveci pneumonia among rheumatic patients: a territory-wide study

Background Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection affecting immunocompromised individuals. However, evidence regarding the burden and effectiveness of prophylaxis among rheumatic patients remains limited. Delineating the epidemiology and efficacy of prophylaxis among rheumatic patients is urgently needed. Methods We performed a territory-wide cohort study of rheumatic patients in Hong Kong. All patients with a diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), immune-mediated myositis (IMM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or spondyloarthritis (SpA) between 2015 and 2019 were included. Prevalence, frequency of prophylaxis and mortality of PJP were calculated. Number needed to treat (NNT) analysis was also performed. Results Out of 21,587 patients (54% RA, 25% SLE, 13% SpA, 5% IMM, 2% AAV and 1% SSc), 1141 (5.3%) patients were prescribed PJP prophylaxis. 48/21,587 (0.2%) developed PJP. No patients who developed PJP received prophylaxis prior to infection. The incidence of PJP was highest among SSc, AAV, and IMM patients. Among these diseases, the majority of PJP occurred while patients were on glucocorticoids at daily prednisolone-equivalent doses of 15 mg/day (P15) or above. PJP prophylaxis was effective with NNT for SSc, AAV and IIM being 36, 48 and 114 respectively. There were 19 PJP-related mortalities and the mortality rate was 39.6%. Conclusion PJP is an uncommon but important infection among rheumatic patients, PJP prophylaxis is effective and should be considered in patients with SSc, AAV and IMM, especially those receiving glucocorticoid doses above P15.

Combining Atovaquone with Intensive Conventional Chemotherapy for Pediatric Acute Myeloid Leukemia (AML) Is Feasible and Well Tolerated

Background Relapse free survival of pediatric AML remains only 60%. Current standard myelosuppressive therapy has been maximized, so novel therapies with minimal toxicities are needed to improve outcomes. Previously, we found atovaquone (AQ), an FDA-approved drug that treats pneumocystis jiroveci pneumonia (PJP), reduces AML burden - by suppressing oxidative phosphorylation (OXPHOS) - in xenograft mice. Clinically achievable concentrations of AQ for anti-PJP are 40-80µM, but the anti-leukemia effects are observed as low as 10µM (Stevens et al, Bld Adv, 2019). This makes AQ an ideal drug to incorporate into AML treatment. AQ is a daily administered oral medication, and plasma levels depend on patient compliance, absorption, and entero-hepatic recirculation, which can be compromised due to the patient population and adverse events (AE) of chemotherapy. Here we investigated the feasibility of incorporating AQ into standard pediatric AML treatment. Methods Patients with de novo AML were enrolled at two children's hospitals in the USA. Daily administration of AQ at established PJP prophylaxis dosing was combined with standard chemotherapy for AML, based on the Medical Research Council (MRC) backbone of cytarabine 100mg/m2 q12h x 10 days, and daunorubicin 50mg/m2/dose on days 1, 3, and 5. As it was unclear if our AQ dosing would provide adequate PJP prophylaxis, it was left to provider discretion to give additional PJP protection. AQ compliance, AEs (per NCI CTCAE v5), parent/caregiver ease of administration score (scale: 1-5, 1=very difficult, 5=very easy to administer) and peripheral blood/bone marrow pharmacokinetics (PK) were collected during Induction 1. Real time AQ plasma concentration results were not provided. To address feasibility of achieving adequate levels, all gastrointestinal (GI) AEs ≥ grade 2 were collected, in addition to grade 4 or greater AEs. Patients who took at least 85% of planned doses and missed less than 2 consecutive doses of AQ were eligible for analyses. Correlative biology studies assessed AQ induced apoptosis at 30uM, effects on OXPHOS and relevant signaling activities. Patient derived xenografts (PDX) were established and treated with AQ. This trial is registered with ClinicalTrials.gov (NCT03568994). Results A total of 26 pediatric AML patients enrolled (ages 8 months - 19.7 years, mean 10.7 years); 24 patients were evaluable for this study. Two patients had Grade ≥ 3 GI toxicities that prohibited enteral administration so they were excluded from AQ PK and ease of administration analyses. We found that 14/24 (58%) patients achieved plasma levels above the target anti-leukemia concentration (10µM) by day 11. At the end of induction, 19/24 (75%) patients achieved plasma levels above 10µM, but only 7/24 (29%) patients achieved adequate levels for PJP prophylaxis (40µM). Only 1 patient achieved levels above 40µM throughout the trial [FIG A]. Mean ease of administration score was 3.8. For the youngest patients (x ≤ 2.6years), the average score was 3.4 which was not significantly different from older patients (ANOVA, p > 0.05) [FIG B]. Ease of administration scores showed no association with plasma levels (Pearson's correlation, p > 0.05). Finally, correlative biology studies in patient samples demonstrated robust AQ-induced apoptosis, OXPHOS suppression, and prolonged survival in a PDX model receiving AQ [FIG C]. Conclusion Our data demonstrate the feasibility of combining AQ with traditional chemotherapy for pediatric AML. Patients of all ages were able to tolerate AQ and no AEs were attributable to AQ administration. The target anti-leukemic concentration of AQ in the plasma (> 10uM) was frequently achieved, but concentrations of > 40uM at standard dosing were rare. Low plasma levels of AQ did not correlate with the presence of GI related AEs or weight loss, so plasma levels should be monitored to ensure sufficient PJP prophylaxis. Our correlative biology results support suppression of OXPHOS as the primary mechanism of action by which AQ exerts its anti-leukemia effect, and AQ may be an active anti-leukemia agent for pediatric AML patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

336. COVID-19 and Pneumocystis jiroveci Pneumonia

Background More accounts of opportunistic infection in COVID-19 patients are emerging. At our institution, we identified 2 COVID-19 patients with Pneumocystis jiroveci pneumonia (PJP) opportunistic infection. This prompted a review of the literature to identify trends in patient characteristics, risk factors, and outcomes in this population. Methods A literature review was conducted using PubMed that identified 13 other patients with both COVID-19 and PJP infection. Age, gender, human immunodeficiency virus (HIV) status, other immunocompromised states, time between COVID-19 and PJP diagnosis, and clinical outcomes were captured for analysis. Results Eleven patients were male. The average age was 56 years. All but 2 patients were immunocompromised. At time of PJP diagnosis, seven patients had newly diagnosed HIV and one had known, well-controlled HIV. One patient had rheumatoid arthritis receiving leflunomide, 1 had ulcerative colitis receiving budesonide and sulfasalazine, 2 patients had multiple myeloma whereby both were on lenalidomide, 1 patient was a renal transplant recipient immunosuppressed on tacrolimus, mycophenolate, and methylprednisolone, and 1 patient had chronic lymphocytic leukemia getting fludarabine, cyclophosphamide, and rituximab. Nine patients had positive COVID-19 and PJP tests performed within 7 days of one another. One patient tested positive for PJP 54 days into admission for COVID-19. This patient received high dose steroids and tocilizumab for initial COVID-19 infection. Three patients were re-hospitalized with PJP after a recent admission for COVID-19 pneumonia, with a mean time to readmission of 25 days. One of these 3 patients had no treatment for COVID-19, while 2 received steroids. Five of the total 15 patients (33%) died. Conclusion COVID-19 treatments with high dose steroids and tocilizumab can make patients vulnerable for opportunistic infection with PJP. Furthermore, COVID-19 is known to cause lymphopenia which may further increase this risk. A diagnosis of concomitant PJP can be especially challenging due to nearly identical radiographical findings. Serum beta-D glucan and HIV testing can be especially helpful in this situation, and there should be a low threshold for performing bronchoalveolar lavage. Disclosures All Authors: No reported disclosures

The Evaluation of the Factors Affecting Mortality in Cases of HIV-infected Pneumocystis Jiroveci Pneumonia

Objective: Pneumocystis jiroveci pneumonia (PJP) is a common opportunistic infection in human immunodeficiency virus (HIV) infection cases. This study aimed to investigate the mortality rate and the factors affecting mortality in HIV-infected PJP cases followed in our clinic. Methods: In this study HIV (+) cases followed up in our clinic between 2012-2019 were included. Age, sex, comorbidity status, LDH, CD4, lymphocyte, albumin, values, and blood gas results of these patients were recorded at the time of diagnosis. Results: Twenty-eight patients with the diagnosis of HIV-infected PJP were included in the study. The mean age of the patients was 45.7 years, and the male ratio was 78.6% (18/28). The overall hospital mortality rate was 35.7% (10/28) among the cases. Conclusions: As a result, performing studies involving many patients may be beneficial in these patients for diagnosis, follow-up and early treatment.