Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.

Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV-Infected Immunocompromised Patients with Pneumocystis jirovecii Pneumonia.

The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence in HIV-infected patients after the introduction of antiretroviral therapy (ART) in resource-rich settings and the growing number of non-HIV-infected immunocompromised patients at risk leads to considerable epidemiologic changes with clinical, diagnostic, and treatment consequences for physicians. HIV-infected patients usually develop a subacute course of disease, while non-HIV-infected immunocompromised patients are characterized by a rapid disease progression with higher risk of respiratory failure and higher mortality. The main symptoms usually include exertional dyspnea, dry cough, and subfebrile temperature or fever. Lactate dehydrogenase may be elevated. Typical findings on computed tomography scans of the chest are bilateral ground-glass opacities with or without cystic lesions, which are usually associated with the presence of AIDS. Empiric treatment should be initiated as soon as PCP is suspected. Bronchoalveolar lavage has a higher diagnostic yield compared to induced sputum. Immunofluorescence is superior to conventional staining. A combination of different diagnostic tests such as microscopy, polymerase chain reaction, and (1,3)-ß-D-glucan is recommended. Trimeth-oprim/sulfamethoxazole for 21 days is the treatment of choice in adults and children. Alternative treatment regimens include dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or pentamidine. Patients with moderate to severe disease should receive adjunctive corticosteroids. In newly diagnosed HIV-infected patients with PCP, ART should be initiated as soon as possible. In non-HIV-infected immunocompromised patients, improvement of the immune status should be discussed (e.g., temporary reduction of immunosuppressive agents). PCP prophylaxis is effective and depends on the immune status of the patient and the underlying immunocompromising disease.

Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. RESEARCH QUESTION: What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? STUDY DESIGN AND METHODS: In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP < 12.5 mg/kg/d) and conventional-dose (TMP 12.5-20 mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. RESULTS: Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71 mg/kg/d in the low-dose group and 17.78 mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7% vs 18.4%, respectively; P = .080) or 180-day mortality (14.6% vs 26.1%, respectively; P = .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8% vs 59.0%, respectively; P = .005). The initial treatment completion rates were 43.3% and 29.6% in the low-dose and conventional-dose groups (P = .158), respectively. INTERPRETATION: Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.

Pneumocystis pneumonia diagnosed by repeated measurements of ß-D-glucan levels.

ß-D-glucan is extensively employed as a supplementary diagnostic tool for Pneumocystis pneumonia (PCP) and typically yields positive results in most cases. We present a case of a 73-year-old woman with a history of rheumatoid arthritis, who was receiving biological agents and was admitted due to pneumonia. Initially, the ß-D-glucan test was negative. However, as the disease progressed, it eventually turned positive, leading to the diagnosis of PCP. The patient was treated with corticosteroids and trimethoprim-sulfamethoxazole, resulting in pneumonia resolution. Our findings suggest that repeated assessment of ß-D-glucan levels holds diagnostic value in patients without human immunodeficiency virus infection.

Clinical profile and outcome of non-HIV-infected patients with cryptococcal meningitis and malignancy.

BACKGROUND: Cryptococcal meningitis (CM) can coexist with malignancy in patients not infected by human immunodeficiency virus (HIV). The purpose of this study was to evaluate the clinical characteristics and therapeutic outcomes of non-HIV-infected patients with CM with malignancy. METHODS: The study cohort comprised 320 patients diagnosed with CM from January 2013 to May 2019. Malignancy was diagnosed based on the medical history, imaging findings, and pathological findings. One-hundred-and-four patients also underwent positron emission computed tomography (PET-CT) examination to enable the early detection of possible malignancies. The demographics, clinical characteristics, and outcomes were analyzed. RESULTS: Twelve patients with CM with malignancies were found. Seven were patients with CM who had a history of malignancies (CM in malignancy; CIM), while five patients had malignancies detected after being diagnosed with CM (malignancy in CM; MIC). The patients with CM with malignancies, especially MIC, were older than those without malignancies. The outcome was similar for patients with CIM and patients with CM without malignancy, but was extremely poor for patients with MIC. PET-CT examination suggested malignancy in five of 104 patients, with malignancy finally confirmed in four of five patients. CONCLUSIONS: Compared with the general population, the rate of solid malignancies was increased in patients with CM, especially older adults. The presence of malignancies and timing of discovery were closely related to the outcome of patients with CM. Thus, it is necessary to screen for malignancies in older adults with CM. PET-CT might be useful for early malignancy screening of patients with CM.

Diagnostic accuracy of (1→3)-ß-D-glucan to predict Pneumocystis jirovecii pneumonia in non-HIV-infected patients.

Background Pneumocystis jirovecii pneumonia (PCP) is a common and potentially fatal opportunistic infection in immunocompromised non-HIV individuals. There are problems with clinical and diagnostic protocols for PCP that lack sensitivity and specificity. We designed a retrospective study to compared several methods that were used in diagnostics of PCP. Patients and methods One hundred and eight immunocompromised individuals with typical clinical picture for PCP and suspicious radiological findings were included in the study. Serum samples were taken to measure the values of (1→3)-ß-D-glucan (Fungitell, Associates of Cape Cod, USA). Lower respiratory tract samples were obtained to perform direct immunofluorescence (DIF, MERIFLUOR® Pneumocystis, Meridian, USA) stain and real-time PCR (qPCR). Results Fifty-four (50%) of the 108 patients in our study had (1→3)-ß-D-glucan > 500 pg/ml. Patients that had (1→3)-ß-D-glucan concentrations < 400 pg/ml in serum, had mean threshold cycles (Ct) 35.43 ± 3.32 versus those that had (1→3)-ß-D-glucan concentrations >400 pg/mL and mean Ct of 28.97 ± 5.27 (P < 0.001). If we detected P. jirovecii with DIF and qPCR than PCP was proven. If the concentration of (1→3)-ß-D-glucan was higher than 400 pg/ml and Ct of qPCR was below 28.97 ± 5.27 than we have been able be certain that P. jirovecii caused pneumonia (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.62-3.27, P < 0.001). Conclusions Measurement of (1→3)-ß-D-glucan or qPCR alone could not be used to diagnose PCP. Diagnostic cut-off value for (1→3)-ß-D-glucan > 400pg/ml and qPCR below 30 Ct, allow us to conclude that patient has PCP. If the values of (1→3)-ß-D-glucan are < 400 pg/ml and qPCR is above 35 Ct than colonization with P. jirovecii is more possible than PCP.

Clinical characteristics, treatment outcomes, and prognostic factors of Pneumocystis pneumonia in non-HIV-infected patients.

Objectives: The incidence of Pneumocystis pneumonia (PCP) has been increasing among non-HIV-infected patients. Here, we investigated the clinical characteristics, treatment outcomes, and prognostic factors of PCP in non-HIV-infected patients. Patients and methods: Information on clinical characteristics, treatment outcomes, and prognostic factors of PCP patients who were treated at a medical center in northern Taiwan from October 2015 to October 2016 were retrieved from medical records and evaluated. Results: Among the patients with PCP included in the study, 84 were non-HIV-infected and 25 were HIV-infected. Non-HIV-infected patients with PCP had a longer duration between radiographic findings and treatment (P<0.001), and a higher rate of hospital-associated PCP (P<0.001), hypoxia (P=0.015), respiratory failure (P<0.001), and mortality (P=0.006) than HIV-infected patients with PCP. Among non-HIV-infected patients, non-survivors had a higher fungal burden (46.2% vs 22.2%, P=0.039), higher requirement for adjunctive steroid treatment (94.9% vs 71.1%, P=0.011), and higher rate of pneumothorax (17.9% vs 2.2%, P=0.038) than survivors. Multiple logistic regression revealed that lymphopenia (odds ratio [OR] =3.24, 95% confidence interval [CI] =1.07-9.79; P=0.037), adjunctive steroid use (OR =6.23, 95% CI =1.17-33.14; P=0.032), and pneumothorax (OR =10.68, 95% CI =1.00-113.93; P=0.050) were significantly associated with increased 60-day mortality among non-HIV-infected PCP patients. Conclusion: Lymphopenia, adjunctive steroid therapy, and pneumothorax were significantly associated with higher mortality in non-HIV-infected patients with PCP.