Advanced HIV disease: A review of diagnostic and prophylactic strategies.

BACKGROUND: Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization's (WHO) 'test-and-treat' strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first-line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point-of-care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD. METHODS: We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions. RESULTS: While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non-sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource-poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care. CONCLUSIONS: Despite progress with HIV treatment and prevention, a persistent 20%-30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV-related morbidity and mortality. Investment in the development of additional POC or near-bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same-day results. However, in real-world scenarios, people with AHD have multiple comorbidities and imperfect follow-up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

Minimally Invasive Adenocarcinoma of the Lung as Second Malignant Neoplasm Following Pediatric Rhabdomyosarcoma.

Primary pulmonary tumors are extremely rare in the pediatric population; however, sporadic cases of invasive pulmonary adenocarcinoma as a second malignant neoplasm (SMN) have been described in survivors of pediatric cancers. Pediatric patients with rhabdomyosarcoma (RMS) have a particularly increased risk of developing a SMN when compared to the general population, though pulmonary adenocarcinoma has not been previously described in a RMS patient. A 12-year-old female previously treated for stage IV pelvic RMS was found to have a left pulmonary nodule on surveillance computed tomography. The nodule was detected 4.25 years after the completion of treatment, which included resection, chemotherapy, and radiation to the abdomen and pelvis. Wedge resection of the pulmonary lesion was performed with negative margins. Histopathological examination revealed minimally invasive adenocarcinoma. Pulmonary adenocarcinoma may rarely present as a SMN in pediatric cancer survivors. The pathogenesis of this association is not yet entirely clear, but may include chemotherapy-induced mutagenesis and/or genetic predisposition. As pulmonary adenocarcinoma may present as a lung lesion radiographically indistinguishable from metastatic RMS, it should be considered in the differential diagnosis of any pediatric RMS survivor presenting with a new pulmonary nodule, especially in cases with late recurrence.

The diagnostic performance of the Visitect Advanced Disease point-of-care CD4 platform: a pragmatic mixed-methods multisite validation, costing, and qualitative analysis.

BACKGROUND: The Visitect CD4 Advanced Disease test (AccuBio, Alva, United Kingdom) is a rapid, semi-quantitative assay that estimates CD4 results above or below 200 cells/µL. We evaluated the performance of the Visitect CD4 assay in semi-urban laboratories in Uganda. METHODS: We performed a pragmatic laboratory validation of the Visitect CD4 platform in four routine HIV clinics in Uganda, nested within a cluster randomized trial evaluating an enhanced package of screening and treatment for persons with advanced HIV disease (NCT05085171). As part of the clinical trial, samples processed on the Visitect CD4 platform were confirmed using another CD4 testing method. We compared the diagnostic performance of the Visitect CD4 platform against the confirmatory method by evaluating the sensitivity, specificity, positive and negative predictive values. RESULTS: Of 1495 venous blood samples that were processed both by the Visitect CD4 test and another confirmatory CD4 platform at clinics in Kampala, Uganda, specificity was 81% (95% CI, 79%-84%) and the positive predictive value was 69% (95% CI, 66%-73%). There were no samples for which the Visitect test was >200 cells/µL and the confirmatory test was ≤200 cells/µL, resulting in a sensitivity of 100%. Among Visitect CD4 tests that were read as <200 cells/µL with confirmatory results >200 cells/µL, the median confirmatory CD4 result was 397 (IQR, 281-590) cells/µL. Specificity varied by clinic ranging from 63% to 99%. CONCLUSIONS: Given variable specificity of the Visitect CD4 Advanced Disease platform, successful implementation will require consideration of clinic context and laboratory staffing.

Hyponatremia as a Predictor of Cryptococcal Meningitis and Death Among Asymptomatic Persons With HIV and Cryptococcal Antigenemia.

Among persons with human immunodeficiency virus-associated cryptococcal meningitis serum hyponatremia is a risk factor for mortality; however, the role of hyponatremia in persons with asymptomatic cryptococcal antigenemia is unknown. We found that serum hyponatremia ≤130 mmol/L is an independent risk factor for progression to meningitis and death in asymptomatic persons with cryptococcal antigenemia.

Pediatric Infectious Diseases Milestones: A Step in the Right Direction to Evaluate Subspecialty Learners.

We share the work of the ACGME Pediatric Infectious Diseases Working Group in creating the Pediatric Infectious Diseases-Specific Milestones and discuss key considerations that lead to the reformation of competencies to better assess learners in Pediatric Infectious Diseases.