SUMMARY
Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.
Invasive aspergillosis (IA) is in an important opportunistic infection affecting transplant patients. 1,2 While all solid organ transplant recipients are at risk for invasive aspergillosis, liver transplant patients appear to be at particularly high risk for disseminated disease and have poor outcomes, with mortality ranging from 64% to 100%. 1,3 For liver transplant recipients, time to onset of IA after transplant is decreased when compared to other organ transplant recipients. 1,3,4 Additionally, liver disease itself, in the absence of a transplant, portends an increased risk for IA. [1][2][3]5,6 Typically, IA is caused by Aspergillus fumigatus and the most frequent manifestation of infection is invasive pulmonary disease. 1 However, disseminated aspergillosis including, intraabdominal, intravascular and neurological involvement is not uncommon. [1][2][3][4]6 While pulmonary IA can be relatively simple to diagnose with use of respiratory samples, serum antigens and imaging, central nervous system (CNS) IA can pose diagnostic challenges which are associated with delayed diagnosis and poor outcomes. 1,3,[5][6][7] Microbial cell-free DNA sequencing (mcfDNA) is a diagnostic modality that has recently shown value as an adjunctive test for the diagnosis of fungal pneumonia in stem-cell transplant patients. 8 When compared to standard diagnostic methods, use of mcfDNA had a 51% sensitivity and 100% specificity. Herein, we present a case demonstrating the utility of this novel diagnostic technique in the diagnosis of fungal brain abscesses in a patient who had recently undergone liver transplantation.
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