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There are emerging reports of false-positive HIV nucleic acid testing (NAT) in patients who have received chimeric antigen receptor (CAR) T-cell therapies. We present a case of a 66-year-old-woman with primary-refractory stage IIIA double-hit high-grade B-cell lymphoma, in whom we detected false-positive HIV-1 NAT results after receipt of a third-generation self-inactivating investigational lentivirus-based CAR T-cell therapy. We reviewed the current state of the science on HIV-1 NAT and found that all reported false-positive cases have occurred in the setting of lentivirus-based CAR T-cell therapy and testing with FDA-approved platforms targeting the 5'LTR genomic region. Herein, we offer recommendations for HIV diagnostic testing in patients undergoing this mode of therapy. Clinicians managing this patient population should be aware of cross-reactivity between these therapeutic agents and commonly used HIV-1 NAT assays. [ABSTRACT FROM AUTHOR]

Inflammation in early human immunodeficiency virus type 1 (HIV-1) disease progression is not well characterized. Ninety patients with untreated primary HIV-1 infection were studied to determine associations of inflammatory proteins with early disease progression. High plasma tumor necrosis factor α (TNF-α) levels (≥8.5 pg/mL) were significantly associated with an increased viral load set point and shorter times to reaching a CD4(+) T-cell count of <500 cells/mm(3) and initiating antiretroviral therapy. The increased risk of reaching a CD4(+) T-cell count of <500 cells/mm(3) in the group with high TNF-α levels was driven by viral load but was independent of concurrent CD4(+) T-cell count. Thus, TNF-α appears to be an important mediator of inflammation in patients with poor viral control and early HIV-1 disease progression. [ABSTRACT FROM AUTHOR]

Dendritic cells have critical roles for generating and finetuning adaptive immune responses and for regulating immune activity through cytokine secretion. In this study, we analyzed functional properties of dendritic cells in primary human immunodeficiency virus type 1 (HIV-1) infection. We found substantial disarray of the functional properties of myeloid and plasmacytoid dendritic cells in acute HIV-1 infection, which included defective antigen-presenting and cytokine secretion properties and was associated with a distinct surface expression profile of immunomodulatory dendritic cell receptors from the leukocyte immunoglobulin- like receptor family. These data indicate that key functional properties of dendritic cells are compromised during primary HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background. Pro-inflammatory monocytes/macrophages may contribute to increased atherosclerosis in human immunodeficiency virus (HIV)-infected patients. We investigatedto our knowledge, for the first timedsCD163 and other markers of monocyte activation in relationship to atherosclerotic plaque in HIV-infected patients. Methods. One hundred two HIV-infected and 41 HIV-seronegative men with equivalent cardiovascular risk factors and without history of coronary artery disease were prospectively recruited and underwent computed tomography coronary angiography. Results. sCD163 levels and presence of plaque were significantly higher among antiretroviral-treated subjects with undetectable HIV RNA levels, compared with seronegative controls (1172±646 vs. 883±561 ng/mL [P=.02] for sCD163 and 61% vs. 39% [P =.03] for presence of plaque). After adjusting for age, race, lipids, blood pressure, glucose, smoking, sCD14, and HIV infection, sCD163 remained independently associated with noncalcified plaque (P =.008). Among HIV-infected patients, sCD163 was associated with coronary segments with noncalcified plaque (r = 0.21; P = .04), but not with calcium score. In contrast, markers of generalized inflammation, including C-reactive protein level, and D-dimer were not associated with sCD163 or plaque among HIV-infected patients. Conclusions. sCD163, a monocyte/macrophage activation marker, is increased in association with noncalcified Conclusions. sCD163, a monocyte/macrophage activation marker, is increased in association with noncalcified coronary plaque in men with chronic HIV infection and low or undetectable viremia. These data suggest a potentially important role of chronic monocyte/macrophage activation in the development of noncalcified vulnerable plaque. [ABSTRACT FROM AUTHOR]

CD163, a monocyte- and macrophage-specific scavenger receptor, is shed during activation as soluble CD163 (sCD163). We have previously demonstrated that monocyte expansion from bone marrow with simian immunodeficiency virus (SIV) infection correlated with plasma sCD163, the rate of AIDS progression, and the severity of macrophage-mediated pathogenesis. Here, we examined sCD163 in human immunodeficiency virus (HIV) infection. sCD163 was elevated in the plasma of individuals with chronic HIV infection (>1 year in duration), compared with HIV-seronegative individuals. With effective antiretroviral therapy (ART), sCD163 levels decreased in parallel with HIV RNA levels but did not return to HIV-seronegative levels, suggesting the presence of residual monocyte/macrophage activation even with plasma viral loads below the limit of detection. In individuals with early HIV infection (≤1 year in duration), effective ART resulted in decreased sCD163 levels that were comparable to levels in HIV-seronegative individuals. sCD163 levels in plasma were positively correlated with the percentage of CD14+CD16+ monocytes and activated CD8+HLA-DR+CD38+ T lymphocytes and were inversely correlated with CD163 expression on CD14+CD16+ monocytes. With ART interruption in subjects with early HIV infection, sCD163 and plasma virus levels spiked but rapidly returned to baseline with reinitiation of ART. This study points to the utility of monocyte- and macrophage-derived sCD163 as a marker of HIV activity that links viral replication with monocyte and macrophage activation. These observations underscore the significance of monocyte and macrophage immune responses with HIV pathogenesis. [ABSTRACT FROM PUBLISHER]

Dendritic cells have critical roles for generating and fine-tuning adaptive immune responses and for regulating immune activity through cytokine secretion. In this study, we analyzed functional properties of dendritic cells in primary human immunodeficiency virus type 1 (HIV-1) infection. We found substantial disarray of the functional properties of myeloid and plasmacytoid dendritic cells in acute HIV-1 infection, which included defective antigen-presenting and cytokine secretion properties and was associated with a distinct surface expression profile of immunomodulatory dendritic cell receptors from the leukocyte immunoglobulin-like receptor family. These data indicate that key functional properties of dendritic cells are compromised during primary HIV-1 infection.