There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.21178

Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22759

Diagnosis, management, and treatment of hepatitis C: An update

Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection.

PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression

The mechanisms underlying CD4+ T cell depletion in human immunodeficiency virus (HIV) infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. Here, we studied the effect of HIV infection on the activation and depletion of defined subsets of CD4+ and CD8+ T cells in the blood, gastrointestinal (GI) tract, and lymph node (LN). We also measured HIV-specific T cell frequencies in LNs and blood, and LN collagen deposition to define architectural changes associated with chronic inflammation. The major findings to emerge are the following: the GI tract has the most substantial CD4+ T cell depletion at all stages of HIV disease; this depletion occurs preferentially within CCR5+ CD4+ T cells; HIV-associated immune activation results in abnormal accumulation of effector-type T cells within LNs; HIV-specific T cells in LNs do not account for all effector T cells; and T cell activation in LNs is associated with abnormal collagen deposition. Taken together, these findings define the nature and extent of CD4+ T cell depletion in lymphoid tissue and point to mechanisms of profound depletion of specific T cell subsets related to elimination of CCR5+ CD4+ T cell targets and disruption of T cell homeostasis that accompanies chronic immune activation.

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CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract

Head and Neck Infections Pulmonary Infections Endovascular Infections Gastrointestinal and Abdominal Infections Sexually Transmitted Diseases AIDS Skin and Soft Tissue Infections of the Eye and Orbit Infections of the Central Nervous System Mycobacterial Disease Viral Diseases

Atlas of infectious diseases.

Mycobacterium bovis infection of an implantable defibrillator following intravesical therapy with bacille Calmette-Guérin.

Objective
To determine the etiology and clinical predictors of peripheral lymphadenopathy in HIV-infected individuals during the antiretroviral (ARV) era in a non-Tuberculosis endemic setting.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1468-1293.2012.01035.x

Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults.

We assessed the incidence of antiretroviral drug resistance in a cohort of 25 antiretroviral-naive, human immunodeficiency virus-positive inmates in Massachusetts. Silent mutations, unexpected mutations at resistant sites, and resistance mutations were recorded. Among these inmates, we found a prevalence of drug resistance mutations that was equivalent to the prevalence previously found in nonprison populations in the same state.

Antiretroviral Drug Resistance Mutations in Antiretroviral-Naive Prisoners

China is a region of the world with a rapidly spreading HIV-1 epidemic. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to support the design and testing of an effective HIV-1 vaccine for this population. HIV-1-specific T cell responses were characterized in 32 HIV-1-infected individuals of Chinese origin and compared to 34 infected caucasians using 410 overlapping peptides spanning the entire HIV-1 clade B consensus sequence in an IFN-γ ELISpot assay. All HIV-1 proteins were targeted with similar frequency in both populations and all study subjects recognized at least one overlapping peptide. HIV-1-specific T cell responses clustered in seven different regions of the HIV-1 genome in the Chinese cohort and in nine different regions in the caucasian cohort. The dominant HLA class I alleles expressed in the two populations differed significantly, and differences in epitope clustering pattern were shown to be influenced by differences in class I alleles that restric...

Differences in the Expressed HLA Class I Alleles Effect the Differential Clustering of HIV Type 1-Specific T Cell Responses in Infected Chinese and Caucasians

David Stone

Papers

Atlas of infectious diseases.

Mycobacterium bovis infection of an implantable defibrillator following intravesical therapy with bacille Calmette-Guérin.

Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults.

Antiretroviral Drug Resistance Mutations in Antiretroviral-Naive Prisoners

Differences in the Expressed HLA Class I Alleles Effect the Differential Clustering of HIV Type 1-Specific T Cell Responses in Infected Chinese and Caucasians