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.

/pdf/cd4-t-cell-depletion-during-all-stages-of-hiv-disease-occurs-113nnyfi1t.pdf

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

Background. Human immunodeficiency virus (HIV)–infected patients with hepatitis C virus (HCV) coinfection are at increased risk for drug-induced liver injury (DILI) compared with patients with HIV infection alone. The mechanism underlying this observation is unknown. We hypothesized that interferon (IFN) would induce biochemical improvement through its anti-inflammatory properties and thereby facilitate the reintroduction of antiretroviral therapy (ART) in patients with DILI. Methods. Patients with symptomatic DILI were referred for evaluation; biopsy of a liver sample was performed for all patients, except 1 with clinical cirrhosis. Results. Twelve patients with acquired immunodeficiency syndrome and symptomatic grade 3/4 hepatotoxicity received treatment with IFN and ribavirin (RBV). Seven of these patients had a history of recurrent DILI. The mean baseline CD4 + T cell counts and HIV RNA levels were 124 cells/mm 3 and 115,369 copies/mL, respectively. Biopsies of liver samples demonstrated significant necroinflammation (mean grade, 10.3) and fibrosis (mean stage, 2.9). Three patients continued to receive ART when they began treatment with IFN-RBV; 9 reinitiated ART within an average of 12 weeks (range, 4–20 weeks) of HCV treatment initiation. All patients attained marked improvement in aminotransferases and continued to receive ART treatment during a mean follow-up regimen of 26.5 months, with subsequent virologic suppression and immunologic reconstitution (mean CD4 + cell count increase, 251/mm 3 ). However, only 1 patient maintained HCV suppression after completion of treatment with IFN-RBV. Conclusions. In patients with symptomatic DILI, treatment with IFN-ribavirin (RBV) led to decreases in aminotransferase levels, which enabled the reinitiation of ART. The beneficial effects of IFN-based therapy may be modulated through the suppression of proinflammatory cytokines, even in virologic nonresponders. Herein, we propose a novel mechanism for DILI, whereby HCV- and HIV-associated inflammatory mediators induce liver injury synergistically.

Managing Symptomatic Drug-Induced Liver Injury in HIV—Hepatitis C Virus—Coinfected Patients: A Role for Interferon

Abstract Background Pre-exposure prophylaxis (PrEP) against HIV infection is available for people at risk of acquiring HIV infection and who are not positive for HIV infection. It is proven to be effective at preventing HIV infection in many studies in various populations. However, due to lack of knowledge or due to attitudes towards PrEP, this mode of prevention may be underutilized by people at risk and their providers. Our aim is to assess the baseline knowledge of, attitudes towards and practice of medical providers at Tufts Medical Center. Methods survey of 80 medical providers at Tufts Medical Center with a short questionnaire. Results The median age of the participants were 31 years old (IQR 28–34.5, range 22–71). 38.75% were male. Ethnicity were White (60%), Asian (20%), and others (20%). Fifty-five percent were Doctor of Medicine or Doctor of Osteopathic (MD/DO), 20% Physician assistant (PA), 8.75% Registered nurse (RN) and 7.5% were medical students. Other groups included Nurse practicioner (NP), medical assistant, research coordinator and PA student. Knowledge. Approximately two-third (67.5%) of study participants heard of PREP. In MD/DO group, 81.81% (36/44) heard about PREp. 46.26% responded correctly that PREP should be given daily. 68.75% answered correctly that Tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC; Truvada) is the standard regimen. Attitude. 31.81% of the MD/DO group were not comfortable prescribing PREP. Top three barriers perceived for prescribing PREP were “Not enough knowledge” 72.5%; “Lack of experience” 56.25% and “Not covered by insurance” 17.5%. Practice. Of 61 participants who are eligible to prescribe medications (MD/DO, PA, NP), 15.27% prescribed PREP prior to the survey. Over 75% would refer patients to infectious diseases or other providers to prescribe PREP. Conclusion There are some knowledge and practice gap of PREP. Most are not comfortable prescribing PREP thus will refer patients to infectious diseases. It is essential to promote knowledge and attitude about PREP in medical providers who have an important role in advising at-risk patients about PrEP which will lead to a better practice. Disclosures All authors: No reported disclosures.

/pdf/knowledge-attitude-and-practice-of-pre-exposure-prophylaxis-4hkt8jaswg.pdf

Knowledge, Attitude and Practice of Pre-exposure prophylaxis (PrEP) against HIV infection of medical providers at an academic center

Eikenella corrodens and group C streptococci.

A 32-Year-Old Woman With Miscarriage, Headache, Hepatitis, and Pulmonary Disease.

Bone marrow cryptococcosis has been rarely reported in the literature, and there are no established treatment guidelines specific to this AIDS-related complication. The recommended treatment for AIDS-related invasive fungal treatments include amphotericin B and flucytosine which are associated with an array of complications making optimal treatment recommendations difficult. This case presentation represents an example of a patient with newly diagnosed AIDS and bone marrow cryptococcosis, which was successfully managed with an antifungal regimen adjusted to her comorbidities.

/pdf/successful-management-of-cryptococcal-meningitis-and-bone-12uz2eqn23.pdf

David Stone

Papers

Managing Symptomatic Drug-Induced Liver Injury in HIV—Hepatitis C Virus—Coinfected Patients: A Role for Interferon

Knowledge, Attitude and Practice of Pre-exposure prophylaxis (PrEP) against HIV infection of medical providers at an academic center

Eikenella corrodens and group C streptococci.

A 32-Year-Old Woman With Miscarriage, Headache, Hepatitis, and Pulmonary Disease.

Successful Management of Cryptococcal Meningitis and Bone Marrow Infiltration in a Young HIV/AIDS Patient: A Case Report and Review of the Literature.