https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.12110

BK polyomavirus in solid organ transplantation.

Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules) This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic

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Host-directed therapies for bacterial and viral infections

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-6143.2012.04320.x

Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study

Reducing Immunosuppression Preserves Allograft Function in Presumptive and Definitive Polyomavirus-Associated Nephropathy

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-6143.2009.02904.x

BK Virus in Solid Organ Transplant Recipients

As new immunosuppressive agents are introduced to the market, clinicians are faced with the daunting task of sifting through the published literature to decide the value that the agent will add to their own practice. We often must extrapolate information provided through study in other solid-organ transplantation populations than our specific area of interest as we interpret the results and outcomes. With these challenges in mind, this compilation of published work for the newest mammalian target of rapamycin inhibitor everolimus (Certican; Novartis Pharmaceuticals, Hanover, NJ) (Zortress; Novartis Pharmaceuticals, Basel, Switzerland) is intended to provide a concise but thorough presentation of available literature so that the reader who may be unfamiliar with the agent can make their own judgment. Both Ovid and PubMed search engines were queried with a particular focus on high-impact articles noted in the Web of Science or Citation Index. Work described solely in abstract or case report form was excluded, as well as meta-analyses or those that were editorial or commentary in nature. Included were publications presented using the English language that described adult human subjects who received a heart, lung, kidney, or liver allograft. The goal of this strategy was to allow for the inclusion of pertinent literature in an unbiased fashion. Tables are provided that outline trial specific information, leaving a discussion of major outcomes to the text of the review.

A Comprehensive Review of Everolimus Clinical Reports: A New Mammalian Target of Rapamycin Inhibitor

BACKGROUND The specific role of different immunosuppressive agents as risk factors for BK virus nephropathy (BKN) has not been well studied METHODS In this case-control study, we examined the association of tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone with BKN in renal allograft recipients transplanted between 1997 and 2004 at our center who underwent biopsies for allograft dysfunction Drug levels or doses were recorded during the 3 months before the index biopsy Random effects logistic modeling was used for data analysis RESULTS There were 33 cases with BKN, biopsied at 164+/-28 months and 66 matched controls with biopsies at 215+/-21 months posttransplant (P=016) After adjusting for sex, race, retransplant status, diabetes, donor source, and induction agent, TAC blood level was associated with increased risk of BKN (odds ratio [OR] 13, 95% confidence interval [CI] 102-17, P=003), whereas MMF dose was not (OR 10, 95% CI 099-10, P=02) Moreover, prednisone dose was also found to be a significant risk factor for BKN (OR 122, 95% CI 104-14, P=002) CONCLUSIONS The results of this study show that BKN is associated with TAC level and prednisone dose and not with MMF dose This suggests that reducing TAC and prednisone dose and maintaining MMF may be a more appropriate initial approach for the treatment of BKN Further studies are needed to compare the efficacy and safety of this approach with the currently recommended one

Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: a case-control study.

Purpose of reviewAdverse events due to drug–drug interactions remain a challenge in the postsurgical care of transplant recipients. A combination of potent and selective immunosuppressive drugs, which have a narrow therapeutic index, with medications for the treatment of comorbidities such as dyslip

Drug interactions in transplant patients: what everyone should know.

Important of the field: BK virus has emerged as an important cause of graft dysfunction and failure in renal transplant recipients. Risk factors for BK virus nephropathy (BKN) are not well established, but evidence suggests that it is the result of a complex interplay between multiple donor- and recipient-related factors.Areas covered in this review: The purpose of this article is to review the current understanding on the effect of various immunosuppressive agents on BK viral replication and the results of different reported immunosuppression reduction protocols.What the reader will gain: The intensity of overall immunosuppression has been accepted as a major risk factor for the development of BKN. We review the data regarding the contribution of different anti-rejection agents to the risk of BK virus-induced graft injury.Take home message: Although reduction in immunosuppression on detection of BK viral replication appears to be the most successful means in preserving allograft function, data are emergi...

Immunosuppressive agents as risk factors for BK virus nephropathy: an overview and update.

Background Protease inhibitors (PI) pose a challenge post-transplant due to significant drug interactions with calcineurin inhibitors, prompting many clinicians to convert patients to non-interacting regimens prior to transplant. The purpose of this study was to examine the impact of PI-based regimens on graft outcomes in HIV-infected renal transplant recipients. Methods In this retrospective cohort study, 50 HIV-infected renal allograft recipients (27 receiving a PI regimen, 23 receiving a non-PI regimen) transplanted between 2003-2015 were analyzed. Results Cumulative rejection rates at 12 and 36 months were 41% and 54% in the PI group vs 52% and 86% in the non-PI group. At last follow-up, the overall risk of acute rejection in the PI group was 46% lower compared with the non-PI cohort (P = 0.12). Patients who received a PI-based regimen had significantly reduced graft failure rates (P = 0.027). There was no difference between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies, despite longer follow-up time in the PI group. Conclusions Our study suggests that PI-based antiretroviral therapy regimens are associated with improved graft survival and that patients can achieve adequate outcomes on a PI-based regimen when necessary. Due to study limitations, further studies are needed to determine the optimal immunosuppression/antiretroviral therapy regimen post-transplant.

Wana Manitpisitkul

Papers

A Comprehensive Review of Everolimus Clinical Reports: A New Mammalian Target of Rapamycin Inhibitor

Maintenance immunosuppressive agents as risk factors for BK virus nephropathy: a case-control study.

Drug interactions in transplant patients: what everyone should know.

Immunosuppressive agents as risk factors for BK virus nephropathy: an overview and update.

Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected recipients.