Human immunodeficiency virus and solid organ transplantation: a 15-year retrospective audit at a tertiary Australian transplant centre.

BACKGROUND: The incidence of end-stage organ disease in people living with human immunodeficiency virus (HIV) (PLWH) is increasing, as people live longer due to potent, tolerable antiretroviral therapy (ART). Consequently, the number of PLWH who would benefit from solid organ transplant (SOT) is rising. The SOT experience in PLWH in Australia remains limited. Aim To retrospectively review the outcomes for SOT in PLWH at our service, in Victoria, Australia. METHODS: A retrospective cohort study of PLWH undergoing SOT over a 15-year period was performed. Adult PLWH age >18 years were eligible and identified from the Victorian HIV Service database. Descriptive statistics were used to summarise baseline demographics and clinical data, and outcomes following SOT. RESULTS: Nine virologically suppressed PLWH underwent SOT from HIV-negative donors (five kidneys, two livers and two bilateral sequential lung transplants). All patients were male, with a median age of 57.3 years (interquartile range (IQR) = 54.3-60.1) and CD4 count of 485 (IQR = 342-835) at transplantation, and comorbidities were common at baseline. After a median follow up of 3.9 years (IQR = 2.7-7.6), 8 (89%) patents were alive, 7 (78%) had functioning grafts, although 5 (56%) experienced organ rejection. Infections were common. Two patients required modification to their ART due to significant drug-drug interactions prior to transplant, while 5 (56%) had modifications post-SOT. No patients experienced HIV virologic failure. CONCLUSION: PLWH with end-stage organ disease experience good clinical and functional outcomes and should be considered for SOT where indicated. However, multidisciplinary planning and care is essential to optimise care in this patient group.

The impact of immune checkpoint therapy on the latent reservoir in HIV-infected individuals with cancer on antiretroviral therapy.

OBJECTIVE: The aim of this study was to quantify HIV-specific immunological and virological changes in people with HIV (PWH) on antiretroviral therapy (ART) with malignancy who received immune checkpoint blockade (ICB). DESIGN: An observational cohort study. METHODS: Blood samples were collected before and after four cycles of ICB in HIV-positive adults on ART. Virological assessments performed on CD4+ T cells included cell-associated unspliced HIV RNA, cell-associated HIV DNA, Tat/rev-induced limiting dilution assay (TILDA) and plasma HIV RNA using a single copy assay (SCA). Flow cytometry was used to assess the frequency of precursor exhausted T cells (Tpex) and exhausted T cells (Tex), and Gag-specific CD4+ and CD8+ T cells positive for IFN-γ, TNF-α or CD107a by intracellular cytokine staining (ICS). RESULTS: Participant (P)1 received avelumab (anti-PD-L1) for Merkel cell carcinoma. P2 and P3 received ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) for metastatic melanoma. An increase in CA-US RNA following each infusion was noted in all three participants. There were no consistent changes in HIV DNA or the proportion of cells with inducible MS HIV RNA. P2 demonstrated a striking increase in the frequency of gag-specific central and effector memory CD8+ T cells producing IFN-γ, TNF-α and CD107a following anti-PD1 and anti-CTLA-4. The frequency of CD8+ Tpex cells pre-ICB was also highest in this participant. CONCLUSION: In three PWH with cancer on ART, we found that ICB activated latent HIV and enhanced HIV-specific T cell function but with considerable variation.

Barriers and strategies to achieve a cure for HIV.

9 years since the report of a cure for HIV after C-C chemokine receptor type 5 Δ32 stem cell transplantation, no other case of HIV cure has been reported, despite much research. However, substantial progress has been made in understanding the biology of the latent HIV reservoir, and in measuring the amount of virus that persists after antiretroviral therapy (ART) with increasingly sophisticated approaches. This knowledge is being translated into a long pipeline of clinical trials seeking to reduce viral persistence in participants on suppressive treatment and ultimately to allow safe cessation of ART. In this Review, we discuss the main barriers preventing the development of an HIV cure, methods used to measure HIV persistence in individuals on ART, clinical strategies that aim to cure HIV, and future directions for studies in the field of HIV cure research.

Epstein-Barr virus encephalitis in solid organ transplantation.

Epstein-Barr virus (EBV) is typically associated with post transplant lymphoproliferative disease (PTLD) after solid organ and stem cell transplantation. However, it is rarely associated with neurological complications. We report a case of severe encephalitis complicating primary EBV infection six months post renal transplantation, and review the literature on EBV encephalitis in solid organ transplantation in adults. A 55-year-old male presented 6 months post cadaveric renal transplant with headache, fever and confusion. Neuroimaging was unremarkable, but an electroencephalogram was consistent with diffuse encephalopathy. EBV DNA was detected in both cerebrospinal fluid (13,177 copies/ml), and plasma (14,166 copies/ml). Management included reduction of immunosuppression, intravenous ganciclovir and intravenous immunoglobulin, and resulted in a reduction in EBV viral load in both plasma and cerebrospinal fluid. The patient made a full recovery with no long-term neurological deficits and preservation of the graft. This case highlights the importance of knowing donor and recipient EBV serostatus at time of transplant, and closely monitoring EBV DNA when there is a mismatch. Ganciclovir or valganciclovir prophylaxis has also been shown to reduce the incidence of primary EBV infection in renal transplantation in these recipients. Treatment options for EBV infection post-transplant include reduction of immunosuppression, antiviral therapy, IVIg, and monoclonal antibody therapy directed toward infected B lymphocytes.

Surveillance of life-long antibiotics: a review of antibiotic prescribing practices in an Australian Healthcare Network.

BACKGROUND: The rise of antimicrobial use in the twentieth century has significantly reduced morbidity due to infection, however it has also brought with it the rise of increasing resistance. Some patients are on prolonged, if not "life-long" course of antibiotics. The reasons for this are varied, and include non-infectious indications. We aimed to study the characteristics of this potential source of antibiotic resistance, by exploring the antibiotic dispensing practices and describing the population of patients on long-term antibiotic therapy. METHODS: A retrospective cross-sectional study of antibiotic dispensing records was performed at a large university hospital-based healthcare network in Melbourne, Australia. Outpatient prescriptions were extracted from the hospital pharmacy database over a 6 month period in 2014. Medical records of these patients were reviewed to determine the indication for prescription, including microbiology, the intended duration, and the prescribing unit. A descriptive analysis was performed on this data. RESULTS: 66,127 dispensing episodes were reviewed. 202 patients were found to have been prescribed 1 or more antibiotics with an intended duration of 1 year or longer. 69/202 (34%) of these patients were prescribed prolonged antibiotics for primary prophylaxis in the setting of immunosuppression. 43/202 (21%) patients were prescribed long-term suppressive antibiotics for infections of thought incurable (e.g. vascular graft infections), and 34/43 (79%) were prescribed by Infectious Diseases doctors. 66/202 (33%) patients with cystic fibrosis were prescribed prolonged courses of macrolides or fluoroquinolones, by respiratory physicians. There was great heterogeneity noted in indications for prolonged antibiotic courses, as well as antibiotic agents utilised. CONCLUSION: Our study found that that continuous antibiotic therapy represented only a small proportion of overall antibiotic prescribing at our health network. Prolonged courses of antibiotics were used mainly to suppress infections thought incurable, but also as primary and secondary prophylaxis and as anti-inflammatory agents. More research is needed to understand the impact of long-term antibiotic consumption on both patients and microbial ecology.

Human Wound Infection with Mannheimia glucosida following Lamb Bite.

Mannheimia spp. are veterinary pathogens that can cause mastitis and pneumonia in domestic cattle and sheep. While Mannheimia glucosida can be found as normal flora in oral and respiratory mucosa in sheep, there have been no reported cases of human infection with this organism.