Complex considerations - Fever and pancytopenia after solid organ transplantation.

This case describes a 42-year-old man who underwent kidney transplantation and developed fevers, pancytopenia, and elevated liver function tests starting on post-operative day 9. An extensive microbiologic and molecular workup was performed, ultimately leading to a diagnosis of donor-derived toxoplasmosis with associated hemophagocytic lymphohistiocytosis in the recipient. This case highlights the potential for post-transplant toxoplasmosis in high-risk mismatch (D+/R-) recipients, as well as the role of Toxoplasma-targeted prophylaxis in such patients.

Early steps to kidney transplantation among persons with HIV and end-stage renal disease in ESRD network 6.

INTRODUCTION: End-stage renal disease is a significant cause of morbidity and mortality in persons with HIV (PWH). Limited data exist on access to kidney transplantation for this population. METHODS: A dataset inclusive of incident dialysis patients between 2012 and 2016 with follow-up through December 2017 that identifies PWH and the general dialysis population of Network 6 (Georgia, North Carolina, South Carolina) was created through merging the United States Renal Data System with the southeastern early transplant access registry. Early steps to kidney transplantation and patient and dialysis facility-level characteristics that serve as barriers to transplantation were described. RESULTS: Twenty-three thousand four hundred fourteen patients were identified; 469 were PWH. Compared to non-HIV individuals, PWH were younger (49 vs. 58 years, p < 0.001), predominantly Black (87% vs. 56% p < 0.001) and male (72% vs. 56% p < 0.001). PWH were less likely to be referred to kidney transplant within 1 year of starting dialysis (36% vs. 41% p < 0.001) and waitlisted within 1 year of evaluation-start (14% vs. 30%, p = 0.05). PWH (vs. non-PWH) waited longer for referral, evaluation-start, and waitlisting and in multivariable analysis; HIV positivity was associated with a lower probability of referral (hazard ratios [HR]: 0.70; 95% confidence intervals [CIs]: 0.62-0.80), evaluation (HR 0.66; 95% CI: 0.55-0.80), and waitlisting (HR 0.29; 95% CI: 0.20-0.41). CONCLUSIONS: Targeted interventions are needed to improve access to kidney transplants, particularly in waitlisting, for PWH.

Clinical characteristics and outcomes of toxoplasmosis among transplant recipients at two US academic medical centers.

Toxoplasma gondii can cause severe opportunistic infection in immunocompromised individuals, but diagnosis is often delayed. We conducted a retrospective review of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients with toxoplasmosis between 2002 and 2018 at two large US academic transplant centers. Patients were identified by ICD-9 or ICD-10 toxoplasmosis codes, positive Toxoplasma polymerase chain reaction test result, or pathologic diagnosis. Data were collected regarding transplant type, time from transplant to toxoplasmosis diagnosis, clinical and radiographic features, and mortality at 30 and 90 days. Twenty patients were identified: 10 HSCT recipients (80% allogeneic HSCT) and 10 SOT recipients (60% deceased donor renal transplants). Rejection among SOT recipients (70%) and graft-versus-host disease (GVHD) prophylaxis among HSCT recipients (50%) were frequent. Median time from transplant to toxoplasmosis diagnosis was longer for SOT than HSCT (1385 vs. 5 days, P-value .002). Clinical manifestations most commonly were encephalitis (65%), respiratory failure (40%), renal failure (40%), and distributive shock (40%). Cohort 30-day mortality was 45%, and 90-day mortality was 55%. Diagnosis was postmortem in 25% of the cohort. Further evaluation of toxoplasmosis screening is needed for noncardiac SOT recipients, HSCT recipients with GVHD, and periods of increased net immunosuppression.

Hepatitis C Care Continuum in a Human Immunodeficiency Virus (HIV) Positive Cohort: Data From the HIV Atlanta Veterans Affairs Cohort Study.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection is associated with accelerated progression to cirrhosis, end-stage liver disease, and liver-associated death. It is fortunate that curative direct-acting antivirals for the treatment of HCV are widely available in the VA healthcare system. We attempted to identify, evaluate, and treat all HIV/HCV-coinfected persons at the Atlanta VA Healthcare System. METHODS: Human immunodeficiency virus/HCV-coinfected persons at Atlanta VA between 2015 and 2018 were identified using the HIV Atlanta Veterans Affairs Cohort Study and Hepatitis C VA Clinical Case Registry. Retrospective reviews of each electronic medical record were conducted by the hepatitis C clinical team for validation. The primary end point was achieving sustained virologic response. RESULTS: One hundred thirty-eight veterans with HIV and hepatitis C viremia were identified. One hundred twenty-five (90%) were evaluated for treatment and 113 (91%) were initiated on direct-acting antiviral therapy. Median age at initiation of treatment was 60 years and the majority were black race (90%). Genotype 1a was most common (70%) and 41% had compensated cirrhosis. One hundred eight completed treatment and 96% achieved sustained virologic response. Six veterans had virologic relapse; 4 had treatment-emergent resistance mutations in the NS5a gene. Mean CD4 was 580 cells/mm3 with HIV viral suppression in 82% of the cohort. In those not treated, unstable housing (25%), active substance use (31%), and psychiatric conditions (42%) were identified barriers to care. CONCLUSIONS: Through a concerted, systematic effort, over 80% of HIV/hepatitis C persons in the Atlanta VA have been initiated on treatment for hepatitis C, 96% of which have been cured.

Metabolic Syndrome in HIV/HCV Co-infected Patients.

PURPOSE OF REVIEW: We review the scope and burden of metabolic syndrome in HIV/HCV co-infected patients, risk factors and potential mechanisms driving the increased cardio-metabolic risk in this population, and discuss relevant clinical considerations for management in the era of highly effective antiretroviral therapy (ART) and curative anti-HCV direct-acting antivirals. RECENT FINDINGS: HIV/HCV co-infected patients are at elevated risk of metabolic syndrome, attributed to (1) patient-specific factors, (2) viral-mediated effects, and (3) ART exposure. Risk factors for cardio-metabolic disorders are common in this population and include poor socioeconomic conditions, substance use, cardiovascular comorbidities, and liver/kidney disease. Chronic HIV/HCV infection induces an inflammatory and immune activated state in the host leading to alterations in glucose and lipid metabolism. Selection of life-saving ART must carefully consider the differential metabolic risk associated with each drug class and agent, such as dyslipidemia, hyperglycemia and insulin resistance, weight gain and hypertension. Emerging evidence supports metabolic derangements in chronic HCV may be improved by viral eradication with direct-acting antivirals, however, additional study in HIV/HCV co-infected patients is needed. SUMMARY: Future research programs should aim to better characterize metabolic syndrome in HIV/HCV co-infected patients with the goal of improved screening, treatment and prevention.