Samantha Troy, PharmD candidate

Cytomegalovirus (CMV) is a common pathogen post-transplant. CMV-seronegative patients lack personal immunity; if they receive organ transplants from seropositive donors, the risk for infection from the transplanted organ is high. Antiviral prophylaxis with valganciclovir for at least 3 months is the current standard for prevention of CMV infections post liver transplant.

An alternative method is preemptive therapy: starting antivirals once surveillance testing detects early asymptomatic CMV viremia. Now, a study suggests using preemptive therapy may lower the incidence of CMV disease over 12 months, compared to antiviral prophylaxis in this high-risk population.

A research team from Pittsburgh randomized 205 patients with CMV seronegative liver transplant who received grafts from CMV seropositive donors in a prospective multicenter trial at 6 United States transplant centers. The study’s 2 arms compared prophylaxis to preemptive therapy 1:1. The primary outcome measure was the incidence of CMV disease by 12 months post-transplant.

These researchers monitored patients in the preemptive therapy arm with weekly testing for CMV viremia for 100 days. If they detected any level of viremia, they started valganciclovir 900 mg by mouth twice daily until the patient had 2 consecutive negative PCR tests 1 week apart.

The patients in the comparator arm received antiviral prophylaxis with valganciclovir 900 mg daily for 100 days after transplant, with no monitoring.

The incidence of CMV disease at 12 months was significantly lower in patients who received preemptive therapy (9%) than in the antiviral prophylaxis arm (19%).

Preemptive therapy in liver transplant recipients at high-risk for contracting CMV may be a viable approach. Clinicians cannot extrapolate these results to other types of organ transplants due to biologic differences, and differences in the intensity of immunosuppressive therapies. Additionally, preemptive therapy requires weekly monitoring and timely initiation of antiviral therapy; some transplant programs may be unable to provide these components.

The authors acknowledge that further research is needed to replicate their findings and assess long-term outcomes.

 is a 2021 PharmD Candidate at the University of Connecticut in Storrs.

Singh N, Winston DJ, Razonable RR, et al. Effect of preemptive therapy vs antiviral prophylaxis on cytomegalovirus disease in seronegative liver transplant recipients with seropositive donors: a randomized clinical trial. 

 2020;323(14):1378—1387. doi:10.1001/jama.2020.3138

Articles

Cytomegalovirus is a common pathogen post-transplant.

Cytomegalovirus Disease Prevention in High Risk Liver Transplant Patients: Preemptive Therapy or Prophylaxis?

The field of pharmacy is making major advancements, thanks to the increase in pharmacogenomics research. Studying individuals’ genomes can help influence how different medications work for a patient, avoid harmful adverse drug reactions, and allow scientists to develop personalized medicines for patients with a wide range of diseases and disorders.

Researchers from universities around the world conducted a meta-analysis of genome-wide association studies to explore genes that could be potential targets for pharmacologic therapy of Attention-Deficit Hyperactivity Disorder (ADHD), and its comorbidities. The comorbidities included in the study fell into 3 categories: cardiovascular, immune, and neuropsychiatric.

The study results were published in the journal 

Researchers were able to identify 9 genes significantly associated with ADHD. Five of the 9 genes are encoded for drug targets that are currently being explored in clinical trials. Although these clinical trials are studying drugs for other indications, including autoimmune diseases, and Parkinson disease, results will be useful for ADHD since the drugs act on the same genes.

These researchers indicate that current pharmacological treatments for ADHD deliver effective symptomatic relief for some patients. The FDA-approved medications target a total of 23 genes. However, none of these genes are significantly associated with ADHD. Thus, there is a mismatch between current treatment and genes significantly associated with ADHD. Research is needed to determine if targeting these genes will improve symptoms or change the trajectory of the condition.

The mechanisms of action for FDA-approved drugs that treat ADHD are still unknown. Because this disorder is complex, additional research is needed to identify its underlying pathways, and potential new drug targets.

One gene found to be associated with ADHD encodes a voltage-dependent potassium channel. Dalfampridine is a nonspecific potassium channel blocker that is currently used to treat symptoms of multiple sclerosis, and other neurologic disorders. It targets the same gene as the one associated with ADHD. This medication may be used in the future to enhance cognitive skills in patients with ADHD. 

Although treatment options have expanded in recent years, there are future possibilities as researchers conduct more pharmacogenomics research. Analyzing the druggable genome of other disorders will give insight into new treatment options. New drug targets and repurposing of drugs will be invaluable for the treatment of ADHD, and many other disorders.

Hegvik T-A, Waløen K, Pandey SK, Faraone SV, Haavik J, Zayats T. Druggable genome in attention deficit/hyperactivity disorder and its co-morbid conditions. New avenues for treatment. 

Studying individuals’ genomes can help influence how different medications work for a patient, avoid harmful adverse drug reactions, and allow scientists to develop personalized medicines for patients with a wide range of diseases and disorders.