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Resistance to letermovir occurred with ‘unnerving frequency’ while treating active CMV
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According to a recent study, letermovir led to clinical improvements in patients when used as salvage treatment in organ transplant recipients with ganciclovir-resistant cytomegalovirus retinitis. However, according to researchers, some patients failed to maintain virologic suppression, and resistance to letermovir eventually developed.
“[Cytomegalovirus (CMV)] retinitis is a vision-threatening infection that is difficult to treat even when effective antivirals are available. Unfortunately, resistance to first-line antivirals is relatively common — as are therapy-limiting adverse drug effects among currently available alternative agents,” Nicholas Turner, MD, fellow of the division of infectious disease at the Duke University Medical Center, told Infectious Disease News. “As a result, patients are often left with a small number of relatively toxic drugs for treatment options. While letermovir has proven extremely safe and effective in prophylaxis studies, experience in the treatment of active infection remains limited.”
Researchers analyzed clinical data from adult patients at a tertiary care hospital in North Carolina who initiated letermovir for treatment of CMV between November 2017 and April 2018. According to the study, four patients received letermovir for treatment of ganciclovir-resistant CMV disease after therapy with ganciclovir/valganciclovir failed and nephrotoxicity from foscarnet developed. Additionally, researchers noted that the patients had genotypically proven resistance to ganciclovir.
Results of the study showed that letermovir was well tolerated, and all four patients had clinical improvement with resolution of retinitis. However, three patients failed to achieve sustained virologic suppression, and two of these patients developed genotypically confirmed resistance to letermovir while on therapy.
According to Turner, the biggest takeaway from the study is that resistance to letermovir occurred with “unnerving frequency.” Turner urged caution for anyone considering letermovir as therapy for active CMV infection.
“While a case series alone cannot offer any definitive answers, our study should remind us that prophylaxis and treatment remain two very different indications. Even if an agent proves effective at prophylaxis, the hurdle for resistance may be very different in the setting of active infection,” Turner said. “We remain in need of more tolerable and effective options for treating CMV, as well as strategies to mitigate the development of antiviral resistance while on therapy.” – by Caitlyn Stulpin
Disclosures: The authors report no relevant financial disclosures.
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