Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients

Abstract

Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be challenging because these drugs have a narrow therapeutic window and show significant pharmacokinetic variability. Above that, immunocompromised patients have various comorbidities like impaired renal function and are exposed to polypharmacy. This scoping review discusses the current pharmacokinetic (PK) and pharmacodynamic (PD) knowledge of antiviral drugs for HSV and CMV treatment in immunocompromised patients. HSV and CMV treatment guidelines are discussed, and multiple treatment interventions are proposed: early detection of drug resistance; optimization of dose to target concentration by therapeutic drug monitoring (TDM) of nucleoside analogs; the introduction of new antiviral drugs; alternation between compounds with different toxicity profiles; and combinations of synergistic antiviral drugs. This research will also serve as guidance for future research, which should focus on prospective evaluation of the benefit of each of these interventions in randomized controlled trials.

Development and Validation of an HPLC-UV Method for the Quantification of Acyclovir and Ganciclovir in the Plasma of Pediatric Immunocompromised Patients

“…To date, the gold standard prophylaxis and treatment of HSV and CMV infections consist of the antivirals acyclovir and ganciclovir. These agents are nucleoside analogues that, once converted in their corresponding triphosphates by cellular kinases, are able to incorporate themselves into viral DNA and to disrupt DNA synthesis, thus inhibiting viral replication [ 3 ].…”

Identification of Novel Drug Targets and Immune Response Biomarkers in HCMV-Infected Hosts

“…They often have CMV mononucleosis which can lead to several symptoms including fatigue, muscle aches, headache, sore throat, and swollen lymph nodes (Ishii et al, 2019;Pakkiyaretnam et al, 2020). Individuals having congenital (present at birth) HCMV means that the virus passed from mother to the fetus and infants who got infected shortly after birth merely through breastfeeding can experience symptoms related to a number of diseases including anemia, jaundice, hepatomegaly, microcephaly, hearing loss, seizures, rash (Lin et The available antiviral therapies against HCMV-related diseases include ganciclovir, foscarnet, cidofovir, letermovir, maribavir, and other antibody therapies (Huntjens et al, 2023). Nanotechnology, an in vitro antiviral therapy that serves as a low-cost procedure against HCMV also emerged.…”

“…Foscarnet and cidofovir both are used as second-line drugs in the instance of resistance to ganciclovir (Perera et al, 2021). Foscarnet reversibly inhibits viral DNA polymerases (Huntjens et al, 2023). Induction therapy with foscarnet helped CMV retinitis patients and their optical symptoms initially diminished but recurred soon after the treatment stopped (Heiden et al, 2019).…”

Acute Kidney Injury in the ICU during Ganciclovir Treatment, an Observational Study

“…As a group, antiviral drugs are associated with crystal nephropathy [4]. Moreover, ICU patients are at risk for multiorgan failure (MOF), and MOF has been identified as a risk factor for ganciclovir-induced toxicity [5]. Ganciclovir has a narrow therapeutic window [6].…”