Viral Infections and Antiviral Therapy
Core concepts
Understand the major antiviral classes and their targets: acyclovir/valacyclovir (HSV/VZV thymidine kinase, renal dosing), ganciclovir/valganciclovir (CMV UL97 kinase, myelosuppression), foscarnet (pyrophosphate analog, no kinase required-use for resistant CMV/HSV; nephrotoxic, electrolyte wasting), cidofovir (nephrotoxic, requires probenecid), oseltamivir/baloxavir (influenza; baloxavir is single-dose cap-dependent endonuclease inhibitor), and remdesivir (RNA-dependent RNA polymerase).
Must-know syndromes
HSV encephalitis (temporal lobe; start IV acyclovir empirically), VZV (acyclovir; consider VZIG post-exposure in pregnancy/immunocompromised), CMV (retinitis in AIDS, colitis in transplant; valganciclovir), influenza (oseltamivir within 48 hours, but treat severe/hospitalized regardless of timing), RSV (supportive; ribavirin in select immunocompromised), and hepatitis B/C (tenofovir/entecavir; direct-acting antivirals for HCV).
Traps
Acyclovir can cause crystal nephropathy-hydrate. Ganciclovir causes neutropenia and thrombocytopenia. Foscarnet causes renal failure and hypocalcemia/hypomagnesemia. Don't use baloxavir in pregnancy or severe immunocompromise. Influenza antiviral resistance: oseltamivir-resistant H275Y needs peramivir or baloxavir. Distinguish HSV and VZV reactivation from drug eruptions.
Worked rule of thumb
In a transplant patient with CMV viremia and neutropenia, valganciclovir may be contraindicated; foscarnet or cidofovir (with probenecid and hydration) may be preferred. Confirm resistance with genotyping before switching.