MedCompanion

Cytomegalovirus

CMV

Morphology: Enveloped, double-stranded DNA virus. Family Herpesviridae, subfamily Betaherpesvirinae. Largest of human herpesviruses; broad tissue tropism. Establishes latency in myeloid lineage; lifelong.

HerpesvirusVirus

Typical drugs

  1. #1Valganciclovir— **900 mg PO BID** for induction (mild-mod disease); 900 mg daily for maintenance / prophylaxis. Preferred outpatient.
  2. #2Ganciclovir— **5 mg/kg IV q12h** induction for severe disease (pneumonitis, encephalitis, hepatitis); maintenance 5 mg/kg daily.
  3. #3Foscarnet— **60 mg/kg q8h IV** for GCV-resistant CMV (UL97 mutation) or marrow-toxic patients.
  4. #4Acyclovir— Weak — NOT a CMV treatment drug. Some prophylactic role in HCT historically.

Empiric therapy when resistant

GCV resistance (UL97) → foscarnet 60 mg/kg q8h IV × induction. Multi-drug resistance (UL54) → maribavir 400 mg BID PO (newer, FDA 2021) — works against UL97 + UL54 mutants. Letermovir has no role in established disease (only HSCT prophylaxis).

Resistance mechanisms

  • altered-target

    UL97 mutations → GCV resistance

    Example: Most common resistance mechanism. Switch to foscarnet (UL97-independent). UL54 (DNA pol) mutations cause GCV + foscarnet + cidofovir cross-resistance — rare, salvage with maribavir / letermovir.

  • altered-target

    UL54 (DNA polymerase) mutations → multi-drug resistance

    Example: GCV + PFA + CDV resistance. Maribavir (newer, UL97 kinase inhibitor) effective even with UL97 + UL54 mutations.

Resistance notes

Resistance rises with prolonged exposure + suboptimal drug levels. Surveillance with viral load + sequencing if treatment failure.

Pearls

Transplant CMV management turns on D/R serostatus: D+/R− highest risk (50%+ without prophylaxis), R+ intermediate, D−/R− lowest. Prophylaxis (valganciclovir 900 mg daily × 100–200 days post-transplant) vs pre-emptive therapy (treat when PCR rises) — both acceptable; depends on center. Letermovir for CMV prophylaxis in HSCT — no myelosuppression, different mechanism. End-organ disease: pneumonitis (post-HSCT, often fatal), colitis, retinitis (HIV CD4 <50 — now rare with ART), hepatitis, encephalitis. Boards classic: 'owl-eye' inclusion bodies on biopsy. Congenital CMV is most common congenital infection; symptomatic newborns benefit from valganciclovir × 6 months (hearing + neurodev outcomes).

References