When should antiviral prophylaxis be started in solid‑organ transplant recipients (kidney, liver, heart, lung) based on donor and recipient serostatus for herpes simplex virus, varicella‑zoster virus, cytomegalovirus, hepatitis B virus, and hepatitis C virus?

When to Start Antivirals in Solid Organ Transplantation

Antiviral prophylaxis should be initiated immediately at the time of transplantation for CMV-at-risk recipients (all except D-/R-), with oral valganciclovir or ganciclovir continued for at least 3 months in kidney transplant recipients and extended to 6-12 months in higher-risk populations such as lung transplant recipients. 1, 2

Cytomegalovirus (CMV) Prophylaxis

Timing and Duration by Serostatus

Universal prophylaxis (except D-/R-):

• Start immediately post-transplant with oral valganciclovir 900 mg daily (dose-adjusted for renal function) or oral ganciclovir 1, 2
• Minimum duration: 3 months for standard-risk kidney transplant recipients (D+/R+ or D-/R+) 1
• Extended duration: 6-12 months for high-risk recipients (D+/R-) in kidney transplantation, with evidence supporting up to 12 months in lung transplant recipients 2, 3

The KDIGO guidelines provide a Grade 1B recommendation for this approach, representing strong evidence that prophylaxis reduces CMV disease, all-cause mortality, and CMV-related death 1, 2. A 2024 Cochrane review confirmed high-certainty evidence that prophylaxis reduces CMV disease by 58% (RR 0.42) and all-cause death by 37% (RR 0.63) 2.

Additional Prophylaxis After T-Cell Depleting Therapy

• Start immediately upon initiation of T-cell depleting antibody treatment for acute rejection 4
• Continue for 6 weeks after completion of antibody therapy, regardless of baseline CMV serostatus 1, 4
• Use valganciclovir 900 mg daily (adjusted for renal function) 4

This represents a Grade 1C recommendation from KDIGO, acknowledging that even CMV R+ patients benefit from prophylaxis after T-cell depletion 1, 4.

Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV) Prophylaxis

HSV Prophylaxis Timing

For patients with prior HSV history:

• Start at transplantation with acyclovir, valacyclovir, or famciclovir 1, 5
• Continue during neutropenia in autologous HSCT recipients 1
• Continue for at least 30 days post-transplant in standard solid organ transplant recipients 1

VZV Prophylaxis Timing

For allogeneic HSCT recipients:

• Start at transplantation with acyclovir, valacyclovir, or famciclovir 1
• Continue for at least 1 year post-transplant 1

The evidence demonstrates that aciclovir and valaciclovir are highly effective for preventing HSV and VZV infections in transplant recipients 5.

Hepatitis B Virus (HBV) Prophylaxis

For HBV-Positive Recipients

Start immediately at transplantation with nucleos(t)ide analogues (entecavir or tenofovir preferred) 1

• Continue indefinitely post-transplant to prevent reactivation 1
• HBV immunoglobulin may be added in liver transplant recipients, though newer regimens use lower doses or omit it entirely 3

For HBV-Negative Recipients Receiving HBV-Positive Organs

Start prophylaxis at transplantation and continue long-term 1

Hepatitis C Virus (HCV) Management

Timing of Antiviral Treatment (Not Prophylaxis)

Do NOT start antivirals immediately post-transplant for HCV-positive recipients 1

• Wait at least 6 months post-transplant before initiating HCV treatment 1
• Require histological confirmation of chronic hepatitis C before treatment 1
• Exception: Start as soon as possible if advanced fibrosis or portal hypertension develops, as these predict rapid progression 1

This delay is critical because early post-transplant patients are heavily immunosuppressed and incompletely recovered from surgery, resulting in high probability of drug intolerance and potential allograft rejection with interferon-based regimens 1.

Critical Monitoring Requirements

CMV Surveillance

• Weekly monitoring with quantitative plasma NAT or pp65 antigenemia during active CMV disease or high-risk periods 1, 6
• Plasma viral load is the preferred method over antigenemia testing 6

BK Virus Surveillance (Kidney Transplant)

• Monthly screening for the first 3-6 months post-transplant using quantitative plasma NAT 1, 7, 6
• Every 3 months through the end of the first post-transplant year 1, 7
• Additional screening after treatment for acute rejection, as augmented immunosuppression increases BK virus reactivation risk 7

Common Pitfalls to Avoid

Do not omit CMV prophylaxis based on serostatus alone - even CMV R+ patients benefit from prophylaxis, and approximately 25% of all transplant recipients will develop CMV infection regardless of D/R status 4, 8

Do not delay prophylaxis initiation - antiviral prophylaxis must start immediately at transplantation or at the time of T-cell depleting therapy to be effective 1, 4

Do not use shorter durations in high-risk populations - extended duration prophylaxis (6-12 months) significantly reduces CMV disease in D+/R- recipients and lung transplant patients compared to 3-month regimens 2, 3

Do not start HCV treatment too early - the 6-month waiting period post-liver transplant is essential to avoid complications from incomplete surgical recovery and heavy immunosuppression 1

Do not rely on urine BK testing alone - plasma viral load is more specific for nephropathy risk and should guide management decisions 7, 6

Do not forget prophylaxis after rejection treatment - the 6-week course of valganciclovir following T-cell depleting antibodies is mandatory regardless of baseline serostatus 1, 4