Refractory and/or resistant HSV infections in immunocompromised patients may be challenging to manage with limited treatment options1
The HSV treatment landscape has changed little in recent decades, relying on nucleoside analogues for prophylaxis and first-line treatment while resorting to drugs, such as foscarnet, for refractory and/or resistant cases.1-6
Hover over each card to learn more.
Tap on a card to learn more.
Common treatment modifications after inadequate response to nucleoside analogue therapy, such as acyclovir and valacyclovir7
Dose titration7- Switching to another nucleoside analogue7
- Route of administration changes7
In acyclovir-resistant HSV, within-class treatment modifications are likely to have cross-resistance.9
Challenges of repeated nucleoside analogue use4-6,8
- Associated with nephrotoxicity, gastrointestinal intolerance, neurotoxicity, and higher rates of resistance in immunocompromised patients4,10
- Complicated, long-term dosing may lead to issues with adherence4-6,8
Nucleotide analogues, such as cidofovir, and DNA polymerase inhibitors, such as foscarnet, may be effective but have clinical limitations1,4-6
- May require inpatient administration4,11
- Frequent lab monitoring4,11
- Carry Black Box warnings and are associated with high rates of adverse events4,11-14
In one study, foscarnet was associated with frequent electrolyte abnormalities, renal function abnormalities, and a discontinuation rate of 30.3%.14
"As the current alternative therapy for R/R HSV infection is limited to a few medications with significant toxic effects, such as FOS, investigating new treatment options is crucial, especially for immunocompromised patients."1
— Chemaly RF et al. Clin Infect Dis. 2025.
FAQs
Delayed recognition of refractory and/or resistant HSV may delay the initiation of appropriate therapy, which subsequently increases the risk of severe and/or disseminated infections. Early recognition may help guide timely evaluation and appropriate management.1
Although nucleoside analogues remain the standard first-line treatment for most HSV infections, acyclovir resistance can occur, particularly in immunocompromised patients. Alternative therapies for refractory and/or resistant disease may require intravenous administration, inpatient care, or laboratory monitoring, or they may carry the potential for significant toxicities, creating additional treatment challenges.1,11
FOS, foscarnet; HSV, herpes simplex virus; R/R, refractory and/or resistant.
References: 1. Chemaly RF et al. Clin Infect Dis. 2025;81(3):593-601. doi:10.1093/cid/ciae638 2. Birkmann A et al. J Med Chem. 2022;65(20):13614-13628. doi:10.1021/acs.jmedchem.2c00668 3. National Center for Biotechnology Information. PubChem Compound Summary for CID 135398742, Valacyclovir. PubChem. National Library of Medicine. Accessed August 7, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/valacyclovir 4. National Institutes of Health. Updated May 27, 2026. Accessed July 17, 2026. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new 5. Lee DH et al. Clin Transplant. 2019;33(9):e13526. doi:10.1111/ctr.13526 6. Workowski KA et al. MMWR Recomm Rep. 2021;70(4):1-187. doi:10.15585/mmwr.rr7004a1 7. Chemaly RF. Poster presented at: ESCMID Global 2026; April 17-21, 2026; Munich, Germany. 8. Gupta R et al. Lancet. 2007;370(9605):2127-2137. doi:10.1016/S0140-6736(07)61908-4 9. Schalkwijk HH et al. Biochem Pharmacol. 2022;206:115322. doi:10.1016/j.bcp.2022.115322 10. Birkmann A et al. Antiviral Res. 2025;237:106152. doi:10.1016/j.antiviral.2025.106152 11. Hammond SP et al. Open Forum Infect Dis. 2024;11(3):ofae046. doi:10.1093/ofid/ofae046 12. Cidofovir injection, USP [prescribing information]. 13. FOSCAVIR (foscarnet sodium) injection [prescribing information]. 14. Papanicolaou GA et al. Open Forum Infect Dis. 2026;13(7):ofag377. doi:10.1093/ofid/ofag377