Antiviral Drugs

Antiviral drugs inhibit viral replication by acting on virus-specific enzymes or entry steps, so they act only while the virus is replicating and do not eradicate latent virus. Most are nucleoside or nucleotide analogues that require phosphorylation and terminate chain elongation. Their clinical value depends on early treatment, so timing is as important as drug choice.

Targets by group.

• Herpesviruses: aciclovir, valaciclovir and famciclovir inhibit viral DNA polymerase after activation by viral thymidine kinase. Ganciclovir, valganciclovir, foscarnet, cidofovir and letermovir act on cytomegalovirus.
• Influenza: oseltamivir and zanamivir inhibit neuraminidase; baloxavir inhibits cap-dependent endonuclease.
• HIV: reverse transcriptase, protease, integrase and entry inhibitors.
• Hepatitis B: tenofovir and entecavir inhibit viral polymerase.
• Hepatitis C: direct-acting agents inhibit NS3/4A protease, NS5A and NS5B polymerase.
• Coronavirus: remdesivir (RNA polymerase) and nirmatrelvir with ritonavir (protease).

• Aciclovir: poor oral bioavailability (about 20%); valaciclovir is a prodrug with about 3 to 5 times higher bioavailability.
• Ganciclovir: marrow toxic; valganciclovir is oral; foscarnet is nephrotoxic and causes electrolyte disturbance.
• Oseltamivir: oral prodrug, renally cleared.
• Antiretrovirals: grouped by target; always combined.
• Hepatitis B and C antivirals: used to suppress or cure chronic infection.

Resistance. Occurs rapidly with monotherapy in HIV, hepatitis B and influenza under pressure, and with thymidine kinase mutations in herpesviruses in immunocompromised patients.

Herpesvirus (adult, representative).

• Herpes simplex encephalitis: aciclovir 10 mg/kg intravenously every 8 hours for 14 to 21 days.
• Genital herpes first episode: aciclovir 400 mg three times daily, or valaciclovir 500 mg to 1 g twice daily, for 7 to 10 days.
• Herpes zoster: valaciclovir 1 g three times daily for 7 days, started within 72 hours of the rash.

Influenza. Oseltamivir 75 mg twice daily for 5 days, started within 48 hours for outpatients at risk, and in all hospitalised patients regardless of duration.

HIV and hepatitis B. Treatment is lifelong in most settings and requires combination regimens.

Timing. Benefit falls with delay for most antivirals, particularly herpesviruses and influenza, so treatment starts on clinical suspicion.

Region. In East Africa, HIV, hepatitis B and herpesviruses account for most antiviral use. Ebola (Zaire ebolavirus) has specific monoclonal antibody treatment given in designated treatment centres, while care of Marburg disease is largely supportive.

Class safety.

• Aciclovir: crystal nephropathy with rapid infusion or poor hydration; neurotoxicity in renal failure.
• Ganciclovir and valganciclovir: neutropenia, anaemia, thrombocytopenia; teratogenic.
• Foscarnet: nephrotoxicity, hypocalcaemia, hypomagnesaemia, seizures.
• Tenofovir disoproxil: renal tubular injury, bone loss; entecavir: lactic acidosis in advanced liver disease.
• Oseltamivir: nausea; rare neuropsychiatric events.

Monitoring. Creatinine, full blood count and liver enzymes before and during therapy; electrolytes with foscarnet; hydration with aciclovir.

Special groups.

• Pregnancy: aciclovir and oseltamivir are used when indicated; tenofovir is used in hepatitis B and HIV; ganciclovir is avoided unless essential.
• Breastfeeding: aciclovir and valaciclovir are compatible.
• Kidney impairment: adjust the dose or interval to creatinine clearance for aciclovir, valaciclovir, valganciclovir, oseltamivir, foscarnet and tenofovir.
• Children and older adults: use weight-based dosing and monitor renal function.

Referral and escalation. Refer for encephalitis, immunocompromise, cytomegalovirus disease, antiviral resistance and chronic hepatitis.