Key Facts

Antiviral drugs target specific stages of viral replication. Unlike bacteria, viruses rely on host cell machinery, making selective toxicity more challenging. Advances in antiviral therapy have transformed outcomes for HIV, hepatitis C, and herpes virus infections.

Classification by Target

• Nucleoside/nucleotide analogues: aciclovir, valaciclovir, ganciclovir, tenofovir, lamivudine — incorporate into viral DNA → chain termination
• Neuraminidase inhibitors: oseltamivir, zanamivir — prevent influenza virion release
• Protease inhibitors: ritonavir, atazanavir — inhibit viral polyprotein processing (HIV)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs): efavirenz, rilpivirine — allosteric inhibition of HIV RT
• Integrase strand transfer inhibitors (INSTIs): dolutegravir, bictegravir — prevent HIV DNA integration; preferred first-line
• NS5A/NS5B inhibitors: ledipasvir, sofosbuvir, velpatasvir — direct-acting antivirals for HCV
• Monoclonal antibodies: palivizumab (RSV prophylaxis in high-risk infants)

Pathophysiology

• Viruses replicate using host cell machinery → difficult to target without harming host
• Nucleoside analogues: require viral enzyme activation (e.g. aciclovir activated by viral thymidine kinase) → selective toxicity
• HIV: integrates into host genome → lifelong infection; ART suppresses but does not cure
• HCV: does not integrate → cure possible with DAAs

Indications by Drug

Herpes Viruses:

• Aciclovir 200 mg 5 times daily for 5 days: primary genital herpes
• Aciclovir 800 mg 5 times daily for 7 days: herpes zoster (shingles)
• Valaciclovir 1 g TDS for 7 days: herpes zoster (preferred — simpler dosing)
• IV aciclovir 10 mg/kg TDS: herpes encephalitis, severe VZV in immunocompromised
• Aciclovir 400 mg BD: suppressive therapy for recurrent genital herpes (≥6 episodes/year)
• Ganciclovir/valganciclovir: CMV retinitis, CMV disease in transplant recipients

Influenza:

• Oseltamivir 75 mg BD for 5 days: treatment (within 48 hours of symptom onset)
• Oseltamivir 75 mg OD for 10 days: post-exposure prophylaxis
• Zanamivir 10 mg (2 inhalations) BD: alternative; inhaled

HIV:

• First-line ART (BHIVA/NICE NG206): 2 NRTIs + INSTI (e.g. emtricitabine/tenofovir alafenamide + dolutegravir)
• PrEP: emtricitabine/tenofovir disoproxil OD — prevents HIV acquisition
• PEP: within 72 hours; 4-week ART course

Hepatitis B:

• Tenofovir or entecavir: long-term suppressive therapy (not curative)

Hepatitis C:

• Sofosbuvir/velpatasvir 8–12 weeks: pan-genotypic; cure rate >95%

Red Flags

• IV aciclovir: crystalline nephropathy → ensure adequate hydration (2–3 L/day)
• Ganciclovir: bone marrow suppression (neutropenia) → monitor FBC
• Oseltamivir: resistance in immunocompromised — consider zanamivir
• ART drug interactions: ritonavir is a potent CYP3A4 inhibitor — check all co-medications

Before Starting

• Viral confirmation: PCR (HSV, VZV, CMV, HIV, HCV, HBV)
• U&Es: renal function — dose adjustment for aciclovir, ganciclovir, tenofovir
• LFTs: hepatitis B/C treatment monitoring
• FBC: ganciclovir (bone marrow suppression)
• HIV: viral load, CD4 count, genotypic resistance testing before starting ART
• HCV: genotype, viral load, FibroScan/liver assessment before DAA therapy

Monitoring

• HIV: viral load at 4–8 weeks after starting ART → aim undetectable (<200 copies/mL); CD4 count; renal function (tenofovir)
• HCV: viral load at end of treatment and 12 weeks post-treatment (SVR12 = cure)
• Renal function: IV aciclovir, tenofovir, ganciclovir
• FBC: ganciclovir, valganciclovir, zidovudine

Special Tests

• Genotypic resistance testing: HIV (before starting ART and if treatment failure), HBV, HCV
• HLA-B*5701 testing: mandatory before abacavir (hypersensitivity)

Herpes Virus Infections

• Oral aciclovir/valaciclovir: for HSV, VZV — start within 72 hours of rash onset
• IV aciclovir 10 mg/kg TDS: HSV encephalitis (14–21 days), severe VZV, immunocompromised
• Adequate hydration: essential for IV aciclovir (prevent crystalline nephropathy)

Influenza

• Oseltamivir 75 mg BD for 5 days: start within 48 hours; recommended for at-risk patients and during confirmed outbreaks
• Prophylaxis: oseltamivir 75 mg OD for 10 days for close contacts of confirmed cases

HIV

• Lifelong ART: start as soon as diagnosed (regardless of CD4 count — NICE NG206, START trial)
• First-line: 2 NRTIs (emtricitabine/TAF) + INSTI (dolutegravir)
• Adherence: critical — non-adherence leads to resistance
• U=U (Undetectable = Untransmittable): undetectable viral load means no sexual transmission

Hepatitis C

• Direct-acting antivirals (DAAs): pan-genotypic regimen (sofosbuvir/velpatasvir) 12 weeks
• Cure rate (SVR12): >95%
• Screen for HBV co-infection before starting (risk of HBV reactivation)

Hepatitis B

• Tenofovir or entecavir: long-term suppressive therapy
• Treatment indication: elevated ALT + high viral load + fibrosis
• Not curative — aim for HBV DNA suppression

Referral Criteria

• HIV clinic: all new diagnoses; specialist prescribing and monitoring
• Hepatology/gastroenterology: HCV/HBV treatment
• Infectious diseases: complex viral infections, treatment failure
• Ophthalmology: CMV retinitis

• HSV/VZV: excellent with early treatment; aciclovir reduces severity and duration
• HIV: near-normal life expectancy with early ART and adherence
• Hepatitis C: >95% cure with DAAs — WHO target of HCV elimination by 2030
• Hepatitis B: lifelong suppressive therapy; functional cure (HBsAg loss) rare
• Influenza: oseltamivir reduces illness duration by ~1 day and complications
• Drug resistance: major concern for HIV (non-adherence) and HSV (immunocompromised)

Antiviral Drug Summary

HIV Treatment Cascade (UK)