Viruses replicate inside host cells using host machinery, so selective targets are few. Antivirals block a step that is specific to the virus: entry, genome copying (polymerase or reverse transcriptase), integration, protein processing (protease), or release. Most antivirals suppress replication rather than eradicate the virus — latent herpesviruses, HIV, and hepatitis B persist. Hepatitis C is the exception: direct-acting antivirals cure it.

HIV principles

• Start ART for everyone with HIV as soon as possible, regardless of CD4 count
• Undetectable = untransmittable (U = U): a durably suppressed viral load prevents sexual transmission
• PrEP: daily oral tenofovir-based pills, injectable cabotegravir, or twice-yearly injectable lenacapavir; confirm a negative HIV test first and retest at the interval set for the product (about every 3 months for oral PrEP; at each injection for injectables)
• PEP: start as soon as possible and no later than 72 hours after exposure; continue for 28 days

Contraindications and cautions

• Abacavir: test for HLA-B*57:01 before starting — do not give if positive; never rechallenge after a suspected reaction
• Adjust doses of acyclovir, valacyclovir, ganciclovir, oseltamivir (creatinine clearance 60 mL/min or less), tenofovir, and entecavir for kidney function
• Zanamivir: not in asthma or COPD. Baloxavir: not in pregnancy
• Molnupiravir is not recommended in pregnancy (fetal toxicity in animals); use contraception during and for 4 days after treatment; male partners use contraception for 3 months after
• Ribavirin (still used in some HCV and RSV regimens) is teratogenic: two forms of contraception for the client and partners during treatment and for 6 months after; it also causes hemolytic anemia
• Valganciclovir: embryo-fetal toxicity — effective contraception during and after therapy

Pregnancy

• Oseltamivir is the preferred influenza antiviral
• ART is continued or started in pregnancy; dolutegravir-based regimens are preferred (early neural tube concerns were not confirmed). Acyclovir/valacyclovir suppression is offered from 36 weeks for recurrent genital herpes
• Breastfeeding with HIV: US guidance supports shared decision-making for people with sustained viral suppression (replacement feeding avoids all risk); WHO recommends breastfeeding with maternal ART and infant prophylaxis where safe replacement feeding is not assured — follow the national program

Interactions

• Ritonavir and cobicistat are strong CYP3A4 inhibitors ("boosters"). Nirmatrelvir–ritonavir and boosted protease inhibitors raise levels of some statins (simvastatin, lovastatin), amiodarone, tacrolimus, certain anticoagulants, sedatives (midazolam, triazolam), and ergots — a full medication review is required before prescribing
• Rifampin, St. John's wort, carbamazepine, and phenytoin lower many antiretroviral levels → treatment failure and resistance
• Integrase inhibitors chelate with polyvalent cations: take dolutegravir or bictegravir 2 hours before or 6 hours after antacids, laxatives, or supplements containing aluminum, magnesium, calcium, iron, or zinc (or together with food for calcium/iron with some products)
• Rilpivirine and atazanavir need stomach acid — proton pump inhibitors are contraindicated with rilpivirine
• Sofosbuvir + amiodarone → severe symptomatic bradycardia
• Nephrotoxic combinations (acyclovir or tenofovir with aminoglycosides, NSAIDs, or IV contrast) add kidney risk

1. Kidney protection with acyclovir: check baseline creatinine; hydrate well; infuse IV acyclovir over at least 1 hour (never IV push); monitor urine output and creatinine; watch for confusion in older adults
2. CBC with ganciclovir/valganciclovir and zidovudine; hold and report severe neutropenia or thrombocytopenia per protocol
3. Hazardous drug handling for ganciclovir and valganciclovir: gloves; do not crush or split tablets; pregnant staff follow institutional policy
4. HIV care: baseline HIV viral load, CD4, HLA-B*57:01 (if abacavir), hepatitis B serology (tenofovir, emtricitabine, and lamivudine also treat HBV — stopping them can cause a flare), kidney and liver tests, lipids, glucose, pregnancy test. Goal: viral load undetectable, usually within 3–6 months; monitor adherence at every contact
5. Hepatitis B/C: liver tests; HBV DNA; HCV RNA 12 weeks after therapy (sustained virologic response = cure); test for HBV before HCV DAAs
6. Influenza: start antivirals promptly — do not wait for test results in high-risk or hospitalized clients; droplet precautions
7. Screen every new drug (including over-the-counter and herbal products) against ritonavir/cobicistat-boosted regimens
8. Assess mental status with oseltamivir (children) and efavirenz; skin with abacavir and NNRTIs

• Antivirals do not cure herpes, HIV, or hepatitis B; they control the virus. Hepatitis C treatment is curative when finished
• Take ART every day at the same time; missing doses allows resistance. Keep a supply; do not stop without the provider
• Do not stop hepatitis B medicine on your own — the liver infection can flare dangerously
• Drink plenty of fluids with acyclovir or valacyclovir; start episodic herpes treatment at the first tingling (prodrome)
• Herpes can spread without visible sores; avoid contact with lesions and use condoms; suppressive therapy lowers transmission
• Oseltamivir: take with food; complete 5 days; report unusual behavior (children)
• Abacavir: carry the warning card; stop and call for fever, rash, GI or breathing symptoms — never restart after a reaction
• Tell every prescriber and pharmacist about HIV, COVID-19, or HCV medicines; avoid St. John's wort
• Separate integrase inhibitors from antacids, calcium, iron, and multivitamins
• Use effective contraception with ribavirin, molnupiravir, and valganciclovir

There are no specific antidotes for antiviral overdose; care is supportive.

• Acyclovir nephrotoxicity or neurotoxicity: stop or reduce the drug, hydrate; acyclovir is removed by hemodialysis
• Ganciclovir marrow suppression: hold the drug; growth factor (filgrastim) may be used
• Abacavir hypersensitivity: stop permanently; rechallenge can cause fatal hypotension
• Lactic acidosis (older NRTIs): fatigue, nausea, abdominal pain, rapid breathing — stop the drug; supportive care
• Interaction toxicity from ritonavir (e.g., statin rhabdomyolysis, oversedation, bradycardia) — identify and stop the affected drug
• HBV flare after stopping HBV-active drugs or during HCV DAA therapy — liver tests and restart HBV suppression

• Acyclovir/valacyclovir: HSV and VZV; hydrate, adjust for kidney function; IV acyclovir over 1 hour; zoster within 72 hours
• Oseltamivir: best within 48 hours, but give ASAP to hospitalized or high-risk clients regardless of timing; 75 mg twice daily × 5 days; preferred in pregnancy
• Zanamivir avoided in asthma/COPD; baloxavir avoided in pregnancy
• Nirmatrelvir–ritonavir: within 5 days; ritonavir = major CYP3A4 interactions
• Ganciclovir/valganciclovir: marrow suppression, hazardous handling
• Abacavir → HLA-B*57:01 test first; TDF → kidney and bone; efavirenz → vivid dreams
• ART for all with HIV, ASAP; U = U; PEP within 72 hours for 28 days
• Integrase inhibitors: separate from antacids, calcium, iron
• Stopping HBV drugs → hepatitis flare; HCV DAAs → HBV reactivation; sofosbuvir + amiodarone → bradycardia
• Ribavirin and molnupiravir: teratogenic — contraception