Antiviral Chemotherapy, Excluding Antiretroviral Drugs¶
Chapter 196 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Antiviral drugs target specific viral enzymes (e.g., DNA polymerase, reverse transcriptase) to inhibit replication.
- Herpesvirus treatments include acyclovir, valacyclovir, famciclovir, ganciclovir, and foscarnet with dosing adjusted for renal function.
- Respiratory viruses (influenza, RSV) are treated with neuraminidase inhibitors (oseltamivir, zanamivir), ribavirin, and newer DAAs (nirmatrelvir, remdesivir).
- Hepatitis B and C are managed with nucleos(t)ide analogues (tenofovir, entecavir) and direct-acting antivirals (DAAs) with high SVR rates (>95%).
- Resistance monitoring and drug interactions are critical for optimizing antiviral therapy.
1. DEFINITION & OVERVIEW¶
Antiviral chemotherapy targets viral replication mechanisms. Viruses replicate in host cells, requiring drugs to inhibit specific viral enzymes or processes (e.g., DNA/RNA polymerase, protease, entry). Antivirals are used for treatment, prevention, and management of viral infections, with dosing adjusted for renal function and resistance monitoring.
1.1 Virus-Specific Antibodies¶
Antibody tests (ELISA, Western blot) detect prior viral infection or vaccination. HIV testing uses ELISA followed by Western blot for confirmation. Hemagglutination inhibition assays assess surface protein-specific antibodies.
1.2 Immunization¶
Vaccines use inactivated viruses (e.g., polio), live attenuated viruses (e.g., MMR), or recombinant vectors (e.g., mRNA, adenovirus). Vaccines prevent viral disease and reduce transmission.
2. EPIDEMIOLOGY¶
Viral infections vary by type: herpesviruses (HSV, VZV, CMV) affect immunocompromised populations; influenza and RSV are seasonal; hepatitis B/C are global public health concerns. Resistance patterns differ between DNA/RNA viruses (e.g., HIV vs. HSV).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Viruses replicate using host machinery, with antivirals targeting specific steps (e.g., DNA polymerase for herpesviruses, protease for HIV). Resistance arises from viral mutations (e.g., CMV UL97 kinase, HSV thymidine kinase).
4. CLINICAL FEATURES¶
Herpesvirus infections (HSV, VZV, CMV) present with skin lesions, encephalitis, or retinitis. Influenza causes respiratory symptoms; RSV affects infants. Hepatitis B/C lead to liver inflammation, fibrosis, or cirrhosis. Resistance to antivirals may cause treatment failure.
5. DIFFERENTIAL DIAGNOSIS¶
Distinguish viral infections from bacterial/bacterial mimics (e.g., bacterial pneumonia vs. viral pneumonia). Consider co-infections (e.g., HIV/CMV) and non-infectious causes (e.g., autoimmune hepatitis).
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic tests include PCR for viral DNA/RNA, serology (antibody tests), and imaging (e.g., CT for pneumonia). Viral load monitoring guides treatment response. Resistance testing (e.g., CMV UL97 mutations) is critical for refractory cases.
7. MANAGEMENT & TREATMENT¶
Treatment varies by virus: herpesviruses use nucleosides (acyclovir, ganciclovir), respiratory viruses use neuraminidase inhibitors (oseltamivir), and hepatitis uses DAAs (sofosbuvir, glecaprevir/pibrentasvir). Resistance management includes drug rotation and combination therapy.
Table 196-1: Antiviral Drugs for Herpesvirus Treatment and Prophylaxis in Adults¶
| DISEASE | DRUG | ROUTE | ADULT DOSE | COMMENTS |
|---|---|---|---|---|
| Orolabial herpes, primary episode | Acyclovir | Oral | 400 mg tid × 7–10 d | Reduces duration of fever, lesions, and virus shedding |
| Orolabial herpes, primary episode | Valacyclovir | Oral | 1 g bid × 7–10 d | |
| Orolabial herpes, primary episode | Famciclovir | Oral | 500 mg bid or 250 mg tid × 7–10 d | |
| Orolabial herpes, recurrence | Acyclovir | Oral | 400 mg 5 times daily × 5 d | Reduces duration of lesions by 1–2 d if given during prodrome |
| Orolabial herpes, recurrence | Valacyclovir | Oral | 2 g bid × 1 d | |
| Orolabial herpes, recurrence | Famciclovir | Oral | 1500 mg × 1 d | |
| Orolabial herpes, suppression | Acyclovir | Oral | 400 mg bid | In patients with >6 recurrences per year, reduces number of recurrences by ~50% |
| DISEASE | DRUG | ROUTE | ADULT DOSE | COMMENTS |
|---|---|---|---|---|
| Orolabial herpes, suppression | Valacyclovir | Oral | 500 mg or 1 g once daily | |
| Orolabial herpes, suppression | Famciclovir | Oral | 500 mg bid | |
| Genital herpes, primary episode | Acyclovir | Oral | 400 mg tid or 200 mg 5 times daily × 7–10 d | Reduces duration of symptoms, genital lesions, and virus shedding |
| Genital herpes, primary episode | Valacyclovir | Oral | 1 g bid × 7–10 d | |
| Genital herpes, primary episode | Famciclovir | Oral | 250 mg tid × 7–10 d | |
| Genital herpes, recurrence | Acyclovir | Oral | 800 mg tid × 2 d or 400 mg tid × 5 d | Reduces duration of symptoms, genital lesions, and virus shedding by 1–2 d |
| Genital herpes, recurrence | Valacyclovir | Oral | 500 mg bid × 3 d or 1 g daily × 5 d | |
| Genital herpes, recurrence | Famciclovir | Oral | 500 mg once, then 250 mg bid × 2 d | |
| Genital herpes, suppression | Acyclovir | Oral | 400 mg bid | Reduces recurrence rates from 80–85% to 25–30% |
| Genital herpes, suppression | Valacyclovir | Oral | 250 mg bid | |
| Genital herpes, suppression | Famciclovir | Oral | 500 mg to 1 g daily | |
| HSV encephalitis | Acyclovir | IV | 10–15 mg/kg q8h × 14–21 d | Reduces mortality and sequelae |
| HSV keratitis | Acyclovir | Topical | 3% ophthalmic ointment, 5 times daily | Shortens duration of disease |
| HSV keratitis | Trifluridine | Topical | 1% ophthalmic solution, 1 drop q2h when awake | Tolerated better with prolonged treatment |
| Mucocutaneous herpes in immunoco mpromised patients | Acyclovir | IV | 5 mg/kg q8h × 7–14 d | IV acyclovir reduces time to healing, duration of pain, and virus shedding |
| Mucocutaneous herpes in immunoco mpromised patients | Valacyclovir | Oral | 500 mg to 1 g bid × 7–10 d | |
| Mucocutaneous herpes in immunoco mpromised patients | Famciclovir | Oral | 500 mg bid × 7–10 d | |
| Varicella | Acyclovir | Oral | 20 mg/kg (800 mg max) 5 times daily × 5 d | Has modest effect on symptoms, reduces fever duration by 1 day |
| DISEASE | DRUG | ROUTE | ADULT DOSE | COMMENTS |
|---|---|---|---|---|
| Varicella | Valacyclovir | Oral | 20 mg/kg (1 g max) tid × 5 d | |
| Zoster | Acyclovir | Oral | 800 mg 5 times daily × 7 d | Reduces time for last new lesion formation, virus shedding, and pain duration |
| Zoster | Valacyclovir | Oral | 1 g tid × 7 d | |
| Zoster | Famciclovir | Oral | 500 mg tid × 7 d | |
| Varicella or zoster, disseminated | Acyclovir | IV | 10 mg/kg q8h × 7 d | Reduces cutaneous dissemination |
| Cytomegalovirus disease | Ganciclovir | IV | 5 mg/kg q12h × 14–21 d, then 5 mg/kg daily | Neutropenia and thrombocytopenia common after 1 week |
| Cytomegalovirus disease | Valganciclovir | Oral | 900 mg bid × 14–21 d, then 90 mg daily | Levels and side effects similar to ganciclovir |
| Cytomegalovirus disease | Foscarnet | IV | 60 mg/kg q8h × 14–21 d, then 90–120 mg daily | Nephrotoxicity, electrolyte abnormalities; give with additional saline |
| Cytomegalovirus disease | Cidofovir | IV | 5 mg/kg once weekly twice, then every other week | Nephrotoxicity; give with probenecid and saline |
| Cytomegalovirus disease | Maribavir | Oral | 400 mg bid | Used for disease refractory to ganciclovir, foscarnet, or cidofovir |
| Cytomegalovirus disease | Letermovir | Oral | 480 mg qd | Recommended for prophylaxis in transplant recipients |
Table 196-2: Antiviral Drugs for Respiratory Virus Treatment and Prophylaxis in Adults¶
| DISEASE | DRUG | ROUTE | ADULT DOSE | COMMENTS |
|---|---|---|---|---|
| Influenza A, B | Oseltamivir | Oral | 75 mg bid × 5 d | Shortens duration of symptoms by 1 d when given within 2 d of onset |
| Influenza A, B | Zanamivir | Inhaled | 10 mg bid × 5 d | Shortens duration of symptoms by 1–2 d when given within 2 d of onset |
| Influenza A, B | Peramivir | IV | 600 mg once | Shortens duration of symptoms by 1–2 d when given within 2 d of onset |
| Influenza A, B | Baloxavir | Oral | 40 mg once; if >80 kg, 80 mg once | Active against influenza A and B, including avian strains |
| DISEASE | DRUG | ROUTE | ADULT DOSE | COMMENTS |
|---|---|---|---|---|
| Influenza A | Amantadine | Oral | 100 mg bid × 5 d | Most influenza virus strains are resistant |
| Influenza A | Rimantadine | Oral | 100 mg bid × 5 d | Most influenza virus strains are resistant |
| Respiratory syncytial virus | Ribavirin | Inhaled | Aerosol from reservoir containing 20 mg/mL for 12–18 h/d × 3–7 d | Reduces severity of symptoms in hospitalized infants |
| SARS-CoV-2 | Nirmatrelvir/ritonavir | Oral | 300 mg/100 mg bid × 5 days | Reduces rate of hospitalization by 50% within 30 days after diagnosis |
| SARS-CoV-2 | Remdesivir | IV | 200 mg on day 1, then 100 mg qd × 2 d for outpatients, × 4 days for inpatients | Reduces duration of hospitalization in some studies |
| SARS-CoV-2 | Molnupiravir | Oral | 800 mg q12h × 5 days | Recommended for patients when nirmatrelvir or remdesivir are not available |
7.1 Herpesvirus Therapy¶
Acyclovir (oral/intravenous) is first-line for HSV/VZV; ganciclovir for CMV. Resistance management includes valacyclovir, famciclovir, and foscarnet. Renal dosing adjustments are required.
7.2 Respiratory Viruses¶
Neuraminidase inhibitors (oseltamivir, zanamivir) for influenza; ribavirin for RSV. DAAs (nirmatrelvir, remdesivir) for SARS-CoV-2. Prophylaxis in high-risk patients (e.g., transplant recipients).
7.3 Hepatitis B/C¶
Nucleos(t)ide analogues (tenofovir, entecavir) for HBV; DAAs (sofosbuvir, glecaprevir/pibrentasvir) for HCV. Monitoring includes viral load, liver function, and resistance testing.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis varies by virus: herpesviruses may recur in immunocompromised patients; influenza can lead to severe complications (e.g., ARDS); hepatitis B/C may progress to cirrhosis or hepatocellular carcinoma. Antiviral resistance and treatment failure are significant complications.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid acyclovir in the first trimester; use valacyclovir for HSV. Pediatric dosing adjusted for weight. Renal impairment requires dose reductions for all antivirals. Drug interactions (e.g., CYP3A inhibitors/inducers) affect efficacy and toxicity.
10. KEY POINTS & CLINICAL PEARLS¶
- Antiviral resistance is common in RNA viruses (e.g., HSV, HIV) due to high mutation rates. 2. Renal dosing adjustments are critical for all antivirals. 3. DAAs achieve >95% SVR for HCV genotypes 1–6. 4. Prophylaxis with valacyclovir reduces HSV transmission. 5. Monitor for drug interactions (e.g., CYP3A inhibitors).