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Pathophysiology
Clinical meaning
Antiviral agents target specific stages of the viral replication cycle. Unlike bacteria, viruses are obligate intracellular parasites that hijack host cell machinery. The viral life cycle includes attachment (binding to host cell receptors), penetration (entry via fusion or endocytosis), uncoating (release of viral genome), replication (genome copying using viral or host polymerases), assembly (packaging new virions), and release (budding or cell lysis). Antiviral drugs exploit differences between viral and host processes: nucleoside/nucleotide analogs (acyclovir, tenofovir, sofosbuvir) mimic natural nucleotides and incorporate into growing viral DNA/RNA chains causing premature termination; protease inhibitors (ritonavir, simeprevir) block viral polyprotein cleavage essential for producing functional viral proteins; neuraminidase inhibitors (oseltamivir) prevent influenza virion release from host cells; integrase inhibitors (dolutegravir) block HIV proviral DNA integration into the host genome. Resistance develops through mutations in viral enzymes that reduce drug binding affinity, making combination therapy and appropriate prescribing critical.
Diagnostics & workup:
- Viral-specific PCR (quantitative): gold standard for HSV, CMV, HIV, HCV, influenza; provides viral load for treatment monitoring
- Serologic testing: IgM (acute infection) vs IgG (prior exposure/immunity); paired acute and convalescent titers confirm seroconversion
- Rapid antigen testing: influenza A/B rapid tests (lower sensitivity than PCR), rapid HIV 4th-gen Ag/Ab combination assay
- Hepatitis panel: HBsAg, anti-HBs, anti-HBc IgM/IgG, HCV antibody with reflex RNA confirmation
- HIV testing: 4th-generation combination Ag/Ab test, confirmatory HIV-1/HIV-2 differentiation assay, viral load (copies/mL), CD4 count
- Genotypic resistance testing: performed before initiating antiretroviral therapy for HIV or when treatment failure occurs to guide regimen selection
Risk factors:
- Immunocompromised states: HIV/AIDS, organ transplant recipients, chemotherapy, chronic corticosteroid use
- Extremes of age: neonates with immature immune systems and elderly with immunosenescence
- Chronic comorbidities: diabetes, CKD, COPD, liver disease increasing susceptibility and severity
- Healthcare workers and close contacts with high exposure risk
- Lack of vaccination or incomplete immunization series
- Travel to endemic areas (dengue, Zika, Japanese encephalitis)
- Injection drug use or high-risk sexual behavior (HIV, hepatitis B/C)
- Pregnancy: altered immune response and specific fetal risks from certain viral infections
Management
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Prescribing & monitoring
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Takeaways
Additional clinical detail, exam hooks, and takeaways continue in the full lesson.
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