Virology — HIV, Hepatitis & Herpesviruses
🟢 Lite — Quick Review (1h–1d)
Rapid summary for last-minute revision before your exam.
HIV: Retrovirus (RNA); CD4+ T-cell count = disease progression marker. CD4 <200 = AIDS-defining illnesses.
Hepatitis key distinctions:
- HAV: Fecal-oral, acute, self-limiting, no chronicity, IgM anti-HAV = acute infection
- HBV: Blood/sexual, chronicity (10% adults), Hep B sAg (HBsAg) = infection; anti-HBs = immunity; HBcAb (anti-HBc) = exposure
- HCV: Blood-borne, chronicity (80%), leading cause of cirrhosis and liver cancer; anti-HCV = screening; HCV RNA = active infection
- Hepatitis B serology: HBsAg+ HBeAg+ anti-HBc IgM = acute/replicative phase; HBsAg- anti-HBs+ anti-HBc+ = recovered/immune
Herpesviruses (HHV 1–8): HSV-1 (oral), HSV-2 (genital), VZV (chickenpox/shingles), EBV (infectious mononucleosis), CMV (CMV retinitis in AIDS, congenital), HHV-6 (roseola), HHV-8 (Kaposi sarcoma)
⚡ Exam tip: HIV question → always check CD4 count and decide on OI prophylaxis. HBV question → read window period carefully.
🟡 Standard — Regular Study (2d–2mo)
Standard content for students with a few days to months.
HIV / AIDS
Structure
- Family: Retroviridae; genus Lentivirus
- Genome: Two copies of +sense ssRNA; reverse transcriptase, integrase, protease
- Envelope: gp120 (binds CD4 + coreceptor CCR5/CXCR4) and gp41 (fusion)
- Target: CD4+ T helper cells (also macrophages, dendritic cells, microglia)
Transmission
Blood, sexual contact (receptive anal > receptive vaginal > insertive), perinatal (vertical), breastfeeding, needlestick (0.3% risk per exposure)
Clinical Stages
| Stage | CD4 Count | Features |
|---|---|---|
| Acute HIV infection | Normal or ↓ | Mononucleosis-like syndrome (fever, rash, lymphadenopathy, pharyngitis) 2–4 weeks after exposure |
| Chronic HIV infection (clinical latency) | 200–500 | Asymptomatic or persistent generalized lymphadenopathy |
| AIDS | <200 cells/µL | OIs, malignancies, wasting |
AIDS-defining illnesses: PCP pneumonia, toxoplasmosis, Cryptococcal meningitis, disseminated MAC, esophageal candidiasis, CMV retinitis, Kaposi sarcoma, NHL, invasive cervical cancer, HIV encephalopathy, recurrent pneumonia, chronic cryptosporidiosis.
Opportunistic Infections by CD4 Count
| CD4 Count | Infection |
|---|---|
| <200 | PCP pneumonia, esophageal candidiasis, Kaposi sarcoma |
| <100 | Toxoplasma encephalitis, Cryptococcal meningitis |
| <50 | CMV retinitis, disseminated MAC, CNS lymphoma |
Diagnosis
- Screening: ELISA / CMIA (detects anti-HIV-1/2); window period 3–12 weeks
- Confirmatory: Western blot (anti-HIV-1/2) or rapid point-of-care tests
- Acute infection: HIV RNA PCR (viral load) — detectable within 7–14 days (before antibodies)
- Monitoring: CD4 count (every 3–6 months), viral load (every 3–6 months)
HIV-1 vs HIV-2
- HIV-1 is globally predominant; HIV-2 is West Africa (lower transmissibility, slower progression)
- HIV-2 is inherently resistant to NNRTIs (efavirenz, nevirapine)
Treatment (HAART / cART)
Classes:
- NRTIs (nucleoside reverse transcriptase inhibitors): Tenofovir (TDF/TAF), Emtricitabine, Zidovudine, Lamivudine
- NNRTIs (non-nucleoside): Efavirenz, Nevirapine, Rilpivirine
- Integrase inhibitors: Raltegravir, Dolutegravir, Bictegravir
- Protease inhibitors: Atazanavir, Darunavir (ritonavir or cobicistat-boosted)
- Entry inhibitors: Maraviroc (CCR5 antagonist), Enfuvirtide (fusion inhibitor)
Standard first-line: 2 NRTIs + 1 INSTI (e.g., TDF + FTC + Dolutegravir or Bictegravir/emtricitabine/TAF = Biktarvy)
Post-exposure prophylaxis (PEP): Start within 72 hours; continue for 28 days; 3-drug regimen (same as treatment)
PMTCT (prevention of mother-to-child transmission): Maternal HAART + neonatal zidovudine + avoid breastfeeding
Hepatitis Viruses
Comparative Overview
| Virus | Transmission | Incubation | Chronicity | Vaccine |
|---|---|---|---|---|
| HAV | Fecal-oral | 2–6 weeks | No (always self-limiting) | Yes (HepA) |
| HBV | Blood, sexual, perinatal | 6 weeks–6 months | 10% adults | Yes (HepB) |
| HCV | Blood | 6–12 weeks | 80% | No |
| HEV | Fecal-oral | 2–8 weeks | Rare (pregnant women at risk) | No |
Hepatitis B — Serology
| Marker | Significance |
|---|---|
| HBsAg | Active infection (acute or chronic); first marker to appear |
| Anti-HBs (HBsAb) | Immunity (natural recovery or post-vaccine) |
| Anti-HBc (HBcAb) | Exposure to HBV (does NOT indicate immunity) |
| HBeAg | Active viral replication; high infectivity |
| Anti-HBe (HBeAb) | Low infectivity; disease resolution |
| HBV DNA | Active replication; quantitative |
Window period: HBsAg has cleared but anti-HBs hasn’t appeared; only HBcAb IgM/IgG is positive → this period has highest infectivity
HBV and Liver Cancer
- HBV is a direct oncogenic virus (like HPV for cervical cancer)
- Chronic HBV → cirrhosis → hepatocellular carcinoma (HCC)
- HBV X protein (HBx) is oncogenic
- HCC surveillance: 6-monthly AFP + liver ultrasound in cirrhotics and chronic HBV carriers
Hepatitis C
- Leading cause of liver transplantation in the US
- Leading cause of chronic liver disease, cirrhosis, and HCC worldwide
- Genotypes 1 (most common globally), 2, 3; genotype determines treatment duration
- Treatment: Direct-acting antivirals (DAAs) — Sofosbuvir/Ledipasvir, Elbasvir/Grazoprevir, Glecaprevir/Pibrentasvir; cure rates >95%
Herpesviruses
HSV-1 and HSV-2
- Family: Herpesviridae (HHV-1 and HHV-2); large dsDNA virus
- Transmission: HSV-1 — oral contact (kissing, shared utensils); HSV-2 — sexual contact
- Primary infection: Often asymptomatic; can cause gingivostomatitis (HSV-1) or genital herpes (HSV-2)
- Latency: Neuronal ganglia (HSV-1 → trigeminal ganglion; HSV-2 → sacral ganglia)
- Reactivation: Fever, stress, immunosuppression → cold sores (HSV-1) or genital ulcers (HSV-2)
- Diagnosis: Tzanck smear (multinucleated giant cells), PCR, viral culture
- Treatment: Acyclovir, Valacyclovir, Famciclovir (DNA polymerase inhibitors)
Varicella-Zoster Virus (VZV, HHV-3)
- Primary infection: Chickenpox (varicella) — vesicular rash “dew drops on rose petal,” centripetal distribution, crops at different stages
- Complications: Pneumonia (adults), encephalitis, cerebellar ataxia, neonatal varicella (if mother infected 5 days before to 2 days after delivery)
- Reactivation: Herpes zoster (shingles) — dermatomal, vesicular rash; most common in thoracic dermatomes; postherpetic neuralgia (persistent pain after rash heals) is major complication
- Vaccine: Varicella vaccine (live attenuated) for children; shingles vaccine (RZV/Shingrix) for adults >50 years (recombinant, not live)
Epstein-Barr Virus (EBV, HHV-4)
- Infectious mononucleosis: “Kissing disease”; fever, pharyngitis (exudative tonsillitis), posterior cervical and axillary lymphadenopathy, splenomegaly, fatigue
- Hallmark: Atypical lymphocytosis (Downey cells = CD8+ T cells); heterophile antibodies (Monospot test) — positive in 85% of adolescents/adults
- EBV associations: Burkitt lymphoma (African jaw, associated with EBV + malaria co-infection), nasopharyngeal carcinoma (China/Southeast Asia), Hodgkin lymphoma (some cases), post-transplant lymphoproliferative disorder, oral hairy leukoplakia (HIV/AIDS)
- Diagnosis: Heterophile antibody test (Monospot), anti-VCA IgM/IgG, EBNA IgG
Cytomegalovirus (CMV, HHV-5)
- Prevalence: 50–80% adults seropositive
- Congenital CMV: #1 non-genetic cause of sensorineural hearing loss; petechial rash (“blueberry muffin”), periventricular calcifications, microcephaly, hepatosplenomegaly
- CMV in immunocompromised: Retinitis (most common in AIDS, CD4 <50; “pizza pie” or “cottage cheese and ketchup” fundoscopic appearance), colitis, pneumonitis
- Infectious mononucleosis-like syndrome in immunocompetent individuals
- Diagnosis: Shell vial culture (early antigen), PCR, CMV antigenemia; heterophile-negative mononucleosis
- Treatment: Ganciclovir (first-line for CMV retinitis), Valganciclovir (oral prodrug)
🔴 Extended — Deep Study (3mo+)
Comprehensive coverage for students on a longer study timeline.
HIV — OI Prophylaxis Thresholds
| OI | Prophylaxis Trigger | Drug |
|---|---|---|
| PCP pneumonia | CD4 <200 or oropharyngeal candidiasis | TMP-SMX |
| Toxoplasmosis | CD4 <100 + positive Toxoplasma IgG | TMP-SMX |
| Disseminated MAC | CD4 <50 | Azithromycin |
| Cryptococcal meningitis | Not routinely recommended; treat when diagnosed | Amphotericin B + Flucytosine |
| TB | Positive IGRA or exposure | Isoniazid + pyridoxine |
Immune Reconstitution Inflammatory Syndrome (IRIS)
- Occurs within weeks–months of starting HAART
- Paradoxical worsening of OI symptoms as immune system recovers
- More common when starting HAART at very low CD4 counts
- Treatment: Continue HAART; short course of corticosteroids for severe cases
- Common unmasking IRIS: CMV retinitis, TB, MAC, PML
Prion Diseases (NEET PG Note)
Not viral but often asked together: Prion diseases are rapidly progressive dementias with spongiform pathology. Creutzfeldt-Jakob disease (CJD) is the most common. Kuru in Fore tribe of Papua New Guinea (ritual cannibalism). Rapidly progressive dementia with startle myoclonus, ataxia. EEG: periodic sharp wave complexes. 4-1-4-1 pattern. No known treatment.
Key NEET PG Pearls
- HIV: CD4 <200 = PCP prophylaxis (TMP-SMX); CD4 <100 = Toxoplasma prophylaxis; CD4 <50 = MAC prophylaxis (azithromycin)
- AIDS malignancies: Kaposi sarcoma (HHV-8), NHL (EBV), cervical cancer (HPV)
- Oral hairy leukoplakia on lateral tongue = EBV in HIV (not candidiasis, doesn’t scrape off)
- Hepatitis B: HBsAg positive = infection; anti-HBs positive = immunity; anti-HBc alone = window period or occult infection
- Hepatitis C is the leading cause of chronic liver disease, cirrhosis, and HCC; treat with DAAs
- Hepatitis A: IgM anti-HAV = acute infection; IgG anti-HAV = past infection or vaccine; never becomes chronic
- EBV infectious mononucleosis: Fever + exudative tonsillitis + posterior lymphadenopathy + splenomegaly + atypical lymphocytes; Monospot positive
- VZV reactivation (shingles): vesicular rash in dermatomal distribution; treat within 72 hours with valacyclovir
- Congenital CMV: Most common congenital infection; sensorineural hearing loss is most common sequela
- CMV retinitis in AIDS: “pizza pie” or “cottage cheese and ketchup” appearance; treat with ganciclovir/valganciclovir
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