Step 1 · Microbiology

Hepatitis Viruses & HIV

Name: Hepatitis Viruses & HIV
Creator: Veli Bakalov, MD

Serology windows and the CD4 opportunistic-infection timeline

Microbiology·Virology·5 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Vowels hit your bowels: HAV and HEV are fecal-oral and acute only; HBV (DNA hepadnavirus), HCV (flavivirus), and HDV are bloodborne/sexual and can become chronic.
HEV is waterborne and causes fulminant hepatitis with ~20% mortality in pregnancy; HAV has no carrier state (IgM = active, IgG = immunity).
HBsAg = active infection; anti-HBs = immunity; anti-HBc IgM = acute; anti-HBc IgG = prior/chronic; HBeAg = high infectivity; vaccine produces anti-HBs only.
Window period: HBsAg and anti-HBs are both negative, and anti-HBc IgM is the only marker of infection.
HBV integrates into host DNA and can cause HCC without cirrhosis; HDV needs HBsAg, and superinfection on chronic HBV is severe or fulminant.
HCV becomes chronic in ~80% (cirrhosis, HCC); no vaccine because envelope proteins mutate rapidly; diagnose with antibody plus HCV RNA; cured by direct-acting antivirals.
HIV: gp120 binds CD4 plus CCR5 (early, macrophages) or CXCR4 (late, T cells); gp41 fuses; homozygous CCR5-Δ32 confers resistance.
Screen with a 4th-generation p24 antigen/antibody assay and confirm with an HIV-1/HIV-2 differentiation assay; viral load tracks treatment response.
CD4 <200: PCP (TMP-SMX) and AIDS; <100: Toxoplasma, Cryptococcus, Candida esophagitis; <50: CMV retinitis, MAC; -navir = protease inhibitor, -tegravir = integrase inhibitor.

Hepatitis viruses: two routes, five viruses

Vowels hit your bowels. Hepatitis A and E spread fecal-orally and cause only acute disease. Hepatitis B (a DNA hepadnavirus), C (a flavivirus), and D (a defective RNA virus) spread parenterally or sexually and can become chronic.

The hepatitis viruses

Virus	Family (genome)	Transmission	Chronicity and clues
HAV	Picornavirus (RNA)	Fecal-oral: shellfish, travel	Acute, self-limited; no carrier state; vaccine
HBV	Hepadnavirus (partially dsDNA, reverse transcriptase)	Parenteral, sexual, perinatal	Can be chronic; HCC even without cirrhosis
HCV	Flavivirus (RNA)	Mainly parenteral (injection drug use)	Chronic in ~80%; no vaccine
HDV	Defective RNA virus	Parenteral; needs HBsAg	Superinfection on chronic HBV is severe
HEV	Hepevirus (RNA)	Waterborne, fecal-oral	Acute; ~20% mortality in pregnancy

HAV and HEV. HAV causes acute, self-limited hepatitis after contaminated shellfish or travel, with no carrier state. Anti-HAV IgM means active infection, and IgG means immunity (from infection or the vaccine). HEV is waterborne and also acute, but it can cause fulminant hepatitis with high mortality (~20%) in pregnant women.

~80%of HCV infections become chronic

~20%HEV mortality in pregnancy

Hepatitis B and D

HBV biology. HBV is a partially double-stranded DNA hepadnavirus that replicates through an RNA intermediate using reverse transcriptase. Its DNA integrates into host chromosomes, so it can drive hepatocellular carcinoma even without cirrhosis, unlike HCV. Risk of chronic infection is highest when acquired at birth (about 90% of infected newborns vs about 5% of infected adults), which is why exposed newborns receive vaccine plus hepatitis B immune globulin. Extrahepatic associations include polyarteritis nodosa and membranous nephropathy.

Reading the markers. HBsAg = active infection (acute or chronic). Anti-HBs = immunity (recovery or vaccine). Anti-HBc IgM = acute or recent infection; anti-HBc IgG = prior or chronic exposure. HBeAg = active replication and high infectivity; anti-HBe = low infectivity. Because the vaccine is recombinant HBsAg, vaccination produces anti-HBs alone, whereas natural infection also produces anti-HBc.

HBV serologic patterns

Scenario	HBsAg	Anti-HBs	Anti-HBc	HBeAg
Acute infection	+	−	IgM	+
Window period	−	−	IgM	−
Chronic infection	+	−	IgG	+ (high infectivity) or − (low)
Recovered	−	+	IgG	−
Vaccinated	−	+	−	−

The window period. In acute infection, markers appear in sequence: HBsAg and HBeAg first, then anti-HBc IgM, then anti-HBs with anti-HBc IgG on recovery. During the window, HBsAg has cleared but anti-HBs has not yet appeared, so anti-HBc IgM is the only marker of infection (anti-HBe may also be present). Recognizing this pattern prevents falsely calling the patient uninfected.

Hepatitis D. A defective virus that needs HBsAg as its envelope to enter cells. Coinfection (HBV and HDV acquired together) is usually self-limited; superinfection (HDV on top of chronic HBV) is severe and can be fulminant.

Hepatitis C

The chronic one. HCV becomes chronic in about 80% of infections and leads to cirrhosis and hepatocellular carcinoma. There is no vaccine: its RNA polymerase lacks proofreading, so the envelope glycoproteins mutate rapidly. Diagnose with anti-HCV antibody plus HCV RNA (RNA confirms active infection); direct-acting antivirals now cure it. Extrahepatic associations include mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda.

HIV: structure, entry, and diagnosis

Structure. HIV is a retrovirus with two copies of positive-sense RNA and three enzymes: reverse transcriptase, integrase, and protease. Genes: env (gp120 for attachment, gp41 for fusion), gag (p24 capsid), and pol (the enzymes). Protease cleaves the gag-pol polyprotein into mature enzymes, so protease inhibitors leave immature, noninfectious virions. The virus progressively depletes CD4 T cells.

gp120 binds CD4On helper T cells and macrophages
CoreceptorCCR5 on macrophages (early, M-tropic) or CXCR4 on T cells (late, T-tropic)
gp41 fusionViral and cell membranes merge
Reverse transcription and integrationProviral DNA enters the host genome; CD4 depletion follows

HIV cell entry

CCR5-Δ32. A homozygous 32-base-pair deletion in CCR5 confers resistance to infection; heterozygotes progress more slowly.

Diagnosis and monitoring. Screen with a 4th-generation antigen/antibody immunoassay, which detects p24 antigen as well as HIV antibody, then confirm with an HIV-1/HIV-2 antibody differentiation assay (which replaced the Western blot). Viral load (RNA PCR), not CD4 count, is the best measure of treatment response and transmission risk; the CD4 count gauges immune status and guides prophylaxis.

HIV: CD4 timeline, AIDS, and ART

Opportunistic infections as CD4 falls

CD4 (cells/mm³)	Typical infections	Prophylaxis / notes
<500	Oral thrush (Candida), hairy leukoplakia (EBV), Kaposi sarcoma (HHV-8), zoster	None specific
<200	Pneumocystis pneumonia	Start TMP-SMX; also the AIDS threshold
<100	Toxoplasma (ring-enhancing lesions), Cryptococcus, Candida esophagitis	TMP-SMX also prevents toxoplasmosis in seropositive patients
<50	CMV retinitis, MAC	Azithromycin for MAC when ART cannot be started promptly

Brain lesions in advanced HIV: ring-enhancing lesions suggest Toxoplasma (or primary CNS lymphoma), whereas PML from JC virus is non-enhancing white-matter disease.

Defining AIDS. A CD4 count below 200 cells/mm³, OR any AIDS-defining illness (such as PCP, esophageal candidiasis, Kaposi sarcoma, CMV retinitis, or CNS lymphoma) regardless of CD4 count.

<200CD4 count that defines AIDS and triggers PCP prophylaxis

Antiretroviral therapy. Combination ART is started in all patients. Drug classes map onto the viral life cycle:

Reverse transcriptase: NRTIs and NNRTIs.
Integrase: integrase inhibitors, ending in -tegravir.
Protease: protease inhibitors, ending in -navir.
Entry: enfuvirtide (blocks gp41 fusion) and maraviroc (blocks CCR5).

Suffix check: -navir = protease inhibitor; -tegravir = integrase inhibitor. Viral load, not CD4, tells you whether ART is working.