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Explain hiv

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HIV pathogenesis classification treatment overview 2025

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HIV - Human Immunodeficiency Virus

1. Overview

HIV (Human Immunodeficiency Virus) is a nontransforming human retrovirus belonging to the lentivirus family. It causes progressive destruction of cell-mediated immunity, ultimately leading to AIDS (Acquired Immunodeficiency Syndrome). There are two forms:

HIV-1: Most common worldwide; responsible for the global pandemic
HIV-2: Causes a similar but slower disease, predominantly in West Africa and India
Robbins & Kumar Basic Pathology, p. 199

2. Structure of HIV

HIV virion structure showing gp120, gp41, p17 matrix, p24 capsid, lipid bilayer, integrase, protease, RNA, and reverse transcriptase

The HIV virion is spherical with a cone-shaped electron-dense core, surrounded by a host cell-derived lipid envelope.

Component	Role
gp120	Binds CD4 receptor on target cells
gp41	Mediates membrane fusion
p17	Matrix protein beneath the envelope
p24	Major capsid protein; target of diagnostic assays
Reverse transcriptase	Converts viral RNA to proviral DNA
Integrase	Integrates proviral DNA into host genome
Protease	Cleaves precursor proteins for viral assembly

The genome contains three core genes: gag (nucleocapsid), pol (enzymes), and env (gp160 → gp120 + gp41), plus regulatory genes: tat, rev, vif, nef, vpr, vpu.

Robbins & Kumar Basic Pathology, p. 199

3. Transmission

Route	Notes
Sexual contact	Most common globally; unprotected anal intercourse carries highest risk
Parenteral (IV drug use)	Sharing contaminated needles
Blood/blood products	Largely eliminated by modern screening
Mother-to-child	During delivery, breastfeeding; ART in pregnancy dramatically reduces this

HIV is not transmitted by casual contact, saliva, tears, or insects.

4. Life Cycle and Pathogenesis

HIV life cycle - virus entry, replication, and release

Step-by-step:

Attachment: gp120 binds to CD4 receptor on T helper cells, macrophages, dendritic cells
Co-receptor binding: gp120 then binds to chemokine co-receptors (CCR5 or CXCR4), causing conformational change
Fusion: gp41 inserts fusion peptide into host cell membrane → viral genome enters cytoplasm
Reverse transcription: Viral RNA → double-stranded proviral DNA (via reverse transcriptase)
Integration: Proviral DNA integrates into host genome (via integrase) - can remain latent for years
Transcription & translation: Upon activation, proviral DNA is transcribed → viral proteins synthesized
Assembly & budding: New virions bud from host cell surface
Maturation: Protease cleaves precursor proteins → mature, infectious virion

Co-receptor tropism:

R5 strains (CCR5): Infect macrophages and T cells; predominate in early infection
X4 strains (CXCR4): T-tropic; appear in late disease, associated with rapid CD4 decline
~1% of Europeans with homozygous CCR5-Δ32 mutation are resistant to HIV infection
Robbins & Kumar Basic Pathology; Harrison's Principles of Internal Medicine 22E (2025)

5. CD4+ T Cell Depletion

The hallmark of HIV is progressive loss of CD4+ T cells through:

Direct mechanisms:

Loss of membrane integrity during viral budding
Syncytia formation (infected + uninfected cells fuse)
Accumulation of unintegrated viral DNA

Indirect mechanisms:

Apoptosis, pyroptosis (caspase-1 mediated)
Autoimmunity
Activation-induced cell death
Elimination of HIV-infected cells by immune responses

Normal CD4 count: ~500-1500 cells/μL. Disease progresses as CD4 falls.

Harrison's Principles of Internal Medicine 22E (2025)

6. Clinical Stages (CDC Classification)

Stage A - Primary/Acute HIV (2-6 weeks post-infection)

Flu-like illness: fever, lymphadenopathy, pharyngitis, rash, myalgias
High viral load, CD4 may temporarily drop
Self-limiting in most; some never notice it
Also called "acute retroviral syndrome"

Stage B - Chronic Asymptomatic/Symptomatic Phase

Can last 8-10 years without ART
Virus replicates slowly; CD4 gradually declines
Symptomatic stage B: oral candidiasis, hairy leukoplakia, recurrent herpes zoster, pelvic inflammatory disease, peripheral neuropathy

Stage C - AIDS

Defined by:

CD4+ count < 200 cells/μL, OR
Presence of an AIDS-defining illness (opportunistic infection or malignancy)

AIDS-defining illnesses include:

Category	Examples
Fungi	PCP (Pneumocystis jirovecii pneumonia), esophageal candidiasis, cryptococcosis, histoplasmosis
Viruses	CMV retinitis, HSV (chronic ulcers >1 month), PML (JC virus)
Bacteria	Mycobacterium avium complex, disseminated TB
Parasites	Toxoplasmosis of brain, cryptosporidiosis
Malignancies	Kaposi's sarcoma, Burkitt's lymphoma, primary CNS lymphoma
Other	HIV encephalopathy, HIV wasting syndrome, invasive cervical cancer

Harrison's Principles of Internal Medicine 22E (2025), Table 208-1

7. Diagnosis

Test	Use
4th-generation HIV Ag/Ab combo test	Initial screening; detects p24 antigen + antibodies
HIV RNA (viral load)	Confirms acute infection; monitors treatment response
CD4+ count	Assesses immune status; guides OI prophylaxis
Western blot / confirmatory assay	Confirms positive screening test
HIV resistance genotype	Before starting ART; guides drug selection

Target on ART: Viral load < 50 copies/mL (undetectable)

8. Treatment - Antiretroviral Therapy (ART)

ART is recommended for all people living with HIV, initiated as soon as possible after diagnosis.

Drug Classes and Targets:

Class	Mechanism	Examples
NRTIs (Nucleoside RT inhibitors)	Block reverse transcription	Tenofovir (TDF/TAF), emtricitabine (FTC), lamivudine (3TC), abacavir (ABC)
NNRTIs (Non-nucleoside RT inhibitors)	Block RT allosterically	Efavirenz, rilpivirine, doravirine
INSTIs (Integrase inhibitors)	Block viral DNA integration	Dolutegravir (DTG), bictegravir (BIC), raltegravir
PIs (Protease inhibitors)	Block viral maturation	Darunavir, atazanavir
Entry/fusion inhibitors	Block gp120-CD4 binding or CCR5	Maraviroc (CCR5 antagonist), enfuvirtide

Preferred first-line regimens (2025):

Bictegravir/TAF/FTC (single pill, once daily) - preferred for most patients
Dolutegravir + TAF/FTC
Dolutegravir/lamivudine (2-drug regimen, if HIV RNA <500,000 and CD4 >200, no HBV)
2025 DHHS ART guidelines; Harrison's Principles of Internal Medicine 22E (2025)

9. Prevention

Strategy	Details
PrEP (Pre-exposure prophylaxis)	Tenofovir-based regimen for high-risk individuals; >99% effective when taken correctly
nPEP (Nonoccupational post-exposure)	TDF/FTC + dolutegravir for 28 days; must start within 72 hours of exposure
Condoms	Effective barrier against sexual transmission
PMTCT	ART in pregnancy; cesarean before labor/membrane rupture reduces vertical transmission
Needle exchange programs	Reduces parenteral transmission
Viral suppression	Undetectable = Untransmittable (U=U) - confirmed by landmark studies

10. Key Numbers to Remember

Parameter	Value
Normal CD4 count	500-1500 cells/μL
AIDS threshold	CD4 < 200 cells/μL
Start PCP prophylaxis	CD4 < 200 cells/μL
Start MAC prophylaxis	CD4 < 50 cells/μL
ART target viral load	< 50 copies/mL
nPEP window	Within 72 hours
Acute HIV window period	2-6 weeks post-exposure

Sources: Robbins & Kumar Basic Pathology (9th ed.), Harrison's Principles of Internal Medicine 22E (2025, McGraw Hill), Washington Manual of Medical Therapeutics

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