STEPTRACKERMICROBIOLOGY + IMMUNOLOGY | RETROVIRUSES | HIGH-YIELD REVIEW

HIV I — Virus, Diagnosis & Course

A diploid +RNA retrovirus that integrates into CD4⁺ cells — know each viral protein, each step of the life cycle (and the drug that blocks it), the testing algorithm and the natural history.

FOCUS ON

Genes: env → gp160 cleaved to gp120 (binds CD4 + coreceptor CCR5 early / CXCR4 late) and gp41 (fusion); gag → p24 capsid, p17 matrix; pol → reverse transcriptase, integrase, protease. CCR5 Δ32 homozygotes resist infection. Diagnosis: 4th-generation HIV-1/2 antigen (p24)/antibody immunoassay → HIV-1/HIV-2 differentiation assay → HIV RNA if discordant; infants of HIV ⁺ mothers need PCR (maternal IgG crosses placenta). Course: acute retroviral syndrome → clinical latency → AIDS (CD4 < 200 or AIDS-defining illness). Viral load predicts progression; CD4 predicts opportunistic risk.

TOPIC

DETAIL

CLINICAL RELEVANCE

DRUG OR TEST

Attachment

gp120 binds CD4, then CCR5 (macrophage-tropic) or CXCR4 (T-cell-tropic)

CCR5 Δ32 homozygotes protected

Maraviroc (CCR5 antagonist) · tropism assay first

Fusion

gp41 drives membrane fusion

—

Enfuvirtide

Reverse transcription

RT (error-prone) makes dsDNA from RNA

High mutation rate → resistance

NRTIs, NNRTIs

Integration

Integrase inserts proviral DNA into host genome

Latent reservoir in resting memory T cells → no cure

Integrase inhibitors (-tegravir)

Maturation

Protease cleaves gag-pol polyprotein

Immature virions not infectious

Protease inhibitors (-navir)

Accessory genes

tat (transcription), rev (RNA export), nef (↓ MHC I), vpu, vif (blocks APOBEC3G)

Immune evasion

—

Transmission

Sex (anal receptive highest), needles, perinatal, breast milk, transfusion

Risk ↑ with high viral load and genital ulcers

PrEP (tenofovir-based, cabotegravir) · PEP within 72 h for 28 days

Screening test

4th-gen antigen/antibody immunoassay (p24 appears ~2 weeks)

Shorter window than antibody-only tests

Screen everyone 15–65 at least once

Confirmation

HIV-1/HIV-2 antibody differentiation immunoassay; HIV RNA (NAT) if negative/indeterminate

Western blot no longer used

—

Infant diagnosis

Maternal IgG present up to 18 months

Antibody tests falsely ⁺

HIV DNA/RNA PCR

Acute retroviral syndrome

2–4 weeks post-exposure; very high viral load

Mono-like: fever, pharyngitis, lymphadenopathy, rash, oral ulcers

Antibody may be negative → HIV RNA

Clinical latency

Viral set point; ongoing replication in lymph nodes; CD4 falls ~50–100/year

Generalized lymphadenopathy, few symptoms

Start ART for everyone at diagnosis

AIDS

CD4 < 200/µL or AIDS-defining illness

Opportunistic infections, cancers, wasting, dementia

See 7.07

Monitoring

Viral load (treatment response) and CD4 (immune status, prophylaxis)

Goal: undetectable load → no sexual transmission

Genotype resistance testing before ART

Picture it — HIV structure and natural history

The virionEnvelope glycoproteins gp120/gp41 sit in host-derived lipid; the conical p24 capsid holds two RNA copies plus reverse transcriptase, integrase and protease.

Untreated courseViral load spikes in acute infection, falls to a set point, then rises; CD4 dips, partly recovers and declines over years until it crosses 200.

Schematic diagrams, not to scale.

Mechanism — life cycle and drug targets

Bind CD4 + CCR5Maraviroc

→

Fuse (gp41)Enfuvirtide

→

Reverse transcribeNRTI, NNRTI

→

IntegrateIntegrase inhibitors

→

Cleave polyproteinProtease inhibitors

HIV proteins

GENE

PRODUCT

ROLE

env

gp120, gp41

Attachment, fusion

gag

p24, p17

Capsid (in 4th-gen test), matrix

pol

RT, integrase, protease

Drug targets

nef

Nef

↓ MHC I, faster progression

vif

Vif

Degrades APOBEC3G

How it's tested

COMMON CONFUSIONAcute HIV vs EBV mono — both febrile pharyngitis with adenopathy; HIV adds mucocutaneous ulcers and rash and needs an RNA test because antibodies lag.

THE TRAPA positive antibody test in a 6-month-old of an HIV ⁺ mother may be maternal IgG — use PCR.

YOUR APPROACHExposure → stage (acute, latent, AIDS) → right test (Ag/Ab, RNA, PCR) → viral load and CD4 → ART and prophylaxis.

If you see… think…

HIV attachment protein → gp120 (CD4 + CCR5/CXCR4)

HIV fusion protein → gp41

Antigen detected by 4th-generation test → p24 capsid

Person repeatedly exposed but never infected → CCR5 Δ32 homozygous

Fever, rash, oral ulcers 3 weeks after unprotected sex, antibody negative → acute HIV (check RNA)

Test for HIV in an exposed infant → PCR

Why HIV can't be cured → integrated latent reservoir

Defines AIDS by count → CD4 < 200/µL

Best marker of treatment response → viral load

Must be checked before starting maraviroc → CCR5 tropism