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HIV Infection

High EvidenceUpdated: 2025-12-24

On This Page

Red Flags

  • Low CD4 less than 200 (Risk of Opportunistic Infection)
  • Severe Headache (Cryptococcal Meningitis?)
  • Visual Changes (CMV Retinitis?)
  • Shortness of Breath (PCP Pneumonia?)
Overview

HIV Infection

1. Clinical Overview

Summary

Human Immunodeficiency Virus (HIV) is a retrovirus that infects and destroys CD4+ T-lymphocytes, leading to progressive immune failure. Without treatment, it advances to Acquired Immunodeficiency Syndrome (AIDS). The introduction of Antiretroviral Therapy (ART) has transformed HIV from a fatal diagnosis into a manageable chronic condition with a near-normal life expectancy. [1,2]

U=U (Undetectable = Untransmittable)

This is a foundational concept in modern HIV medicine. A patient on effective treatment with a consistently undetectable viral load cannot sexually transmit the virus to others.

Clinical Pearls

Seroconversion Illness: 50-70% of patients experience a flu-like illness 2-4 weeks after infection (Fever, Rash, Lymphadenopathy, Sore Throat). It mimics Glandular Fever (Mononucleosis). "HIV is the syphilis of the viral world" - always test for HIV in any adult with severe "viral sore throat".

Indicator Conditions: Conditions that should prompt an HIV test:

  • Shingles (in a young person).
  • Seborrhoeic Dermatitis (severe/resistant).
  • Oral Candida.
  • Hairy Leukoplakia.
  • Unexplained weight loss / lymphadenopathy.
  • Pneumocystis Pneumonia (PCP).

Immune Reconstitution Inflammatory Syndrome (IRIS): When you start ART in a patient with very low CD4 count, their immune system "wakes up" and mounts a massive inflammatory response against existing opportunistic infections (e.g., TB), causing the patient to initially deteriorate.

2. Epidemiology

Demographics

  • Prevalence: 38 million people living with HIV globally.
  • UK Epidemiology: Major groups affected are MSM (Men who have sex with Men) and Black African heterosexuals (though heterosexual acquisition is rising).
  • Transmission: Sexual (Anal > Vaginal), Blood (IVDU), Vertical (Mother-to-Child).
3. Pathophysiology

Lifecycle of the Retrovirus

  1. Binding: HIV gp120 binds to CD4 receptor and CCR5/CXCR4 co-receptor.
  2. Reverse Transcription: HIV RNA is converted to DNA by Reverse Transcriptase.
  3. Integration: Viral DNA enters nucleus and is spliced into host DNA by Integrase.
  4. Replication: Host machinery transcribes viral RNA.
  5. Maturation: Protease cleaves viral proteins to form new virions.

Immunodeficiency

  • CD4 cells are "The General" of the immune army.
  • As CD4 count falls:
    • >500: Asymptomatic.
    • 200-500: Minor infections (Shingles, Thrush).
    • less than 200 (AIDS): Major Opportunistic Infections (PCP, Toxoplasmosis).
4. Clinical Presentation

Phases

  1. Primary Infection (Seroconversion):
    • Fever, Maculopapular rash, Pharyngitis.
    • High viral load, Negative antibody (Window period).
  2. Clinical Latency (Years):
    • Asymptomatic.
    • Ongoing viral replication and CD4 decline.
  3. Symptomatic HIV:
    • Night sweats, weight loss, lymphadenopathy.
  4. AIDS:
    • Defining illnesses (Kaposi, PCP, TB, Lymphoma).
5. Clinical Examination
  • Mouth: Oral Thrush? Oral Hairy Leukoplakia? (EBV driven white ridges on side of tongue).
  • Skin: Kaposi Sarcoma (Purple nodules)? Seborrhoeic Dermatitis? Pruritic Papular Eruption?
  • Nodes: Generalised Lymphadenopathy (PGL).
  • Abdomen: Hepatosplenomegaly.
6. Investigations

Diagnosis

  • HIV Antigen/Antibody Combo Test (4th Gen): Standard screening. Detects p24 Antigen (early) and Antibody. Window period ~4 weeks.
  • Point of Care (Fingerprick): Antibody only. Window period ~12 weeks.
  • Viral Load (PCR): Confirmation and Monitoring.

Baseline Assessment

  • CD4 Count: Staging.
  • Resistance Genotyping: To guide drug choice.
  • HLA-B*5701: Check before using Abacavir (Risk of fatal hypersensitivity).
  • Co-infection Screen: Hep B, Hep C, Syphilis, TB (Quantiferon).
7. Management

Management Algorithm

        HIV CONFIRMED
             ↓
    BASELINE INVESTIGATIONS
   (CD4, VL, Resis, HLA-B*5701)
             ↓
    INITIATE ART (IMMEIDATELY)
   ("Test and Treat" strategy)
             ↓
     STANDARD REGIMEN
   (2 NRTIs + 1 Integrase Inhib)
   e.g. Tenofovir + Emtricitabine
        + Dolutegravir
             ↓
   MONITOR EFFECTIVENESS
   - Viral Load at 1/3/6 months
   - Target: less than 50 copies/ml
   - If fail: Check Compliance

Antiretroviral Therapy (ART)

Standard is Triple Therapy (HAART).

  1. Backbone: 2 NRTIs (Nucleoside Reverse Transcriptase Inhibitors).
    • Tenofovir + Emtricitabine (Truvada).
    • Abacavir + Lamivudine (Kivexa).
  2. Anchor Drug: Usually an Integrase Inhibitor (INSTI).
    • Dolutegravir or Bictegravir.
    • Alternatively: NNRTI (Rilpivirine) or Protease Inhibitor (Darunavir/Ritonavir).

Prophylaxis (With CD4 less than 200)

  • Co-trimoxazole: To prevent PCP and Toxoplasmosis.
8. Complications

AIDS-Defining Illnesses

  • Respiratory: PCP (Pneumocystis jirovecii). Dry cough, hypoxia, normal CXR or bat-wing. Treat: Co-trimoxazole.
  • Neurology:
    • Toxoplasmosis: Space occupying lesions (Ring enhancing). Treat: Sulphadiazine/Pyrimethamine.
    • Cryptococcal Meningitis: High pressure. Treat: Amphotericin.
    • PML: JC Virus. White matter demyelination.
  • Malignancy:
    • Kaposi Sarcoma: HHV-8. Purple lesions.
    • Non-Hodgkin Lymphoma: EBV associated.
    • Cervical Cancer: HPV associated.
  • Gastro: Oesophageal Candidiasis.
9. Prognosis and Outcomes
  • Life Expectancy: Near normal if diagnosed early and adherent.
  • Late Diagnosis: Still carries high mortality (10x higher in first year).
10. Evidence and Guidelines

Key Guidelines

GuidelineOrganisationKey Recommendations
TreatmentBHIVA (UK) / DHHS (US)Start ART in EVERYONE regardless of CD4 count (START Trial).
TestingNICEOpt-out testing in EDs in high prevalence areas.

Landmark Evidence

1. START Trial

  • Showed immediate ART initiation (CD4 >500) reduces serious AIDS and non-AIDS events compared to deferring until CD4 less than 350.

2. PARTNER Study

  • Proved U=U. Zero transmissions in serodiscordant couples where positive partner had undetectable viral load.
11. Patient and Layperson Explanation

What is HIV?

It is a virus that attacks the immune system. If left untreated, it stops you fighting off infections.

Is it AIDS?

AIDS is the late stage when the immune system has already failed. Most people with HIV do not have AIDS and never will, provided they take treatment.

What is the treatment?

It is usually one or two tablets, once a day. You have to take them forever. The side effects are very few nowadays.

Can I transmit it?

Once the virus is "Undetectable" in your blood (usually takes 3-6 months of tablets), you cannot pass it on to sexual partners, even without condoms (though condoms stop other STIs). You can also have normal healthy children.

12. References

Primary Sources

  1. BHIVA Guidelines on the Management of HIV-1 Positive Adults. 2022.
  2. INSIGHT START Study Group. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015.
  3. Rodger AJ, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER). Lancet. 2019.
13. Examination Focus

Common Exam Questions

  1. Diagnosis: "Young man, flu-like illness, rash, negative Monospot?"
    • Answer: Acute HIV Seroconversion. Do 4th Gen Test.
  2. Safety: "Drug to check for before Abacavir?"
    • Answer: HLA-B*5701 (Hypersensitivity).
  3. Pathology: "Cause of ring enhancing lesions in brain?"
    • Answer: Toxoplasmosis (treat empirically to see if shrinks) vs Lymphoma.
  4. Pharmacology: "Mechanism of Tenofovir?"
    • Answer: Nucleotide Reverse Transcriptase Inhibitor (NRTI).

Viva Points

  • Post Exposure Prophylaxis (PEP): Truvada + Raltegravir for 28 days. Must start less than 72 hours (ideally less than 24).
  • PrEP: Pre-exposure prophylaxis. Truvada taken daily or "on demand" by high risk negative people prevents acquisition.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.

Last updated: 2025-12-24

At a Glance

EvidenceHigh
Last Updated2025-12-24

Red Flags

  • Low CD4 less than 200 (Risk of Opportunistic Infection)
  • Severe Headache (Cryptococcal Meningitis?)
  • Visual Changes (CMV Retinitis?)
  • Shortness of Breath (PCP Pneumonia?)

Clinical Pearls

  • **Indicator Conditions**: Conditions that should prompt an HIV test:
  • * Shingles (in a young person).
  • * Seborrhoeic Dermatitis (severe/resistant).
  • * Hairy Leukoplakia.
  • * Unexplained weight loss / lymphadenopathy.

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines