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HIV & AIDS

High EvidenceUpdated: 2025-12-24

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Red Flags

  • New Seizure / Focal Neurology (Toxoplasmosis / CNS Lymphoma)
  • Severe Breathlessness + Dry Cough (PCP)
  • Visual Loss (CMV Retinitis)
  • Severe Headache (Cryptococcal Meningitis)
Overview

HIV & AIDS

1. Clinical Overview

Summary

Human Immunodeficiency Virus (HIV) is a lentivirus that depletes CD4+ T-helper cells, leading to severe immunodeficiency. Without treatment, it progresses to AIDS (Acquired Immunodeficiency Syndrome), defined by a CD4 count less than 200 or the presence of an AIDS-defining illness. With modern Antiretroviral Therapy (ART), HIV is a chronic manageable condition with near-normal life expectancy. The principle of U=U (Undetectable = Untransmittable) is central to modern management. [1,2]

Clinical Pearls

Seroconversion Illness: "The Great Mimic". 60-80% of patients develop a glandular-fever like illness (Fever, Rash, Sore Throat, Lymphadenopathy) 2-6 weeks after exposure. Always test for HIV in any adult presenting with "Glandular Fever" who tests negative for EBV (Monospot).

Indicator Conditions: Be alert to "Red Flag" presentations that warrant an HIV test:

  • Shingles in a young person.
  • Oral Thrush without inhaler/antibiotic use.
  • Seborrhoeic Dermatitis (severe/sudden onset).
  • Oral Hairy Leukoplakia (EBV on lateral tongue).
  • Thrombocytopenia (ITP).

IRIS (Immune Reconstitution Inflammatory Syndrome): A paradoxical worsening of an opportunistic infection (e.g., TB or Cryptococcus) after starting ART, as the waking immune system attacks the pathogens. Pearl: In TB-HIV co-infection, treat the TB first for 2-8 weeks before starting ART to reduce IRIS risk.


2. Epidemiology

Transmission

  • Sexual: The main route. Risk per act is low (~0.1-1%) but cumulative.
  • Parenteral: Needlestick (0.3% risk), IV Drug Use.
  • Vertical: Mother-to-Child (In utero, delivery, breastfeeding). Risk reduced from 25% to less than 0.5% with ART.

3. Pathophysiology

Mechanism

  1. Entry: HIV gp120 binds to the CD4 receptor and co-receptors (CCR5 or CXCR4) on T-Helper cells.
  2. Reverse Transcription: Viral RNA is converted to DNA by Reverse Transcriptase (error prone -> mutations).
  3. Integration: Viral DNA enters the nucleus and integrates into host DNA (Integrase enzyme).
  4. Replication: The cell produces new virions, which bud off and kill the host cell.
  5. Immunodeficiency: Progressive loss of CD4 cells compromises Cell-Mediated Immunity.

4. Differential Diagnosis
ConditionPresentationKey Features
SeroconversionFever, Rash, Sore Throatp24 Ag Positive, HIV Ab Neg/Pos.
Glandular Fever (EBV)Fever, Rash, Sore ThroatMonospot Positive. Atypical Lymphocytes.
Secondary SyphilisRash (Palms/Soles)VDRL/TPPA Positive.
Lyme DiseaseErythema MigransTick bite history.

5. Clinical Presentation

Staging

Common AIDS-Defining Illnesses


Primary HIV
Seroconversion illness (viral load very high).
Latent Phase
Asymptomatic (Clinical Latency). Can last 10 years. CD4 count drops by ~50-80/year.
Symptomatic HIV
CD4 less than 500. Thrush, Hairy leukoplakia, Shingles, Weight loss.
AIDS
CD4 less than 200. Opportunistic Infections (OIs) and Malignancies.
6. Investigations

Screening

  • 4th Generation HIV Test: Detects HIV Antibody AND p24 Antigen.
    • Window Period: 45 days (Reliable at 4 weeks, Definite at 12 weeks).
  • Rapid Point of Care: Finger prick (Antibody only). Window period is longer (90 days).

Baseline for Positives

  • CD4 Count: Normal 500-1500.
  • Viral Load: Target less than 20 (Undetectable).
  • Resistance Testing: Determining drug susceptibility (Genotypic).
  • HLA-B*5701: Must check before using Abacavir (Hypersensitivity risk).

7. Management

Management Algorithm

        HIV POSITIVE DIAGNOSIS
                ↓
    START ANTIRETROVIRAL THERAPY (ART)
    (Recommended for ALL CD4 counts
     to prevent transmission/damage)
                ↓
    STANDARD REGIMEN (Triple Therapy)
    • Backbone: 2 x NRTIs
      (e.g. Tenofovir + Emtricitabine)
    • Anchor: 1 x Integrase Inhibitor
      (e.g. Dolutegravir)
    • Often Single Tablet Regimen (e.g., Biktarvy)
                ↓
    MONITORING
    • Viral Load (Aim: Undetectable less than 6 months)
    • CD4 Count (Should rise)
    • Comorbidities (CV Risk, Renal, Bone)

Prophylaxis (Primary)

  • Co-trimoxazole 960mg OD:
    • Start if CD4 < 200.
    • Prevents PCP (Pneumocystis) and Toxoplasmosis.

Prevention

  • PrEP (Pre-Exposure Prophylaxis): Tenofovir/Emtricitabine taken by HIV-negative people at risk. Highly effective (>99%).
  • PEP (Post-Exposure Prophylaxis): 28 day course of Triple Therapy. Start less than 72h (the sooner the better).

8. Complications
  • Opportunistic Infections: (See Presentation).
  • Metabolic: ART (especially older generations) linked to Dyslipidaemia, Lipodystrophy, and Insulin Resistance.
  • Renal: HIV-Associated Nephropathy (HIVAN). Tenofovir can cause tubular toxicity.
  • Bone: Osteopenia/Osteoporosis common.

9. Prognosis and Outcomes
  • Life Expectancy: A 20-year-old starting ART today has a near-normal life expectancy.
  • Late Diagnosis: Still carries high mortality (10x higher in first year) due to presenting with advanced OIs.

10. Evidence and Guidelines

Key Guidelines

GuidelineOrganisationKey Recommendations
HIV TreatmentBHIVA (UK)"Test and Treat" (Start ART immediately).
PrEPBASHHGuidelines for prescribing/monitoring PrEP.

Landmark Evidence

1. START Trial (NEJM 2015)

  • Proved that starting ART immediately (CD4 >500) is superior to deferring until CD4 less than 350. Reduced AIDS events and non-AIDS events (cancer/CV). Changed global guidelines to "Treat All".

2. PARTNER Studies (Lancet)

  • Established the U=U consensus. Zero transmissions in thousands of condomless sex acts where the positive partner was undetectable.

11. Patient and Layperson Explanation

What is HIV?

It is a virus that attacks your immune system cells (CD4 cells). If untreated, it depletes these cells until your body cannot fight off simple infections. This late stage is called AIDS.

The Good News

Although we can't fully "cure" it (remove it from the body completely), we have excellent medication that puts the virus to sleep. Taking one or two tablets a day stops the virus reproducing.

Can I pass it on?

Not if your treatment is working. Once the virus levels in your blood become "Undetectable" (usually after 3-6 months of treatment), you cannot pass the virus to sexual partners, even without condoms. This is called U=U (Undetectable = Untransmittable).

What is the outlook?

Normal. You can work, travel, have relationships, and have healthy children (who will be HIV negative). You just have to take the tablets every day.


12. References

Primary Sources

  1. British HIV Association (BHIVA). Guidelines for the treatment of HIV-1-positive adults. 2022.
  2. The 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: "Window period for 4th Gen test?"
    • Answer: 45 days (4 weeks is good, 6 weeks definitive).
  2. Safety: "Drug causing hypersensitivity?"
    • Answer: Abacavir (Test HLA-B*5701).
  3. Prophylaxis: "Drug for CD4 less than 200?"
    • Answer: Co-trimoxazole (Septrin).
  4. Pathology: "Cause of ring enhancing brain lesions?"
    • Answer: Toxoplasmosis.

Viva Points

  • PCP Presentation: Remember the "Walk Test" - O2 sats drops on exertion. LDH is elevated. Treated with Co-trimoxazole (NOT Penicillin).
  • IRIS: Why do we delay ART in TB Meningitis? To prevent a catastrophic inflammatory reaction in the brain (IRIS) which could be fatal. We treat the TB first.

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

  • New Seizure / Focal Neurology (Toxoplasmosis / CNS Lymphoma)
  • Severe Breathlessness + Dry Cough (PCP)
  • Visual Loss (CMV Retinitis)
  • Severe Headache (Cryptococcal Meningitis)

Clinical Pearls

  • **Indicator Conditions**: Be alert to "Red Flag" presentations that warrant an HIV test:
  • - **Shingles** in a young person.
  • - **Oral Thrush** without inhaler/antibiotic use.
  • - **Seborrhoeic Dermatitis** (severe/sudden onset).
  • - **Oral Hairy Leukoplakia** (EBV on lateral tongue).

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines