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Human Immunodeficiency Virus (HIV) Infection and AIDS

Table of Contents

  • Introduction
  • Epidemiology
  • Aetiology and Pathophysiology
  • Natural History
  • Transmission
  • Risk Factors
  • Clinical Features
  • Investigations
  • Management
  • Complications
  • References
  • Related Notes
  • Test Yourself

Key Points ⚡

  • HIV is a lentivirus infecting CD4+ T helper lymphocytes, causing progressive immune destruction and AIDS.
  • HIV-1 is predominant in the UK; global new diagnoses and HIV-related deaths are declining.
  • Transmission occurs via infected bodily fluids (sexual, blood, vertical), not by casual contact or vectors.
  • Antiretroviral therapy (ART) targets multiple stages of viral replication: binding, fusion, reverse transcription, integration, assembly, budding.
  • Primary HIV infection (seroconversion) occurs 2-4 weeks post-exposure with nonspecific symptoms.
  • AIDS is defined by CD4+ count <200 cells/μL or presence of AIDS-defining illnesses (e.g., Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma).
  • Diagnosis primarily via 4th generation HIV tests (antibody + p24 antigen).
  • Early initiation of ART is critical; prophylaxis (PrEP/PEP) for at-risk groups.
  • Regular monitoring of CD4+ count and viral load guides treatment and prognosis.

Introduction

  • HIV causes progressive immune dysfunction through destruction of CD4+ T helper cells.
  • Despite global advances, HIV/AIDS remain significant health and economic burdens.
  • UK has met UNAIDS 90-90-90 goals for diagnosis, treatment, and viral suppression.

Epidemiology

  • HIV-1 is the main virus in the UK; HIV-2 mainly found in West Africa.
  • Significant reductions in incidence and mortality over recent years globally and in the UK.
  • High prevalence among men who have sex with men (MSM) and black-African heterosexual populations.

Aetiology and Pathophysiology

HIV Life Cycle and Drug Targets

  1. Binding: gp120 on HIV binds CD4 and co-receptors CCR5 or CXCR4 (blocked by CCR5 antagonists).
  2. Fusion: gp41 mediates fusion of viral and cell membranes (blocked by fusion inhibitors).
  3. Reverse Transcription: Viral RNA → DNA by reverse transcriptase (blocked by NRTIs and NNRTIs).
  4. Integration: Viral DNA integrates into host genome via integrase (blocked by integrase inhibitors).
  5. Replication: Host machinery produces viral components.
  6. Assembly: New viral components assemble at cell membrane.
  7. Budding: Virions bud and mature by protease cleavage (blocked by protease inhibitors).

Natural History

  • Stage 1: Primary HIV Infection (Seroconversion)
  • Occurs 2-4 weeks after exposure, with high viral replication and infectiousness.

  • Symptoms resemble viral illness (fever, malaise, rash, pharyngitis).

  • Stage 2: Clinical Latency (Chronic HIV Infection)

  • Virus persists at low levels; patients mostly asymptomatic but infectious.

  • Lasts 10-15 years or longer.

  • Stage 3: AIDS

  • CD4+ count <200 cells/μL or AIDS-defining illnesses appear.
  • Severe immunodeficiency with opportunistic infections and malignancies.
  • Untreated AIDS leads to death within ~20 months.

Transmission

  • Sexual contact (vaginal, anal, oral) accounts for ~75% of cases globally.
  • Vertical transmission during pregnancy, childbirth, or breastfeeding.
  • Blood exposure: contaminated needles, transfusions, occupational.
  • No transmission via casual contact, vectors, or saliva without oral pathology.

Risk Factors

  • MSM and female partners of MSM.
  • Individuals from high-prevalence regions.
  • Serodiscordant couples.
  • IV drug use and needle sharing.
  • Unprotected sex and coexisting STIs.
  • Occupational exposures (e.g., needlestick injuries).

Clinical Features

Primary HIV Infection

  • Fever (80%), malaise, arthralgia, rash, pharyngitis, oral ulcers, weight loss.
  • Symptoms nonspecific, often mistaken for other viral illnesses.

Longstanding HIV Infection

System Symptoms/Signs
Constitutional Fever, weight loss, sweats
Hematology Lymphadenopathy, neutropenia, anemia, thrombocytopenia
Respiratory Cough, pneumonia (e.g., Pneumocystis jirovecii)
Neurological Confusion, seizures, personality changes
Oral Candidiasis, hairy leukoplakia, ulcers
Gastrointestinal Diarrhea
Dermatological Kaposi’s sarcoma lesions, fungal infections, warts, shingles
Genito-urinary Candidiasis, herpes simplex
Malignancy Non-Hodgkin’s lymphoma, primary CNS lymphoma

AIDS-defining Illnesses

  • Pneumocystis jirovecii pneumonia
  • Cryptococcal meningitis
  • Toxoplasmosis
  • CMV retinitis
  • Kaposi’s sarcoma
  • Non-Hodgkin’s lymphoma
  • Esophageal candidiasis
  • Tuberculosis

Investigations

  • Testing Guidelines: NICE recommends testing at-risk groups, antenatal screening, STI clinics, and based on clinical suspicion.
  • Tests:
  • 4th generation assays (detect HIV antibodies and p24 antigen) – standard diagnostic test.
  • 3rd generation point-of-care tests (detect antibodies) – quicker but higher false positives.
  • Confirmatory testing required after positive initial test.
  • Window period: Negative test within 90 days post-exposure requires repeat testing.
  • Pre- and post-test counselling essential for patient understanding and support.

Management

Antiretroviral Therapy (ART)

  • Combination therapy with at least three active drugs from different classes to prevent resistance.
  • Common regimen backbone: two nucleoside reverse transcriptase inhibitors (e.g., tenofovir disoproxil + emtricitabine) + integrase inhibitor or NNRTI or boosted protease inhibitor.
Drug Class Examples
NRTIs Emtricitabine, Tenofovir, Abacavir, Lamivudine
NNRTIs Efavirenz, Nevirapine, Rilpivirine
Protease Inhibitors Atazanavir, Darunavir, Ritonavir
Integrase Inhibitors Dolutegravir, Elvitegravir, Raltegravir
CCR5 Antagonist Maraviroc
Fusion Inhibitor Enfuvirtide
  • Treatment modification may be needed for toxicity, resistance, or side effects.
  • Adverse effects include renal impairment, hepatotoxicity, neuropathy, bone marrow suppression, pancreatitis.

Prophylaxis

  • Pre-exposure prophylaxis (PrEP): Daily tenofovir disoproxil + emtricitabine for high-risk HIV-negative individuals.
  • Post-exposure prophylaxis (PEP): Emergency treatment started within 72 hours of exposure, continued for 28 days; commonly tenofovir disoproxil + emtricitabine + raltegravir.

Monitoring and Support

  • Regular CD4+ count and viral load testing (every 3-6 months early, 2-3 months late disease).
  • Support services: HIV charities, safer injection programs, counselling on adherence and safe sex practices.
  • British HIV Association endorses "Undetectable = Untransmittable (U=U)" principle.

Complications

System Illness / Description
Respiratory Pneumocystis jirovecii pneumonia (most common opportunistic infection)
Gastrointestinal Chronic diarrhoea, hepatomegaly due to viral hepatitis or drugs
Neurological Meningoencephalitis, toxoplasmosis, primary CNS lymphoma
Dermatological Kaposi’s sarcoma, fungal infections, herpes simplex, warts

Prognosis

  • Life expectancy improved with ART but still lower than general population.
  • Early ART initiation and adherence crucial to prevent progression and resistance.
  • Viral suppression usually achieved within 3-6 months of treatment.

References

  • Avert (2019) HIV and AIDS in the United Kingdom.
  • NICE (2018) HIV infection and AIDS guidelines.
  • British HIV Association (2018) Adult HIV Testing Guidelines.
  • CDC and UNAIDS official publications.
  • Chickenpox (VZV)
  • Human Papillomavirus (HPV) and Genital Warts
  • Kaposi’s Sarcoma
  • Oral Hairy Leukoplakia

Test Yourself

  • [Link to clinical case questions and HIV MCQs]

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