Pathology of HIV infection

Pathology of HIV infection

Updated: 08/07/2025

© Jun Wang, MD, PhD

 

General features

  • Most commonly caused by HIV-1
  • HIV-2 infection rare and usually with mild clinical presentations
  • Transmitted through sexual activities, shared intravenous drug equipment, or mother to child (transplacental or milk)
  • Targeting CD4+ cells: T helper, thymocytes, granulocytes, macrophages, Langerhans cells, dendritic cells
  • B cells are also reduced in number and could be dysfunctional 
  • Causes immune dysfunction or hyperactivation
  • Disrupted immune system results in higher risks of infections, especially opportunistic infections, and certain neoplasia (AIDS)

Major risk of HIV infection

  • Blood-borne
    • Needle-sharing IV drug usage: High risk
    • Blood transfusion, needle stick, mucosal exposure to blood: usually low risk in America
  • Sexual exposure

Key HIV components and their functions

  • Structural

o   GP120: binding CD4

o   GP41: Anchoring GP120 to viral envelop, penetrating host cell membrane for entry of viral RNA, one target of anti-retroviral therapy

o   P24: protein on viral capsid, elevated in serum within weeks of infection, target of diagnostic test by ELISA

  • Enzymes

o   Reverse transcriptase: encoded by the pol gene, RNA-dependent DNA polymerase, one target of antiretroviral therapy by Zidovudine (AZT), Stavudine, etc

o   Protease: encoded by the gag-pol gene, one target of antiretroviral therapy: Amprenavir, Darunavir, etc

o   Integrase: integrate dsDNA into host genome, one target of antiretroviral therapy: Raltegravir, Dulutegravir

HIV life cycle

  • Viral entry factors: gp120/gp41 complex
  • Viral gp120 binding CD4
  • CD4-gp120 complex binding to chemokine receptor (CCR-5)
  • Viral gp41 penetrates host cell membrane
  • HIV RNA entering host cells
  • Reverse transcriptase activated, provirus DNA produced
  • Provirus DNA integrated into host genome
  • Transcription of viral RNA and production of viral proteins
  • Virion released from host cells

Pathogenesis


Stages of HIV infection

  • Stage 2: Chronic HIV infection
    • HIV multiply at very low levels, with relatively stable viral level and a progressive decline in the CD4 cell count
    • CD4+ lymphocytes may decline even with ART 
    • May develop to AIDS in 8-10 year without ART
    • Asymptomatic or clinical latency
    • May present with persistent generalized lymphadenopathy
    • P24 might disappear, but HIV antibody is usually positive
    • Stable p24 antibody levels, until later phase when immune function is significantly impaired
    • Other immune disorders may occur, including Guillian-Barrè syndrome, Reiter's syndrome, idiopathic thrombocytopenia, Sjögren's syndrome, etc
    • Higher risk for various conditions including candidiasis, hairy leukoplakia and seborrheic dermatitis
  • Stage 3: AIDS
    • 10 years or longer after stage 2
    • CD4+ T cells < 200/mcl (normal 500-1500/mcl)
    • High blood HIV and risk of transmission
    • AIDS defining conditions, including opportunistic infections and certain neoplasms

Screening recommendations

  • All adolescents and adults with increased risk of HIV infection, pregnant women (The US Preventive Services Task Force)
  • People at high risk for HIV infection (annually, CDC)
  • Routine screening encouraged (American College of Physicians)
  • Commonly started with immunoassay for p24 and HIV antibodies
  • Molecular test for HIV RNA if early infection is strongly suspected, and the immunoassay is negative, since HIV RNA elevate before the presence of p24 and HIV antibodies

Blood markers

  • HIV-1/2 antigen (p24)/antibody: weeks after infection, later phase of early infection
  • HIV RNA: elevate before presence of p24 and antibodies, early phase of early infection

Screening tests

  • HIV-1/2 antigen (p24)/antibody immunoassay

Confirmation tests

  • HIV-1/2 antibody differentiation immunoassay
  • HIV-1/2 nucleic acid test

Commonly seen opportunistic infections

Other disorders associated with HIV

Managements

  • Antiretroviral treatment
    • Fusion/uptake inhibitors: Enfuvirtide(binds to gp41), Maraviroc (block CCR5)
    • Inhibit reverse transcriptase: Zidovudine, Tenofovir, etc 
    • Inhibit HIV protease: Atazanavir, Darunavir, etc
    • Inhibit integrase: Raltegravir, dolutegravir 
  • Treatment of infections
  • Treatment of complication

Comments

Post a Comment

Popular posts from this blog

Contents

Pathology notes Jun Wang, MD, PhD 1. General information Frequently discussed syndromes Terms of dermatology Terms of hematology 2. Immunodeficiency disorders HIV infection   Primary immunodeficiency disorders 3. Hemodynamic abnormalities Shock Thrombosis and embolism Bleeding disorders Blood transfusion 4.  Benign blood cell disorders Anemia Benign white cell disorders 5. Hematopoietic neoplasms Lymphoid neoplasms Myeloid neoplasms Histiocytic neoplasms: Langerhans cell histiocytosis 6. Cardiovascular system Pulmonary hypertension Cardiovascular system tumors 7. Respiratory tract tumors 8. Gastrointestinal tract Congenital disorders Infectious gastroenteritis Oral cavity Esophagus Stomach Intestinal tumors Salivary glands Exocrine pancreas and gallbladder 9. Urinary system Kidney masses Lower urinary tract 10. Male reproductive system 11. Female genital tract 12. Breast 13. Endocrine organs Pituitary gland Ad...
Read more

Anemia

Anemia Updated: 07/13/2024 © Jun Wang, MD, PhD   General features Decrease in red cell mass Hemoglobin: Levels of hemoglobin in a specific volume of whole blood Hematocrit: Fraction of whole blood composed of red blood cells Red cell count: Quantity of red cell in a specific volume of whole blood Three major groups based on RBC sizes Microcytic Normocytic Macrocytic Three major causes Blood loss: acute or chronic Increased red cell destruction: hemolysis Reduced production: marrow failure due to genetic abnormality or nutritional deficiency Etiology Genetic abnormality Hemoglobinopathies RBC cytoskeletal abomorlities Enzyme abnormalities Fanconi anemia Nutritional deficiencies: iron, VB12, folate, general malnutrition Physical etiologies: trauma, burns, frostbite, prosthetic valves, etc Chronic diseases: chronic infections, neoplasia, autoimmune disorders, kidney or liver diseases, etc Infectious diseases: hepatitis, sepsis , malaria, e...
Read more

Myeloid neoplasms

Myeloid neoplasms Updated: 08/12/2024 © Jun Wang, MD, PhD General features Clonal diseases of hematopoietic stem or progenitor cells of the granulocytic (neutrophil, eosinophil, basophil), monocytic/macrophage, erythroid, megakaryocytic and mast cell lineages 8 large groups Acute myeloid leukemia (AML) Myelodysplastic syndrome (MDS) Myeloproliferative neoplasms (MPN) Myelodysplastic and myeloproliferative neoplasm(MDS/MPN) Mastocytosis Secondary myeloid neoplasms Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions Acute leukemias of mixed or ambiguous lineage Diagnostic approaches CBC and differential: Presence of blasts and immature cells, quantity based diagnosis Bone marrow aspiration and biopsy: Morphology and quantity of neoplastic cells and blasts component Immunophenotyping: Multiparameter flow cytometry Histochemical studies: Myeloperoxidase for myeloid Cytogenetics studies: Karyotype, FISH  Molecular studies La...
Read more