Makindo Medical Notes

Related Subjects: |AIDS (HIV) Neurological Disease |AIDS (HIV) Respiratory disease |AIDS Dementia Complex (HIV) |AIDS HIV Infection |AIDS(HIV) Gastrointestinal Disease |Acute Retroviral Syndrome (HIV) |HIV and Post-Exposure Prophylaxis (PEP) |HIV and Pre-exposure prophylaxis |HIV associated nephropathy (HIVAN) |HIV disease Assessment |Immune Reconstitution Syndrome |AIDS HAART Antiretrovirals |Kaposi sarcoma (KS)

Many people who are living with HIV have no obvious signs and symptoms at all.

Introduction

• The prognosis of HIV/AIDS is much improved. Those who do poorly are typically individuals whose CD4 count has fallen significantly before diagnosis and initiation of therapy.
• Early diagnosis is key. Starting HAART at the right time is crucial. Major causes of death nowadays include coronary artery disease, liver failure (often co-infection with Hepatitis B/C), and lymphoma.
• HAART revolutionized HIV/AIDS management, transforming it from a terminal illness into a chronic, manageable disease. It has reduced the incidence of opportunistic infections, deaths, hospitalizations, HIV-associated cancers, and can potentially achieve near-normal life expectancy.
• HAART involves simultaneous treatment with three or more antiretroviral drugs.

About

• HIV-1: The worldwide predominant cause of HIV infection.
• HIV-2: Less efficiently transmitted, lower levels of viraemia and transmission, and is resistant to NNRTIs. More common in West Africa.

Structure

• HIV is a single-stranded, positive-sense RNA lentivirus.
• It has a dense cylindrical core surrounded by a lipid envelope. The virus binds to host cells through this envelope.
• Contains RNA-dependent DNA polymerase (reverse transcriptase), making it a retrovirus.
• Can form a dsDNA molecule that integrates into the host genome.
• gp120: Essential for viral entry into cells by attaching to cell surface receptors (CD4 and co-receptors).
• gp41: A subunit that helps the virus fuse with host cells.
• p17: A viral core protein (matrix). The viral core is bullet-shaped and contains essential enzymes for replication: reverse transcriptase, integrase, and protease.
• p24: A component of the HIV capsid.
• Protease: Cleaves newly synthesized polyproteins to form mature viral proteins.
• Integrase: Enables integration of viral DNA into the host cell genome.
• RNA: Retroviruses store genetic material in RNA instead of DNA.

Viral Cycle

• Viral gp120 binds with high affinity to the CD4 receptor on host cells.
• Further binding occurs with chemokine receptors (CCR5 and CXCR4).
• Virus fuses and enters the host cell.
• Reverse transcriptase synthesizes dsDNA from the viral RNA genome.
• The dsDNA integrates into the host genome via integrase.
• Host cell machinery produces viral mRNA and proteins.
• New virions are assembled and released.

Genes

• gag: Codes for core structural proteins of the virus.
• pol: Codes for protease, reverse transcriptase, and integrase.
• env: Codes for the envelope glycoproteins (gp120 and gp41).
• vif: Required for producing infectious virions.
• vpr: Codes for a transport protein.
• vpu: Codes for a protein involved in viral assembly.
• tat, rev: Regulatory proteins involved in viral replication.

HIV Tropism

• HIV primarily infects cells with the CD4 surface receptor:
• CD4+ T-helper cells
• B cells, Macrophages, Microglial cells in CNS, Dendritic cells
• Gradual destruction of these cells leads to immunodeficiency.

Transmission

• Historically, via blood transfusions or blood products.
• Sharing needles/syringes for drug use.
• Sexual contact (oral, vaginal, anal) with an HIV-positive individual.
• Risk increases with other STIs like syphilis, herpes, and gonorrhea.
• Vertical transmission: From mother to baby during pregnancy, birth, or breastfeeding.
• Risk depends on the concentration of HIV in the fluid, the quantity introduced, and access to T4 cells.

Epidemiology

• HIV is widespread, affecting millions globally, predominantly in sub-Saharan Africa, China, India, and the Western world.
• Virus transmitted by blood, semen, vaginal fluid, and breast milk.
• High mutation rate complicates treatment.
• Death often due to infections or malignancies in immunocompromised patients.
• HIV-1 is global; HIV-2 is less common and mainly in West Africa, typically less severe.
• HAART changed HIV from fatal to a chronic manageable disease.
• There is a window period post-infection (2-6 weeks) when patients may be antibody-negative but highly infectious.

Possible Early Clues for Testing

• Herpes zoster, B-cell lymphoma
• Paul-Bunnell negative glandular fever-like illness
• Necrotizing gingivitis, Dementia
• Active Tuberculosis
• Recurrent pneumococcal pneumonia

AIDS-Defining Conditions (Infections)

• Bacterial:
  • Mycobacterium avium complex (MAC)/Mycobacterium kansasii
  • Recurrent pneumonia
  • Recurrent Salmonella septicemia
  • Mycobacterium tuberculosis (extrapulmonary or pulmonary)
• Fungal:
  • Candidiasis (bronchi, trachea, lungs, esophagus)
  • Coccidioidomycosis (disseminated or extrapulmonary)
  • Cryptococcosis (extrapulmonary)
  • Histoplasmosis (disseminated or extrapulmonary)
  • Pneumocystis jirovecii pneumonia (PCP)
• Parasitic:
  • Cryptosporidiosis (chronic >1 month)
  • Isosporiasis (chronic >1 month)
  • Toxoplasmosis of the brain
• Viral:
  • Cytomegalovirus (CMV) disease (other than liver, spleen, lymph nodes)
  • CMV retinitis (with vision loss)
  • Herpes simplex virus (HSV) causing chronic ulcers >1 month, or bronchitis, pneumonitis, or esophagitis
  • Progressive multifocal leukoencephalopathy (PML)

AIDS-Defining Conditions (Cancers)

• Kaposi's Sarcoma
• Invasive Cervical Cancer
• Non-Hodgkin Lymphoma: Primary CNS lymphoma, Burkitt's lymphoma, Immunoblastic lymphoma

AIDS-Defining Conditions (Other)

• HIV-related Encephalopathy
• HIV Wasting Syndrome
• Lymphoid Interstitial Pneumonitis (in children <13 years)
• Recurrent Bacterial Infections (in children <13 years)

Clinical Categories

• Category A (HIV Seroconversion Illness):
  • Mild viral illness or severe glandular fever-like illness weeks after infection.
  • Rash, aseptic meningitis. Suspect in patients with risk factors. Take a sexual history.
  • May be followed by persistent generalized lymphadenopathy (PGL), nodes >1 cm in >2 extra-inguinal sites for >3 months without another cause.
• Category B (Signs Suggestive of HIV Infection):
  • Persisting vaginal candidiasis
  • Hairy leukoplakia of the mouth
  • Herpes zoster involving more than a single dermatome
  • Idiopathic thrombocytopenia
  • Pelvic inflammatory disease (PID)
• Category C (Significant Immunosuppression):
  • Indicates significant immunosuppression. CD4 count correlates with susceptibility to various infections.
  • CMV and MAC infections often occur when CD4 <100 cells/µL.

General Manifestations

• General: Anorexia, Wasting syndrome, Fever
• Hepatic: HIV accelerates Hepatitis B and C, leading to potential end-stage liver disease.
• Cardiology: Myocarditis, Cardiomyopathy may occur. Echocardiography is useful.
• Haematology: Anaemia, Thrombocytopenia (autoimmune)
• Gastrointestinal: HIV enteropathy with diarrhea and weight loss, Cryptosporidiosis causes chronic diarrhea
• Renal: Nephrotic syndrome and HIV-associated nephropathy (HIVAN)
• Endocrine: Adrenal insufficiency (uncommon)

  

  

  CNS PML:

  
  • Neurological:
    • Cerebral toxoplasmosis (multiple ring-enhancing lesions), treat with pyrimethamine + sulfadiazine.
    • Cryptococcal meningitis: Yeast identified by India ink stain, cryptococcal antigen tests.
    • CNS lymphoma: Associated with EBV, may appear as single or multiple lesions.
    • Progressive multifocal leukoencephalopathy (PML): White matter disease due to JC virus.
    • Neurosyphilis, HIV dementia, encephalopathy, neuropathies.
  
  • Dermatological:
    • Seborrheic dermatitis, Kaposi's sarcoma
    • Zoster infection, Increased melanoma
    • Molluscum contagiosum on the face
    • Stevens-Johnson syndrome due to antiretrovirals
    • Anal and nail fold squamous cell carcinoma
  • Ophthalmic:
    • Cotton wool spots on fundoscopy
    • CMV retinitis (CD4<50), treatable, can cause visual loss
    • Toxoplasmic chorioretinitis

  Information

  • Pre-test counselling is recommended, discussing risks and implications of a positive result.
  • Initial test is usually an ELISA. If positive, confirm with different immunoassays or Western Blot.

  Poor Prognosis Indicators

  • Anaemia
  • Low platelets
  • Raised Beta₂-microglobulin
  • High HIV RNA viral load
  • Low CD4+ count (<200 cells/mm³)

  Investigations

  • CD4 count is the most important test in assessing HIV progression. Normal >500 cells/mm³.
  • CD4 count = (total lymphocytes) × (%CD4+ on flow cytometry)
  • Repeat every 3-4 months along with viral load.
  • AIDS is defined as CD4 <200 cells/mm³.
  • Advanced AIDS: CD4 <50 cells/mm³.

  New HIV Patient Check

  • Clinical assessment: mouth (ulcers, thrush), skin (Kaposi's), lymph nodes, weight
  • Check LFTs, U&E, eGFR
  • Fasting glucose, lipids, bone profile, 25(OH)D
  • Urinalysis, urine protein/creatinine ratio

  Immunology

  • Lymphocyte subsets
  • HLA B*5701 status

  Virology

  • HIV Ab, HIV viral load, HIV genotype and subtype
  • HAV IgG, HBsAg, Hep C Ab

  Other Tests

  • Toxoplasmosis serology
  • Syphilis serology
  • STI screen
  • Cervical cytology
  • Chest X-ray
  • Cardiovascular and fracture risk assessment

  Neurology Work-Up

  • FBC, U&E, LFT, TFT, Ammonia
  • Cryptococcal antigen
  • CMV DNA PCR
  • RPR, FTA-ABS (Syphilis)
  • Toxicology, B12
  • CD4 count, HIV viral load

  CSF Studies

  • Cell count, differential, Gram stain, protein, glucose
  • Cryptococcal antigen
  • EBV, CMV, VZV, HSV DNA PCR
  • JC virus DNA PCR
  • Bacterial, TB, fungal cultures

  Imaging

  • MRI with gadolinium

  Management and AIDS HAART Antiretrovirals