Human Immunodeficiency Virus

HIV is a single stranded RNA retrovirus that infects and replicates within the human immune system using host CD4 cells

Aetiology

Causative organism

  • HIV is an RNA retrovirus
  • HIV-1 group M responsible for global epidemic
  • MSM is the risk group for the majority of prevalent infections and new infections in the UK

Transmission

  • Sexual transmission accounts for 79% of the new infections in the UK
    • Factors increasing transmission risk: anoreceptive, trauma, genital ulceration, concurrent STI
  • Parental transmission
    • Injection drug use
    • Infected blood products
    • Iatrogenic
  • Mother-to-child
    • In utero/trans-placental
    • Delivery
    • Breastfeeding

Pathophysiology

Infection

  • Infection of mucosal CD4+ cell
  • Transport to regional lymph nodes
  • Infection established within 3 days of entry
  • Dissemination of virus

Immunopathogenesis

  • CD4+ receptors are the target site for HIV
    • CD4 is a glycoprotein found on the surface of a range of cells, including T helper lymphocytes (CD4+ cells), dendritic cells, macrophages and microglial cells
  • CD4+ Th lymphocytes are essential for induction of adaptive immune response
    • Recognition of MHC2 antigen-presenting cell
    • Activation of B-cells
    • Activation of cytotoxic T cells (CD8+)
    • Cytokine release
  • Effect of HIV infection on the immune response:
    • Reduced circulating CD4+ cells
    • Reduced proliferation of CD4+ cells
    • Reduction in CD8+ T cell activation
      • Dysregulated expression of cytokines
    • Reduction in antibody class switching
      • Reduced affinity of antibodies produced
    • Chronic immune activation
  • This will increase susceptilibity to viral infections, fungal infections, mycobacterial infections, and infection-induced cancers

Clinical presentation

Primary HIV infection

  • Up to 80% present with symptoms
  • Onset average 2-4 weeks after infection
  • Symptoms:
    • Fever
    • Rash (maculopapular)
    • Myalgia
    • Pharyngitis
    • Headache/aspetic meningitis
  • Very high risk of transmission at this stage

Asymptomatic HIV infection

  • Ongiong viral replication, CD4 count depletion and immune activation
  • Risk of onward transmission if remains undiagnosed

AIDS-defining conditions

Opportunistic infection
  • Infection by an individual that does not normally produce disease in a healthy individual
  • Pneumocystis pneumonia (PCP) - CD4+ <200
    • Symptoms: insidious onset SOB and dry cough
    • Signs: exercise oxygen desaturation
    • CXR: may be normal, interstitial infiltrates, reticulonodular markings
    • Diagnosis: BAL and immunofluorescence +/- PCR
    • Management: high dose co-trimoxazole
    • Prophlaxis in patients CD4+ <200: low dose co-trimoxazole (also offers some protection against cerebral toxoplasmosis)
  • Tuberculosis - more likely to have symptomatic primary infection, reactivation of latent TB, miliary TB, extrapulmonary TB
  • Cerebral toxoplasmosis - CD4+ <150
    • Caused by toxoplasma gondii
    • Reactivation of latent infection - multiple cerebral abscess, chorioretinitis
    • Presentation: headache, fever, focal neurology, seizures, reduced consciousness, raised ICP
  • Cytomegalovirus - CD4+ <50
    • Reactivation of latent infection - retinitis, colitis, oesophagitis
    • Presentation: reduced visual acuity, floaters, abdominal pain, diarrhoea, PR bleeding
    • Opthalmic screening for all individuals CD4+ <50
  • HIV-associated neurocognitive impairment
    • HIV-1
    • Reduced short term memory +/- motor dysfunction
  • Progressive multifocal leukoencephalopathy
    • JC virus (reactivation)
    • CD4 <100
    • Presentation: rapidly progressing, focal neurology, confusion, personality change
  • Skin infections
    • Herpes zoster - multidermatomal, recurrent
    • Herpes simplex - extensive, hypertrophic, aciclovir resistant
    • HPV - extensive, recalcitrant, dysplastic
HIV-associated wasting
  • 'Slim's disease'
  • Multiple aetiologies - metabolic, anorexia, malabsorption/diarrhoea, hypogonadism
AIDS-related cancers
  • Increased incidence with increased immunosupression
  • Kaposi's sarcoma
    • Vascular tumour caused by HHV8
    • Clinical presentation: cutaneous, mucosal, visceral (pulmonary, GI)
    • Management: anti-retrovirals, local therapies, systemic chemotherapy
  • Non-Hodgkin's lymphoma
    • EBV
    • Clinical presentation: more advanced, B symptoms, bone marrow involvement, extranodal disease, increased CNS involvement
    • Investigations: as for HIV negative
    • Management: as for HIV negative, add antiretrovirals
  • Cervical cancer
    • HPV - persistence of HPV infection, rapid progression to dysplasias and invasive disease
    • HIV testing should be offered to all patients with complicated HPV disease

Non-AIDs symptomatic HIV

  • Mucosal candidiasis
  • Seborrhoeic dermatitis
  • Diarrhoea
  • Fatigue
  • Worsening psoriasis
  • Lymphadeopathy
  • Parotitis
  • Epidemiologically linked conditions - STIs, hep. B, hep. C

Neurological presentations

  • Distal sensory polyneuropathy
  • Mononeuritis multiplex
  • Vacuolar myelopathy
  • Aspectic meningitis
  • Guillan-Barre syndrome
  • Viral meningitis (CMV, HSV)
  • Cryptococcal meningitis
  • Neurosyphilis

Haematologic manifestations

  • Caused by: HIV, opportunistic infections (MAI), AIDS-malignancies (lymphomas)
  • Leuko/lymphopenias (due to decreased CD4)
  • Thrombocytopenia (HIV affects megakaryocytes)

Investigations

  • HIV antibody testing should be routinely offered where there is a clinical indicator disease (regardless of perceived risk)
  • An HIV test may be falsely negative in the first 45 days (if 4th generation test used) following infection

Management

HAART

  • Highly active antiretroviral therapy (HAART) - does not cure HIV, but aims to reduce the viral load to undetectable levels in the serum
  • A number of classes of drugs including nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs) are used in combination to target the enzymes used in viral replication and maturation
  • Where possible, these drugs are combined into one tablet to be taken daily e.g. atripla, stribild, eviplera

Prevention of transmission

  • Pre-exposure prophylaxis (PrEP)
  • After 72 hours of high risk exposure - post-exposure prophylaxis (PEP)
  • Prevention of mother to child transmission:
    • HAART during pregnancy
    • Vaginal delivery if undetected viral load
    • Caesarean section if detected viral load
    • 2-4/52 PEP for neonate
    • Exclusive formula feeding