HIV And AIDS

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HIV And AIDS

• World-wide estimation 30-40 million people infected by 2000
• Following inoculation of a naïve host with biological fluid (blood, blood products or sexual secretions) containing HIV-1, the virus adheres to cells expressing CD4 and its coreceptor CCR5 and enters cell
• HIV produces its own DNA from RNA which is incorporated into host DNA and replicated
• This process allows several therapeutic targets
  • Entry of virus into cell via CD4/CCR5 receptor combination
  • HIV-DNA polymerase (reverse transcriptase)
  • The integrase enzyme
  • The transactivator of transcription (tat) protein that accelerates replication viral RNA
  • HIV-1 protease
• Newly formed HIV-1 Virons infect CD4/CCR5-+ cells and subsequently impair host immune response by killing/inhibiting CD4/CCR5-+ cells therefore individual at high risk of opportunistic infection

Aetiology

• HIV infection →
  • progressive fall in CD4 T-helper cell
  • failure of T-cell proliferation after stimulation
• AIDS

AIDS Definition

• progressive immunodeficiency without another cause manifested by
  • opportunistic infections
    • CMV
    • M. Tuberculosis
    • Candida Albicans
    • Pneumocystis carinii
  • Tumours
    • Kaposi's sarcoma
    • Non T-Cell lymphoma
  • Neurological manifestations
    • progressive multifocal leukoencephalopathy

Epidemiology

• estimated 30-40 million HIV infected worldwide

Transmission

• (N. America, Western Europe, UK)
  • IV drug users
  • Homosexual activity
• (Sub-saharan africa, Asia)
  • heterosexual activity
  • infected blood products

HIV life-cycle

• CD4 / CCR5 expressing cells invaded
• HIV produces DNA from RNA (reverse transcriptase)
• DNA incorporated into host genome and replicate
• 10.3 x 10⁹virions produced each day
• mean time for generation 2.6 days

Symptoms and Signs

• seroconversion illness
  • meningism
  • skin rash
  • temperature
  • lymphadenopathy
• Pre-AIDS
  • Buccal Candidiasis
  • Oral hairy leukoplakia
  • marked asthenia / weakness
• AIDS
  • opportunistic infections

Complications

• Eyes

Investigations

• HIV serology
  • Antibody positive within 3 months of infection
• CD4 count
  • normal 800x10⁶ / L
  • if <200 then risk of opportunistic infections
• HIV p24 antigen
  • implies active replication
  • poor prognosis

Treatment

Aim

• Maximal suppression of HIV replication for as long as possible

Recommended guidelines

• Treat before significant immunosuppression occurs
• Treament criteria
  • HIV RNA copies if 5000-10 000/ml or more
  • or CD4 count <500
  • or symptoms
• Combination therapy used
• Standard care
  • 2 nucleoside analogue RT inhibitors + protease inhibitor
  • 2 NRTIs + 1 NNRTI
• Treatment failure/resistance change 2 or all 3 drugs

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