Lecture 7.2 - Blood borne viruses - Human Immunodeficiency Virus (HIV)

HIV Diagnosis and Testing

• Appear at 3-12 weeks and persist for life
• Current tests detect both Ag and Ab, with results available on the same day, but may yield false negative results
• Blood tests (PCR) detect HIV nucleic acid, are highly sensitive, and detect very early infection (few days), used for follow-up/treatment response
• "Rapid" tests are low-cost, take < 1 hour, and detect HIV antibody, with options for blood (finger-prick), oral (saliva), in-home, and postal testing

Who Should be Tested?

• Patients presenting with:
  • Respiratory: bacterial pneumonia/TB
  • Neurology: meningitis/dementia
  • Dermatology: severe psoriasis, recurrent/multi-dermal shingles
  • Gastroenterology: Chronic diarrhoea/weight loss
  • Haematology: any unexplained blood abnormality
  • Oncology: lymphoma, anal cancer
  • Gynaecology: cervical intraepithelial neoplasia (CIN)
  • Sexually transmitted diseases: Hep B/Hep C

HIV Therapy

• Aims:
  • Undetectable HIV viral load
  • Reconstitute CD4 count/immune system
  • Reduce risk of transmission
  • Good quality of life (low side effects, compliance)
  • Normalise lifespan
• Targets:
  • Post-attachment inhibitors
  • Fusion inhibitors
  • Reverse transcriptase inhibitors
  • Integrase inhibitors
  • Protease inhibitors

Why Give 3 or More ART?

• Millions of rounds of viral replication each day
• Virus mutates (changes/adapts) every 2-3 rounds
• Resistance to drugs can develop in days
• 1 drug - resistance develops quickly
• 3 drugs - harder to develop resistance
• Patient must keep taking drugs

Considerations for Exposure to HIV

• Emergency anti-HIV medicine called post-exposure prophylaxis (PAP) may stop individuals becoming infected if started within 72 hours of possible exposure
• An early diagnosis means treatment can start sooner, improving the chances of controlling the virus, reducing the risk of becoming unwell, and reducing the chance of passing the virus on to others
• Both positive and negative HIV tests may need to be repeated 1 to 3 months after potential exposure to HIV infection (window period)

Strategies for Prevention of HIV

• Education (understanding of spread/control, reduce stigma)
• Increase condom usage
• Prevention of mother-to-child transmission (testing)
• Increase testing
• Needle and syringe programme (IV drug users)
• Male circumcision
• Post-exposure prophylaxis (PEP)
• Pre-exposure prophylaxis (PrEP) for people at high risk of HIV infection
• Development of vaccine(s)

The Good News

• Decline in new diagnoses in homosexual men
• Decline in new diagnoses in Black African heterosexuals in the UK
• Decline in new HIV diagnoses, AIDS, and deaths
• Reduction in time to start treatment

Future Therapies

• Use of haematopoietic stem cell transplantation (HSCT) with absence of surface expression of the CCR5

Ethical Dilemmas in HIV

• Psychological impact of diagnosis
• Dealing with stigma
• Patient confidentiality vs. health of mother, unborn child, sexual contact, older child, and patients/staff at workplace

Global Distribution of HIV

• The vast majority of people with HIV are in low and middle-income countries
• In 2022, there were 25.6 million people with HIV in the African region, 3.8 million in the Americas, 3.9 million in the South East Asian region, and 3.0 million in the European region

Prevalence of HIV in the UK

• An estimated 102,168 people were living with HIV in the UK in 2022, including undiagnosed cases
• Breakdown by transmission route:
  • Homosexual men: 46.9%
  • Heterosexuals: 48.6%
  • IV drug use: 1.8%
  • Vertical transmission: 1.8%

Human Immunodeficiency Virus (HIV)

• Human immunodeficiency virus (HIV-1 and HIV-2)
• Has its own reverse transcriptase to convert RNA into DNA
• Retrovirus ("backwards") with ssRNA, DNA, ssRNA
• Infects cells with CD4
• Surface receptor: T-helper lymphocytes, monocytes/macrophages
• HIV replicates inside cells, spreading to/infecting more cells

Replication of HIV

• HIV replicates inside cells, spreading to/infecting more cells

Transmission

• Contact of infected bodily fluids with mucosal tissue/blood:
  • Unprotected sexual intercourse (anal/vaginal)
  • IV drug users (sharing needles)
• Medical procedures:
  • Blood/blood-products transfusion
  • Surgery
  • Needlestick injury
  • Skin grafts, organ transplant
• Vertical transmission:
  • Mother to baby (during pregnancy, at the time of birth, breast milk)

Factors Affecting HIV Transmission

• Type of exposure:
  • Type of sexual act (use of condoms)
  • Transfusion, needlestick, mucous membrane
  • Other STI (inflammation of genital tract)
  • Sexual assault
• Viral level (viral load) in blood:
  • U=U -> sustained undetectable viral load (VL) for 6/12 means that HIV is untransmittable

Living with HIV in the UK

• Life expectancy and quality of life now excellent with:
  • Early detection and treatment
  • Adherence to treatment
  • Healthy living (avoiding smoking, alcohol, and metabolic problems)
• Late detection = worse prognosis (x10 risk of death in 1st year)
• 66% of over 65-year-olds detected late