10.04 HIV/AIDS

1. Overview & Causative Agent

Human Immunodeficiency Virus (HIV):

• Type: Retrovirus
• Target: Immune system, specifically T-helper (CD4⁺) lymphocytes.
• Impact: Leads to Acquired Immunodeficiency Syndrome (AIDS) if untreated.

Retrovirus Characteristics:

• Genetic Material: Single-stranded RNA.
• Replication Mechanism: Utilizes reverse transcriptase to convert RNA into DNA within host cells.
• Integration: Viral DNA integrates into the host genome, facilitating persistent infection and replication.

Acquired Immunodeficiency Syndrome (AIDS):

• Definition: Advanced stage of HIV infection.
• Characteristics: Severe immune system compromise, increased vulnerability to opportunistic infections and certain cancers.
• Diagnosis: Clinical criteria include low CD4⁺ T-cell counts and the presence of specific opportunistic infections or cancers.

Global Impact (2017 Estimates):

• People Living with HIV: 36.9 million globally.
  • Regional Prevalence: 67% reside in sub-Saharan Africa.
• New Infections: 1.8 million annually.
• AIDS-related Deaths: 940,000 annually.

2. Virus Structure

Components of HIV:

• Envelope:
  • Composition: Lipid membrane derived from the host cell.
  • Glycoproteins: gp120 (binds to CD4 receptors) and gp41 (facilitates fusion with host cell membrane).
• Capsid:
  • Protein Core: Contains two copies of RNA genome.
  • Enzymes:
    • Reverse Transcriptase: Converts RNA to DNA.
    • Protease: Processes viral polyproteins.
    • Integrase: Integrates viral DNA into host genome.

3. Transmission of HIV

Primary Transmission Routes:

1. Sexual Contact:
   • Transmission via semen, vaginal fluids, and rectal fluids.
2. Blood Transfusions:
   • Risk from contaminated blood or blood products (significantly reduced with screening).
3. Needle Sharing:
   • Common among intravenous drug users.
4. Vertical Transmission:
   • From mother to child during pregnancy, childbirth, or breastfeeding.

High-Risk Groups:

• Individuals with multiple sexual partners.
• Intravenous drug users sharing needles.
• Hemophiliacs (prior to routine blood screening).
• Infants born to HIV-positive mothers.

Unique Transmission Characteristics:

• No Vector: Unlike vector-borne diseases, HIV is not transmitted by insects or animals.
• Fragility Outside Host: HIV cannot survive long outside the human body; transmission requires direct fluid exchange.

4. Infection Process and Immune Impact

Target Cells:

• CD4⁺ T-helper Lymphocytes: Central to orchestrating the immune response; depletion leads to immune dysfunction.
• Macrophages: Serve as reservoirs for the virus and contribute to dissemination.
• Microglial Cells (Brain): Infection can lead to neurological complications.

Pathogenesis:

1. Entry: gp120 binds to CD4 and a co-receptor (CCR5 or CXCR4) on host cells.
2. Fusion: gp41 facilitates fusion of viral and cellular membranes.
3. Reverse Transcription: Viral RNA is reverse-transcribed into DNA.
4. Integration: Viral DNA integrates into the host genome via integrase.
5. Replication: Host machinery transcribes viral genes, leading to production of new virions.
6. Assembly and Release: New viruses bud from the host cell, acquiring an envelope.

Immune System Impact:

• CD4⁺ T-cell Depletion: Impairs adaptive immunity, weakening responses to pathogens.
• Chronic Immune Activation: Leads to immune exhaustion and further CD4⁺ T-cell loss.

Opportunistic Infections in AIDS:

• Fungal Infections:
  • Candida albicans (Oral thrush)
  • Pneumocystis jiroveci (Pneumonia)
• Cancers:
  • Kaposi’s sarcoma (associated with Human Herpesvirus 8)
• Other Infections:
  • Mycobacterium tuberculosis (Tuberculosis)
  • Various bacterial and viral infections
  • Neurocognitive disorders (e.g., HIV-associated dementia)

5. Clinical Features

6. Impact on Society and Economy

Health and Economic Strain:

• Sub-Saharan Africa: Disproportionate burden affecting economically active populations (ages 20-39).
• Healthcare Systems: Overwhelmed by the dual burden of HIV/AIDS and opportunistic infections.

Economic Consequences:

• Workforce Productivity: Loss of skilled labor reduces economic output.
• Healthcare Costs: Increased spending on treatment and management of HIV/AIDS.
• Long-Term Growth: Some regions experience reversed economic growth trends due to the epidemic.

Social Impact:

• Stigma and Discrimination: Affects individuals’ mental health and access to services.
• Orphaned Children: Increased number of children losing parents to AIDS, impacting education and social structures.

7. Treatment of HIV/AIDS

Antiretroviral Therapy (ART):

• Objective: Suppress viral replication, restore immune function, prevent progression to AIDS.
• Mechanism: Targets various stages of the HIV life cycle to inhibit viral replication.

Common ART Classes and Drugs:

1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs):
   • Zidovudine (AZT): Mimics thymidine, inhibits reverse transcriptase.
2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs):
   • Bind reverse transcriptase at a different site, causing conformational changes.
3. Protease Inhibitors (PIs):
   • Inhibit viral protease, preventing maturation of viral proteins.
4. Integrase Strand Transfer Inhibitors (INSTIs):
   • Block integration of viral DNA into host genome.
5. Entry Inhibitors:
   • Prevent viral entry into host cells (e.g., fusion inhibitors like enfuvirtide).

Combination Therapy (HAART):

• Highly Active Antiretroviral Therapy (HAART): Combination of at least three antiretroviral drugs from at least two different classes.
• Benefits: Enhances efficacy, reduces risk of resistance, improves immune function.

Challenges in Treatment:

• Side Effects: Range from mild (nausea, rash) to severe (lipodystrophy, neuropathy).
• Adherence: Strict dosing schedules are essential to prevent development of drug-resistant strains.
• Access: Limited availability in low-income regions hampers treatment efforts.

Progress and Outcomes:

• Mortality Reduction: ART has led to a 48% decline in AIDS-related deaths between 2005 and 2016.
• Life Expectancy: With effective ART, individuals can maintain near-normal life expectancy.

8. Prevention of HIV/AIDS

Behavioral Interventions:

• Education Programs: Increase awareness about transmission, safe sex practices, and reducing stigma.
• Condom Distribution: Promote consistent and correct use to prevent sexual transmission.
• Needle Exchange Programs: Provide sterile needles to reduce transmission among intravenous drug users.

Barriers to Sexual Transmission:

• Barrier Methods:
  • Male Condoms: Effective in preventing fluid exchange.
  • Female Condoms (Femidoms): Alternative for women.
  • Dental Dams: Used during oral sex to prevent exposure to fluids.

Prevention of Mother-to-Child Transmission:

• ART for Pregnant Women: Significantly reduces the risk of transmission during pregnancy, delivery, and breastfeeding.
• Delivery Methods: Elective cesarean section may be recommended in certain cases.
• Breastfeeding Guidelines:
  • High-Income Countries: Generally advised against breastfeeding by HIV-positive mothers.
  • Low-Income Countries: May recommend breastfeeding if ART is accessible, to prevent other infections.

Contact Tracing & Testing:

• Partner Notification: Identifying and testing sexual or needle-sharing partners of HIV-positive individuals.
• Public Testing Initiatives: Encourage regular screening among high-risk populations (e.g., men who have sex with men, sex workers, drug users).

Blood Safety:

• Screening: Rigorous testing of blood and blood products for HIV.
• Inactivation Techniques: Treat blood to inactivate any potential viral contaminants.
• Personal Donations: Encourage voluntary, non-remunerated blood donations to ensure safety.

9. Global Challenges in HIV Prevention

Long Latency Period:

• Asymptomatic Phase: Individuals can transmit HIV for years without showing symptoms, complicating efforts to identify and treat infections early.

Vaccine Development:

• HIV’s High Mutation Rate: Allows the virus to evade immune responses and develop resistance, making vaccine design challenging.
• Genetic Diversity: Extensive variability among HIV strains hinders the creation of a broadly effective vaccine.

Public Health Strategies:

• Varied Testing Approaches: Differences in healthcare infrastructure and cultural attitudes affect testing strategies across countries.
• Targeted vs. Widespread Testing: Developed regions often target high-risk groups, whereas low-income areas may struggle with implementing widespread testing programs.

10. Recent Advances

Home Testing Kits:

• Advantages: Provide privacy, reduce stigma, and facilitate early detection.
• Accessibility: Increased availability contributes to higher testing rates, especially in resource-limited settings.

Reduction in Pediatric AIDS:

• ART for Pregnant Women: Dramatically decreases the rate of mother-to-child transmission.
• Preventive Measures: Combination of ART, safe delivery practices, and appropriate infant feeding strategies.

International Efforts:

• Education Campaigns: Global initiatives to raise awareness and reduce transmission.
• ART Scale-Up: Expanding access to antiretroviral therapy in low- and middle-income countries, leading to declines in new infections and AIDS-related deaths.

11. Data Analysis and Interpretation

Data on HIV from 2000 to 2017:

• a. i. Calculate Percentage Change:
  • Given: People living with HIV increased from 28.9 million (2000) to 36.9 million (2017).
  • Calculation:

• Interpretation: There was a 27.68% increase in the number of people living with HIV from 2000 to 2017.
• a. ii. “Living with HIV” Meaning:
  • Definition: Individuals who are HIV-positive, regardless of symptom presentation. This includes those who are asymptomatic or receiving treatment to manage the infection.
• b. i. Data Summary:
  • Trend: Steady increase in the number of HIV cases over the years, accompanied by a significant rise in the number of individuals receiving antiretroviral treatment.
• b. ii. Why Data Are Estimates:
  • Reasons:
    • Underreporting due to stigma or lack of access to testing.
    • Limited testing infrastructure in certain regions.
    • Variability in data collection methods across countries.

Advice for HIV/AIDS Education Programs:

• Promote Safe Sex Practices: Emphasize the consistent use of condoms and other barrier methods.
• Educate on Risks of Needle Sharing: Highlight the dangers of sharing needles and promote harm reduction strategies.
• Encourage Regular Testing: Advocate for routine HIV screening, especially among high-risk populations.
• Inform About ART Availability: Raise awareness about treatment options and their benefits in managing HIV.

Risk of HIV Infection in Children Receiving Transfusions:

• Risk Factors:
  • Transmission through contaminated blood products if not properly screened.
  • Importance of rigorous blood screening protocols to ensure safety.

Importance of Early HIV Detection:

Benefits:

• Timely Treatment Initiation: Allows for earlier commencement of ART, improving health outcomes.
• Reduced Transmission Risk: Early detection facilitates behavioral changes and treatment that lower the likelihood of spreading the virus.
• Prevention of Immune System Damage: Preserves immune function by controlling viral replication before significant CD4⁺ T-cell loss.
• Improved Quality of Life: Individuals can maintain better health and productivity with early intervention.

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