HIV

Integration of Proviral DNA into Human DNA
  • The process of HIV infection involves the integration of proviral DNA into human DNA using the enzyme integrase.
  • Upon integration, the proviral DNA resides within the host genome, often termed a "latent reservoir."
  • Replication involves:
    • Reverse transcription of the viral RNA into DNA using reverse transcriptase.
    • Transcription of the integrated DNA back into genomic RNA and messenger RNA (mRNA) by the host's own machinery.
    • Protease enzyme then cleaves long polyprotein chains into functional individual proteins to assemble new virions.
Role of Reverse Transcriptase Enzyme
  • Reverse transcriptase inhibitors are classified into two main types:
    • Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs): These act as false building blocks to stall DNA chain synthesis.
    • Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): These bind directly to the enzyme to inhibit its activity.
  • Combination therapy, often called Antiretroviral Therapy (ART), is essential to prevent the emergence of drug-resistant viral strains.
Impact on Immune System and CD4 Cells
  • HIV targets cells expressing the CD4 receptor, primarily T-helper lymphocytes, but also uses co-receptors like CCR5 or CXCR4 for entry.
  • Infection of a CD4+ cell is problematic because:
    • It turns the body's primary defense coordination cell into a virus factory.
    • As the infection progresses, the absolute number of CD4 cells drops, eventually leading to profound immunodeficiency.
    • Lymphocyte functionality declines; they lose the ability to respond to common pathogens, increasing susceptibility to opportunistic infections.
Structure of HIV Virus
  • The virus is an enveloped retrovirus:
    • Outer Envelope: Contains glycoproteins gp120 (for attachment) and gp41 (for fusion/entry).
    • Capsid: A cone-shaped core containing the p24 protein.
  • For diagnostic purposes:
    • Antigen-antibody (4th generation) tests are standard, detecting the p24 capsid antigen (which appears early) and antibodies to HIV-1/HIV-2.
Characteristics of HIV-1 vs. HIV-2
  • HIV-1: The most common cause of AIDS globally. It has high virulence and progresses rapidly.
    • Viral load can jump to 3,000−10,0003,000 - 10,000 copies within weeks of initial infection (the acute phase).
  • HIV-2: Found primarily in West Africa; it is less transmissible and progresses much slower than HIV-1.
  • Monitoring involves tracking the CD4 count (expressed as cells/$\mu L$) and the viral load (copies/mL).
Treatment Considerations
  • Resistance testing is performed before starting treatment to identify mutations that might render certain drugs, like NNRTIs, ineffective.
  • Transmission Risk: Directly proportional to viral load. The concept of "Undetectable = Untransmittable" (U=UU=U) means that a person with an undetectable viral load has effectively no risk of sexually transmitting the virus.
  • Ulcerative lesions (e.g., from Syphilis or Herpes) increase risk because they provide a direct portal of entry or exit for the virus.
Modes of Transmission
  • Transmission routes:
    • Unprotected sexual contact (highest risk in receptive anal intercourse).
    • Blood-to-blood contact (e.g., shared needles).
    • Vertical transmission (mother-to-child during pregnancy, birth, or breastfeeding).
  • Risk quantification:
    • Needle stick injury risk is approximately 0.3%0.3\% (or 1 in 333).
    • Saliva, tears, and sweat typically do not contain enough virus for transmission unless contaminated with visible blood.
Diagnosis and Testing
  • Qualitative tests: Used to screen for the presence of the virus (Yes/No).
  • Quantitative tests: Used for management to measure the number of viral copies. A "blip" is a small, temporary rise in viral load, whereas a sustained rise may indicate treatment failure.
  • Window Period: There is a delay between infection and when a test can detect the virus; 4th generation tests shorten this to roughly 18−4518 - 45 days.
Stages of HIV Infection
  1. Acute Infection: High viral load, highly contagious, often accompanied by flu-like symptoms.
  2. Chronic Infection (Clinical Latency): Virus reproduces at low levels. Can last 10+10+ years without treatment.
  3. AIDS: Defined as a CD4 count below 200200 cells/$\mu L$ or the presence of specific opportunistic infections (e.g., Kaposi's sarcoma, PCP pneumonia).
Patient Compliance and Prophylaxis
  • HLA-B*5701 Testing: Mandatory before prescribing Abacavir to prevent a potentially fatal hypersensitivity reaction.
  • Pre-Exposure Prophylaxis (PrEP): For HIV-negative individuals at high risk.
  • Post-Exposure Prophylaxis (PEP): Must be started within 7272 hours of a potential exposure and continued for 28 days.