HIV Infection Risks and Transmission

HIV: Risk Factors

• Unprotected sexual intercourse, especially receptive anal intercourse, increases the risk of HIV transmission.
• Sharing of intravenous drug paraphernalia, such as needles, can spread HIV.
• Multiple sexual partners increases the probability of contracting HIV.
• Individuals with sexually transmitted diseases (STDs), including gonorrhea, chlamydia infection, syphilis, and herpes genitalis, are at higher risk of HIV infection.
• Mucosal contact with infected blood or sharp injuries can lead to HIV transmission.

HIV: Transmission

• The primary modes of HIV transmission are sexual contact, including oral, anal, and vaginal intercourse.
• HIV can be transmitted through blood transfusions or direct contact with infected blood, such as through needle sticks.
• Mothers infected with HIV can transmit the virus to their infants during pregnancy, delivery, or breastfeeding.
• HIV is not transmitted through casual contact, such as touching, hugging, kissing, coughing, sneezing, or sharing glasses, plates, or utensils.

HIV: Immunity

• Once infected with HIV, an individual is considered infected for life due to the integration of viral DNA into the host's DNA.
• HIV evades the host's immune system through several mechanisms:
  • Integration of viral DNA into host cell DNA: This allows HIV to persist within the host's cells.
  • A high rate of mutation of the env gene: This constant genetic variation makes it difficult for the immune system to recognize and target the virus.
  • Antigenic drift of gp120: This protein on the surface of HIV undergoes changes, evading antibodies produced by the immune system.
  • Production of Tat and Nef proteins: These proteins downregulate class 1 MHC proteins, which are essential for cytotoxic T cells to recognize and kill infected cells.
• The main immune response to HIV infection involves cytotoxic CD8-positive lymphocytes, which control the virus for many years.
• When the number of CD4 helper T cells declines, cytotoxic T cells lose their effectiveness, as they rely on lymphokines produced by CD4 T cells.
• Antibodies against HIV proteins, such as p24, gp120, and gp41, are produced, but they are not very effective at neutralizing the virus in the body.

HIV: Pathogenesis

• HIV enters the body and binds to CD4 T cells, which are found on monocytes, macrophages, and dendritic cells.
• HIV subsequently binds to chemokine receptors on host cells, leading to entry and infection.

HIV: Effects

• HIV infects CD4-positive cells, including T cells and macrophages, and kills them, suppressing the immune system.
• This suppression increases the risk of opportunistic infections (OI) and certain cancers, such as Kaposi's sarcoma and lymphoma.
• HIV does not directly cause these cancers; its genes are not found in the cancer cells.
• HIV infection disrupts the normal functioning of the immune system, leading to dysregulation of immune functions and loss of B cell control.
• Effects of HIV Infection:
  • Eye: Cytomegalovirus (CMV) retinitis.
  • Gastrointestinal (GIT): Oral and esophageal candidiasis (thrush), Cryptosporidiosis.
  • Skin: Kaposi's sarcoma, herpes zoster, molluscum-like lesions caused by T. marneffei.
  • Respiratory (RESP): Pneumonia (e.g., caused by Mycobacterium tuberculosis/Mycobacterium avium complex, Streptococcus pneumoniae, CMV, Pneumocystis jirovecii).
  • Central Nervous System (CNS): Herpes simplex virus (HSV) encephalitis, cryptococcal meningitis, toxoplasmosis.
  • Genitourinary (GUI): Cervical cancer.

HIV Infection: Stages

• Primary/Acute Infection: This stage may resemble mononucleosis, with symptoms like fever, rash, and generalized lymphadenopathy. Viral load increases, while CD4 counts decrease.
• Asymptomatic: This stage may last for years, with patients experiencing no symptoms. CD4 counts remain above 400 cells/mm3, although they are reduced from their normal levels.
• Opportunistic Infection (OI)/AIDS: This stage occurs when CD4 counts fall below 200 cells/mm3, indicating severe immunosuppression. Patients may develop one or more opportunistic infections due to the weakened immune system.

HIV Infection: Lab Investigations

• Screening Tests:
  • HIV-1/2 Antigen/Antibody immunoassay/Combo: This test detects both HIV-1 and HIV-2 antibodies and antigens.
• Supplementary/Secondary Tests:
  • Detection of p24/p31 antigen and glycoproteins (gp120/160 and gp41): These tests can detect a greater number of recent infections before seroconversion.
  • Qualitative HIV-1 Nucleic Acid (RNA) test: This test detects HIV-1 RNA, useful for early detection and monitoring viral load.
  • Rapid HIV assay/test (e.g., Alere Determine HIV-1/2 Ag/Ab Combo test): These tests provide rapid results and are approved for use in serum, plasma, and whole blood.
  • Western Blot: This test is highly specific and less likely to produce false-positive results.
  • Indirect fluorescent antibody (IFA) test: This test is highly specific but more expensive than a Western blot.
  • Proviral DNA PCR: This test is usually performed in newborns to distinguish maternal antibodies from actual infection.

HIV Infection: Initial Workup

• When a patient is diagnosed with HIV, a comprehensive initial workup should be performed to assess their overall health and identify potential risks. This workup includes:
  • CMV: An anti-CMV IgG test to determine prior exposure to CMV and the risk of retinitis reactivation.
  • Syphilis: An RPR (rapid plasma reagin) test to assess syphilis status, with confirmatory testing if positive.
  • Gonorrhea and Chlamydial Infection: Rapid amplification testing (RPA) to screen for these infections.
  • Hepatitis A, B, and C: Serology testing to assess the presence of these infections.
  • Toxoplasmosis: An anti-toxoplasma antibody test to determine prior exposure and the risk of toxoplasmosis reactivation.
  • Tuberculosis (TB): A purified protein derivative (PPD) skin test to evaluate for TB infection.
  • Ophthalmological Examination: To assess for signs of CMV retinitis and other eye complications.

HIV Infection: Treatment

• Aims of Treatment:
  • Prevent immune deterioration: To reduce the risk of opportunistic infections and malignancies.
  • Reduce viral load: To minimize viral replication and slow disease progression.
• Treatment Considerations:
  • Stage of disease: The treatment regimen depends on the progression of HIV infection.
  • Concomitant opportunistic infections: Existing infections may require specific treatment considerations.
  • CD4 counts: CD4 cell counts guide treatment decisions and monitor disease progression.