What is Human Immunodeficiency Virus (HIV)?

Human Immunodeficiency Virus (HIV)

HIV is a retrovirus that primarily targets CD4+ T lymphocytes, leading to progressive immune system deterioration, which if untreated, results in acquired immunodeficiency syndrome (AIDS) characterized by opportunistic infections and malignancies. 1

Pathophysiology of HIV Infection

HIV infection follows a specific pathological process:

1. Viral Entry and Replication:

   • HIV enters cells by binding its envelope glycoprotein gp120 to CD4 receptors on immune cells, followed by co-receptor binding and membrane fusion mediated by gp41 1
   • Primary targets are CD4+ T lymphocytes, monocytes/macrophages, and dendritic cells
   • After entry, viral RNA is reverse-transcribed into DNA, integrated into the host genome, and used to produce new viral particles

2. Disease Progression:

   • Acute Infection: Characterized by high viral replication, rapid CD4+ T cell decline, and flu-like symptoms
   • Clinical Latency: Period of sustained immune activation with gradual CD4+ T cell decline, often asymptomatic for years
   • Advanced Disease/AIDS: Profound CD4+ T cell depletion (<200 cells/mm³) leading to opportunistic infections and malignancies 1

Epidemiology and Transmission

HIV is transmitted through specific routes:

• Sexual contact: Exchange of bodily fluids during unprotected sexual activity
• Blood exposure: Sharing needles, accidental needlesticks, or receiving contaminated blood products
• Perinatal transmission: From mother to child during pregnancy, delivery, or breastfeeding 2

The risk of disease progression varies significantly based on viral load and CD4+ T cell counts:

• Patients with CD4+ counts of 200-350 cells/mm³ and viral loads >55,000 copies/mL have a 64.4% 3-year risk of progression to AIDS 2
• Even at higher CD4+ counts (>350 cells/mm³), high viral loads substantially increase progression risk 2

Diagnosis of HIV Infection

HIV testing typically follows a specific algorithm:

1. Initial Screening: Enzyme-linked immunosorbent assay (ELISA) or rapid antibody test
2. Confirmation: Western blot or immunofluorescence assay for positive screening tests
3. Special Considerations:
   • HIV antibody is detectable in ≥95% of patients within 6 months of infection
   • Negative antibody tests cannot rule out infection acquired less than 6 months prior 2

Important testing principles:

• Informed consent must be obtained before HIV testing
• Positive tests require medical and psychosocial evaluation and follow-up services 2
• Rapid HIV antibody testing is highly accurate (sensitivity and specificity ≥99%) and particularly useful for screening high-risk patients who don't receive regular medical care 2

Clinical Manifestations

HIV infection presents with a spectrum of manifestations:

1. Early/Acute Infection: Often flu-like symptoms (fever, lymphadenopathy, rash)
2. Chronic Asymptomatic Infection: Minimal or no symptoms despite ongoing viral replication
3. Advanced Disease/AIDS: Characterized by:
   • Opportunistic infections (Pneumocystis pneumonia, tuberculosis)
   • Malignancies (Kaposi's sarcoma, lymphomas)
   • Neurologic complications (HIV-associated neurocognitive disorders)
   • Constitutional symptoms (wasting, fever, diarrhea) 2, 1

Complications Beyond Immunodeficiency

HIV infection affects multiple organ systems:

• Cardiovascular: Increased risk of coronary artery disease due to inflammation, immune activation, and endothelial injury 2
• Gastrointestinal: Intestinal mucosal damage with breakdown of intestinal barrier and microbial translocation 1
• Neurological: Direct viral infection of CNS causing a spectrum of neurocognitive disorders 1
• Renal: HIV-associated nephropathy, particularly in individuals of African ancestry 1

Treatment Principles

The goals of antiretroviral therapy (ART) are to:

1. Suppress viral replication
2. Restore immune function
3. Reduce HIV-associated morbidity and mortality
4. Prevent HIV transmission

Key treatment considerations:

• Early initiation of ART is recommended regardless of CD4+ count
• ART regimens typically combine drugs from different classes to prevent resistance
• Common antiretroviral medications include:
  • Tenofovir: A nucleotide reverse transcriptase inhibitor that prevents viral DNA synthesis 3
  • Efavirenz: A non-nucleoside reverse transcriptase inhibitor that blocks viral replication 4

Important Precautions

• Medication side effects: Monitor for hepatotoxicity, renal dysfunction, bone mineral density loss, and neuropsychiatric symptoms 4, 3
• Drug interactions: Significant interactions can occur between antiretrovirals and other medications
• Pregnancy considerations: Special considerations for preventing mother-to-child transmission while minimizing fetal exposure risks 4

Prevention Strategies

Effective prevention methods include:

• Consistent and correct use of barrier methods (condoms)
• Pre-exposure prophylaxis (PrEP) for high-risk individuals
• Post-exposure prophylaxis (PEP) after potential exposures
• Treatment as prevention (viral suppression in HIV-positive individuals)
• Avoidance of needle sharing
• Prevention of mother-to-child transmission through maternal ART 2

Despite significant advances in treatment and prevention, HIV remains a major global health challenge requiring ongoing research for a definitive cure and vaccine.