What is Human Immunodeficiency Virus (HIV)?

What is HIV?

HIV (Human Immunodeficiency Virus) is a retrovirus that specifically targets and destroys CD4+ T lymphocytes, progressively weakening the immune system and ultimately leading to AIDS (Acquired Immunodeficiency Syndrome) if left untreated. 1, 2

Viral Classification and Structure

• HIV is an RNA retrovirus belonging to the Lentivirus genus that contains three major genes encoding capsid proteins, enzymes, and envelope glycoproteins 2
• Two distinct types exist: HIV-1 (more common in the United States) and HIV-2, with HIV-1 further categorized into groups M, O, N, and P 2
• The virus has a unique life cycle involving reverse transcription of RNA to DNA, which then integrates into the host cell's genome 3

Mechanism of Immune Destruction

• HIV's primary cellular target is the CD4+ T lymphocyte, which serves as the key component for generating and regulating immune responses 4
• The virus binds to cells through the CD4 membrane glycoprotein receptor, found predominantly on helper T lymphocytes and cells of the monocyte/macrophage lineage 4
• HIV destroys CD4 cells through direct viral cytotoxicity and indirectly through host immune responses against infected cells 4
• Macrophage-lineage cells are generally not destroyed but serve as viral reservoirs, contributing to persistent infection 4
• The virus infects less than 1 in 10,000 T cells, yet causes progressive immune depletion over years 5

Natural History of Infection

• Initial transmission is generally inefficient, followed by an acute phase of intense viral replication and dissemination to lymphoid tissues 6
• A chronic, often asymptomatic phase follows, characterized by sustained immune activation and ongoing viral replication 6
• Without treatment, infection progresses over an average of 8 years from initial infection to AIDS, marked by severe CD4+ T cell depletion 1, 5
• The CNS becomes infected during the primary stage and remains infected throughout the course of disease in most untreated individuals 1

Clinical Spectrum

• Early infection may be asymptomatic despite active viral replication and immune system damage 6
• Progressive disease manifests as asymptomatic neurocognitive impairment, HIV-associated mild neurocognitive disorder (MND), and eventually HIV-associated dementia (HAD) 1
• Advanced AIDS is characterized by severe opportunistic infections including cryptococcal meningitis and primary CNS lymphoma 1
• AIDS is defined by severe T cell depletion and over 20 conventional degenerative and neoplastic diseases 5

Diagnostic Detection

• HIV infection can be detected through HIV RNA testing (becomes positive first, typically 3-5 days before p24 antigen), p24 antigen detection, and antibody testing 2
• Antibody testing typically becomes positive within the first four weeks after exposure, with ≥95% of patients showing detectable antibodies within 6 months 2, 7
• Standard diagnosis involves repeatedly reactive immunoassay followed by confirmatory Western blot or immunofluorescent assay, with sensitivity and specificity greater than 99% 2

Disease Monitoring Parameters

• CD4+ T cell counts and HIV viral load are the primary markers used to determine disease stage and guide treatment decisions 2
• CD4 count stratification includes three categories: ≥500 cells/mm³, 200-500 cells/mm³, and <200 cells/mm³ 2
• Viral suppression is defined as viral load persistently below the level of detection, typically 20-80 copies/mL 2

Treatment Impact

• Combination antiretroviral therapy (cART) suppresses viral replication and viremia, prevents or delays progression to AIDS, reduces transmission rates, and lowers HIV-associated mortality and morbidity 8
• However, cART does not eliminate HIV—an enduring pool of infected resting memory CD4+ T cells (latent HIV reservoir) is established early, requiring lifelong adherence to prevent viral rebound 8
• Where HAART is widely available, there has been profound reduction in the incidence and severity of HAD and major CNS opportunistic infections 1

Key Distinguishing Features from Other Viruses

• HIV is not HTLV-I or HTLV-II (Human T-Lymphotropic Viruses), which are different retroviruses that do not cause AIDS 1
• Unlike typical viral infections, HIV causes disease only after the onset of antiviral immunity (positive antibody test), following long and unpredictable asymptomatic intervals averaging 8 years 5
• The virus can exist in latent or chronic form, with mechanisms of viral persistence and conversion to productive infection still under investigation 4