Definition of Human Immunodeficiency Virus (HIV)
HIV (Human Immunodeficiency Virus) is an RNA virus that targets CD4+ T cells, causing immune dysfunction and eventually leading to acquired immunodeficiency syndrome (AIDS) if left untreated. 1
Formal Classification and Structure
- HIV is a retrovirus belonging to the Lentivirus genus that contains three major genes encoding capsid proteins (gag – p55, p24, p17), enzymes (pol – p66, p51, p31 including reverse transcriptase, protease, and integrase), and envelope glycoproteins (env – pg160, gp120, gp41) 1
- HIV is classified into two types: HIV-1 and HIV-2, with HIV-1 being more common in the United States 1
- HIV-1 is further categorized into groups M (most common), O, N (non-M, non-O), and P 1
- The virus uses CD4 as its primary cellular receptor, which is found mainly on T helper lymphocytes and cells of the monocyte/macrophage lineage 2
Diagnostic Definition
- The standard diagnostic definition for HIV infection involves repeatedly reactive immunoassay followed by confirmatory Western blot or immunofluorescent assay, with sensitivity and specificity greater than 99% 1
- Alternative FDA-approved testing methods include:
- Rapid HIV antibody tests (sensitivity 96-100%, specificity >99.9%)
- Combination tests for p24 antigen and HIV antibodies
- Qualitative HIV-1 RNA tests 1
- HIV infection can be detected through:
- HIV RNA (viral load) testing, which becomes positive first (3-5 days before p24 antigen)
- p24 antigen detection, which becomes positive before antibody tests
- Antibody testing, which typically becomes positive within the first four weeks after exposure 1
Clinical Definition and Classification
- The CDC classification system for HIV-infected adults categorizes infection based on CD4 cell count and clinical conditions:
- Category A: Asymptomatic, persistent generalized lymphadenopathy, or acute HIV infection
- Category B: Symptomatic conditions not in Category A or C
- Category C: AIDS-indicator conditions 1
- CD4 count stratification:
- 1: ≥500 cells/mm³ (≥29%)
- 2: 200-500 cells/mm³ (14-28%)
- 3: <200 cells/mm³ (<14%) 1
Pathogenic Mechanism
- HIV primarily infects CD4+ T cells through binding to the CD4 receptor and subsequent fusion with the cell membrane 3
- The virus can destroy CD4+ T cells through:
- Cells of the macrophage lineage generally serve as viral reservoirs rather than being destroyed 2
- HIV causes functional impairment in T cells, B cells, and monocytes, leading to progressive immune dysfunction 2
- The virus can exist in latent or chronic forms, contributing to viral persistence despite treatment 2
Clinical Course
- HIV infection typically progresses through several phases:
- Inefficient viral transmission
- Acute phase with intense viral replication and dissemination to lymphoid tissues
- Chronic, often asymptomatic phase with sustained immune activation and viral replication
- Advanced phase with marked depletion of CD4+ T cells leading to AIDS 3
- Without treatment, almost all infected individuals will eventually develop AIDS, defined by severe T cell depletion and the occurrence of over 20 conventional degenerative and neoplastic diseases 5
Monitoring and Management
- HIV viral load and CD4+ T cell counts are the primary markers used to determine when to initiate antiretroviral therapy and to monitor treatment efficacy 1
- HIV viral suppression is defined as a viral load persistently below the level of detection of the assay (typically 20-80 copies/mL) 1
- Resistance testing is strongly recommended upon initiation of care and for patients experiencing virologic failure 1
This formal definition encompasses the virological, immunological, and clinical aspects that characterize HIV infection, providing a comprehensive framework for understanding this pathogen and its effects on the human immune system.