Clinical meaning
Human immunodeficiency virus (HIV) is a retrovirus that selectively infects and destroys CD4+ T-helper lymphocytes, the central coordinators of adaptive immunity. HIV-1 is responsible for the global pandemic, while HIV-2 is predominantly found in West Africa and progresses more slowly.
The HIV replication cycle involves several targetable steps. The virus binds to the CD4 receptor on T-helper cells via its gp120 envelope glycoprotein. Conformational change then exposes the gp41 protein, which binds to a co-receptor — either CCR5 (used by R5-tropic strains, predominant in early infection) or CXCR4 (used by X4-tropic strains, associated with more rapid progression). Individuals homozygous for the CCR5-delta-32 mutation (approximately 1% of Northern European descent) have natural resistance to HIV infection. After membrane fusion and viral entry, the enzyme reverse transcriptase converts viral RNA to double-stranded DNA. This process is error-prone, generating approximately one mutation per replication cycle, which drives rapid viral evolution and resistance development. The viral DNA is then integrated into the host cell genome by the enzyme integrase, creating a provirus that persists for the lifetime of the cell. Integrated proviral DNA is transcribed to produce viral RNA and proteins, which are assembled at the cell membrane. The protease enzyme cleaves polyprotein precursors into functional viral proteins, and mature virions bud from the cell surface.
Without treatment, HIV produces approximately 10 billion virions daily, with a viral half-life of only 6 hours, creating enormous replication and mutation capacity. CD4+ T-cell counts decline at approximately 50-80 cells/microL per year. Normal CD4 count is 500-1500 cells/microL. When CD4 falls below 200 cells/microL, or an AIDS-defining illness occurs, the patient has progressed to AIDS (Acquired Immunodeficiency Syndrome). Opportunistic infections emerge at specific CD4 thresholds: Pneumocystis jirovecii pneumonia (PCP) below 200, Toxoplasma gondii encephalitis below 100, Mycobacterium avium complex (MAC) and CMV retinitis below 50 cells/microL.