Pathophysiology
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...