HIV Basics

HIV-1, a lentivirus of the Retroviridae family, contains two copies of single-stranded RNA and key enzymes (reverse transcriptase, integrase, protease) within a p24 capsid protein core surrounded by a lipid envelope studded with gp120 and gp41 glycoproteins. Viral entry requires binding of gp120 to the CD4 receptor on T-helper lymphocytes, followed by conformational change exposing gp41 which binds the CCR5 or CXCR4 co-receptor. The CCR5-delta32 homozygous mutation provides near-complete resistance to R5-tropic HIV. After entry, reverse transcriptase converts viral RNA to DNA with high error rate (one mutation per replication cycle), driving viral diversity and drug resistance. Integrase inserts proviral DNA into the host genome, establishing the latent reservoir — integrated provirus in resting memory CD4+ T cells that is invisible to the immune system and not affected by ART, representing the primary barrier to HIV cure. Acute retroviral syndrome occurs 2-4 weeks post-infection with massive viremia, CD4 destruction in gut-associated lymphoid tissue (GALT), and immune activation. The immune response partially controls viremia to a 'set point' viral load that predicts disease progression rate. Without ART, CD4 count declines ~50-70...