Antiretroviral Drugs

Antiretroviral Drugs

1. Definition, scope & therapeutic goal

• Antiretroviral (ARV) drugs are agents active against human immunodeficiency virus (HIV), a lentivirus (a subfamily of retroviruses evolved for chronic, persistent infection with gradual symptom onset); they prolong and improve quality of life and postpone AIDS complications but do not cure the infection — because the HIV genome integrates into host DNA, eradication is impossible with current agents (KDT 8e Ch.60, pp.860–1; G&G 14e Ch.64, pp.1245–6).
• Goal of therapy is maximal and durable suppression of viral replication — plasma HIV-RNA below the lower limit of quantitation (undetectable, usually <20–50 copies/mL) for as long as possible; the greater the suppression, the lower the chance of emergence of resistant virus (KDT 8e Ch.60, p.868; DiPiro 12e Ch.148, pp.2133–4; G&G 14e Ch.64, p.1246).
• An equally important outcome is a rise in CD4⁺ T-lymphocyte count, which closely correlates with reduced risk of opportunistic infections (OIs) (DiPiro 12e Ch.148, p.2129).
• Lifelong treatment is required; therapy is complex, expensive, and demands strong patient motivation and adherence (KDT 8e Ch.60, p.867; G&G 14e Ch.64, p.1245).
• With early-instituted, adherent ART, the life expectancy of an HIV-infected individual approaches that of an uninfected person (KDT 8e Ch.60, p.868; G&G 14e Ch.64, p.1245).
• Two species: HIV-1 (causes most of the global epidemic, genetically diverse with ≥5 clades; group M subtype B predominates in North America/W. Europe) and HIV-2 (closely related to simian immunodeficiency virus [SIV], concentrated in western Africa, less virulent/transmissible). Both have similar sensitivity to most ARVs except NNRTIs and enfuvirtide, which are HIV-1-specific and inactive against HIV-2 (G&G 14e Ch.64, p.1245; Harrison 21e Ch.208; Katzung 16e Ch.49, p.916).