HIV pathogenesis and treatment strategies.

HIV infection is a chronic progressive illness. This virus has a multiplicity of cellular targets and the virus-host relationship changes over time. The high daily rate of virus production is initially controlled by the immune system, but eventually the immune system fails to contain viral replication and individuals become susceptible to a range of opportunistic infections. The course of the disease is improved by chemotherapeutic intervention with antiretroviral drugs, but the major limiting factor in the effective control of viral replication is the emergence of resistance of these agents. Using the phenomenon of "resistance reversal" in which resistance mutations to one drug reverse the effect of resistance mutations to another drug, researchers have identified promising combinations of antiretrovirals for clinical use. Application of the scientific understanding of HIV pathogenesis is essential if new and successful therapeutic approaches are to be developed. A wide range of antiretroviral drugs is now available for combination therapy studies. The criteria for their selection and combination should include synergy, different sites of activity in the body, lack of cross- resistance, resistance reversal, and no overlapping toxicities. Ultimately, there must be consensus in initiating treatment during the early stages of infection while the immune system is still functional, and treatment should involve the use of a combination of antiretroviral agents.