possible to minimize the morbidity and mortality associated with HIV, to delay or prevent the onset of AIDS, and to allow those infected to lead a productive life.

Goals of Antiretroviral Therapy

  • viral load suppression

  • restoration or preservation of immunologic function

  • quality of life improvement

  • reduction in HIV related morbidity and mortality

SOURCE: U.S. DHHS, 2003.

Restoration of immune function and suppression of viral replication have been assessed largely by laboratory criteria. The goal of therapy is to achieve a CD4 cell count of greater than 200 copies/mm3 and an “undetectable” viral load (less than < 50 copies/mL). Within 4–6 months of starting antiretroviral therapy, these goals should be achieved. Failure is multifactorial; some issues will be highlighted in this report.

The Four Classes of Therapy: Mechanisms of Action

Drugs used to treat HIV principally belong to hree main classes, each based on a different mechanism of action; a fourth class was recently added. Three of the classes affect viral enzymes. The fourth class affects the ability of the virus to enter target cells in the body. The first class developed was the nucleoside analogue reverse transcriptase inhibitors (NRTIs). The first drug in this class (zidovudine [AZT or ZDV]) was introduced in 1987. The NRTIs compete with physiologic nucleosides—the building blocks of host and viral DNA—for binding to the reverse transcriptase enzyme. This has the effect of interrupting viral DNA chain elongation. There are eight FDA approved drugs in this class. The next two classes of drugs were introduced in late 1995 to mid-1996. One of these is the nonnucleoside reverse transcriptase inhibitors (NNRTIs). The NNRTIs bind to the reverse transcriptase enzyme and change the “shape” of the enzyme thereby preventing the enzyme’s action of transcribing viral RNA into viral DNA. There are three FDA-approved drugs in this class. The other class of drugs that was introduced is the protease inhibitors (PIs). The PIs work at a later stage of new virus production. The PIs inhibit the viral enzyme that cleaves a polypeptide protein necessary to produce new mature infectious virus particles. Virions treated with PI’s do not become infectious. There are eight



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