used ones along with drug rehabilitation efforts and education about use of condoms and other safer sexual practices.
Even without a vaccine, better prevention and treatment of opportunistic infections, and better antiviral therapy against HIV have significantly lengthened the asymptomatic stage of the disease and prolonged life once AIDS develops (figure 29.10). Advances in antiviral treatment mainly result from the development of new medications with different modes of antiviral action, and use of these medications in "cocktails," combinations of reverse transcriptase and protease inhibitors referred to as HAART, "highly active antiretroviral therapy." Other important advances include the combining of medications in a single dosage form, and developing "once-a-day therapy." The effectiveness of HAART probably stems from the fact that each of the medications act on the replicating virus at different parts of the virus life cycle, and despite the high mutation rate of HIV, it is much less likely that any one mutant could develop resistance to all the medications at the same time. Presently available medications fall into two groups: inhibitors of reverse transcriptase and inhibitors of viral protease. Other types of medications being developed are fusion inhibitors to prevent viral entry into host cells, integrase inhibitors that prevent entry of the viral genome into host chromosomes, and medications that interfere with polyproteins.
Medications that interfere with reverse transcriptase fall into two categories, nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI). Zidovudine (AZT), stavudine (D4T), and lamivudine (3TC) are among the half dozen NRTIs in wide use, and a number of others are undergoing clinical trials. All are nucleoside analogs, but they differ chemically and in their site of action on the enzyme. These substances owe their effectiveness to their resemblance to the normal purine and pyrimidine building blocks of nucleic acids. During nucleic acid synthesis, the viral reverse transcriptase enzyme incorporates the medication molecule into the growing DNA chain, thereby blocking completion of the DNA strand. This process for AZT is illustrated in figure 29.11. ■ nucleosides, figure 2.22, p. 32
As for the non-nucleoside inhibitors of reverse transcriptase, nevirapine, efavirenz, and delavirdine are among those in
Adenine nucleotide is added to part a, . and AZT is added to part b.
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