potent against a pathogen is also severely toxic to the host and is therefore not usable. With the hope of finding a balance between efficacy and toxicity, scientists try to focus on activities that the bacteria or virus carries out that the host cell does not. Scientists often dissect the steps involved in infection and reproduction and ask whether they can block each one.

For HIV the first interaction that scientists would hope to interrupt is the binding between the gp120 molecule on the virus and the CD4 receptor on the host cell. Some researchers have proposed using antibodies that recognize and bind gp120, in effect forming a cap that prevents access to CD4. The use of antibodies, however, begs the variability issue. To circumvent that, researchers have investigated the feasibility of using CD4 as a cap. They know that despite variations in gp120, it always recognizes CD4 and binds to it. Their hope was that soluble CD4 molecules would effectively tie up all of the viral gp120 molecules, and none would be available to bind to CD4 on cells. Unfortunately, this very clever strategy has not worked as anticipated. Through their studies the inventors of this strategy have discovered that to be effective, much higher quantities of CD4 must be administered than is practical.

The next opportunity to interrupt the viral life cycle would be in the uncoating stage, but no drugs have been developed to prevent this yet. It is in the next stage, where the virus converts its genes into DNA from RNA, that drug developers have had the greatest success in controlling HIV. Drugs that interrupt viral DNA synthesis act to inhibit the enzyme called reverse transcriptase, which effects the RNA to DNA conversion. AZT is the oldest of the reverse transcriptase inhibitors and is most commonly given to people when they have fewer than 500 helper T-cells per microliter of blood. This drug and its close relatives dideoxycytosine (ddC) and dideoxyinosine (ddI) work through a trick they play on the reverse transcriptase enzyme.

These drugs closely resemble the actual nucleic acid subunits that are strung together to make long chains of DNA, so the reverse transcriptase tries to incorporate them into the growing DNA molecule. However, a quirk in the chemistry of these nucleic acid analogs allows them to be added onto the DNA chain, but they themselves cannot form bonds with any incoming nucleic acid, meaning that they terminate DNA chain growth. The truncated pieces of viral DNA so produced are virtually useless and cannot direct the synthesis of new viral particles.

AZT seems to slow the progression of AIDS once symptoms do appear and may reduce the number of opportunistic infections that



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