Newer Agents for the Treatment of HIV Infection

Despite the many advances in the understanding of the HIV virus and its treatment, there is not yet a cure for the infection. Emergent resistance to clinically proven drugs such as the reverse transcriptase inhibitors and (he protea.se inhibitors has complicated the picture of good (herapeutic targets. The idea of using a vaccine os a therapeutic tool has 

Successes with vaccines of the live/attenuated (low-virulence). killed whole virus or (he recombinant coat protein types have primarily involved acute viral diseases in which a natural infection and recovery lead to long-term immunity. 

The failure of (he first generation of AIDS vaecines la to a reexamination of the whole AIDS vaccine effort. Ai. guide forresearch efforts, a number of criteria foran idd AIDS vaccine have been developed. The ideal AIDSvx-cine should (a) be safe, (b) elicit a protective immune n sponse in a high proportion of vaccinated individuals, lei stimulate both cellular and humoral branches of (he immim  

Cloned HIV-1 reverse tran.scriptasc facilitates the study of Ihe cfTccts of a novel compound on the kinetics of the enzyme. Random screening of chemical inventories by the phannuceutical industry has led to the di.scovery of several NNRTIs of the enzyme. Thc.se inhibitors represent several Miuclurally di.stinct classes. The NNRTIs share a number of common biochemical and pharmacological properties.  

Delavirdine. Dclavirdine (Rescriptor) must be u.sed with at least two additional antiretroviral agents to treat HI V-I infections. The oral ab.sorption of dclavirdine is rapid, and peak plasma concentrations develop in I hour. Extensive mctaboli.sni occurs in the liver by cytochrome P-450 (CYP) isozyme 3A (CYP 3A) or pos.sibly CYP 2D6. Bioavailability is 85%. Unlike nevirapine, which is 48%. protein bound, dclavirdine is more than 98% protein bound. The half-life is 2 to II hours, and elimination is 44% in feces. 51% in urine, and lc.ss than 5% unchanged in urine. Dclavirdine induces its own mctaboli.sm. Oral dosage forms are. supplied as a 200-mg capsule and a lOO-ing tablet. 

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