1983: Isolation of the AIDS Virus
The first big breakthrough in the battle against AIDS occurred in 1983, with the isolation of HIV-1,[3,4] followed by the development and implementation of a blood-screening antibody test indicating the presence or absence of this virus. The discovery immediately raised hopes that therapies directly targeting this human retrovirus would soon be discovered and become available to infected individuals. The first such therapy was zidovudine, a nucleoside analog that inhibits HIV-1 reverse transcriptase, which was approved by the FDA in 1987. HIV-1 must be integrated into the host DNA to be able to use the host cells' genetic machinery to produce new virus. HIV-1 single-stranded viral RNA is first converted to double-stranded DNA by reverse transcriptase. The nucleoside reverse transcriptase inhibitors (NRTIs) interfere with HIV-1 replication by competitively inhibiting this enzyme, thus leading to chain termination of HIV-1 proviral DNA[7,8] (Fig. 2).
NRTIs and NNRTIs: mechanisms of action. HIV-1 must be integrated into the host DNA to be able to use the host cells' genetic machinery to make new progeny virus. HIV-1 single-stranded viral RNA is first converted to double-stranded DNA by reverse transcriptase. (a) The NRTIs interfere with HIV-1 replication by competitively inhibiting reverse transcriptase, thus leading to chain termination of HIV-1 proviral DNA. (b) NNRTIs are a group of structurally diverse agents that bind at a position distant from the active site, resulting in conformational changes at the active site with a resultant inhibition of reverse transcriptase. This figure is modified from (Ref. 8).
Nat Med. 2003;9(7) © 2003 Nature Publishing Group
Cite this: Twenty Years of Therapy for HIV-1 Infection - Medscape - Jul 01, 2003.