Roger J Pomerantz; David L Horn

Disclosures

Nat Med. 2003;9(7) 

In This Article

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.[5] 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.[6] 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).

Figure 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).

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