Antiretroviral drugsBMJ 2001; 322 doi: http://dx.doi.org/10.1136/bmj.322.7299.1410 (Published 09 June 2001) Cite this as: BMJ 2001;322:1410
- Ian V D Weller,
- I G Williams
The clinical effectiveness of antiretroviral therapy has improved markedly over the last few years. Since 1996 in the developed world there have been dramatic falls in the incidence of new AIDS cases and AIDS associated deaths. Published data in the late 1990s estimated the mortality rate in patients with CD4 counts of less than 100 × 106/l had fallen by nearly two thirds to <8 per 100 patient years. Although the long term clinical efficacy of the current antiretroviral treatment regimens remains uncertain, the biological rationale for maintaining a clinical response has been established. Sustained inhibition of viral replication results in partial reconstitution of the immune system in most patients, substantially reducing the risk of clinical disease progression and death. Reservoirs of HIV in latently infected resting T lymphocytes and other long lived cell populations make it unlikely that HIV can be eradicated by antiretroviral therapy alone. Strategies to sustain suppression of viral replication in the long term will be necessary.
This article has been adapted from the forthcoming 5th edition of ABC of AIDS. The book will be available from the BMJ bookshop and at http://www.bmjbooks.com/
There are several potential targets for antiretroviral drugs in the viral replication cycle. Three classes of antiretroviral drugs are currently used in combination for the treatment of HIV infection, which target the activity of two viral enzymes. New therapeutic agents are constantly being evaluated.
Targets for antiretroviral therapy
Reverse transcriptase inhibitors
The first drugs made available for clinical use were inhibitors of the HIV reverse transcriptase. Before the virus can be integrated into the host cell genome DNA, a copy of the viral RNA has to be formed (proviral DNA). This is regulated by the specific HIV DNA polymerase: reverse transcriptase. If a DNA copy is not formed, the viral RNA genome becomes susceptible to …