In this series we draw attention to recently licensed medicines with an entirely new mechanism of action. Publication does not imply endorsement of use in clinical practice. Copyright to the images belongs to Leiden University, but use of the images (available at http://coo.lumc.nl/trc) is free.
Maraviroc and raltegravir are two new drugs in the treatment of human immunodeficiency virus (HIV) infection, which target other action sites than the existing antiretroviral drugs (Figure 1). Nucleoside reverse transcriptase inhibitors and protease inhibitors belong to the classic therapy against HIV infection.
Maraviroc inhibits the formation of the binding complex at the surface of the host cell, preventing viral entry. The viral surface protein gp120 binds the CD4 receptor on the T cell. A second essential signal for viral entry is binding of gp120 to the coreceptor CCR5 of CXCR4. Completion of the binding complex makes it possible for protein gp41 to form a pore in the membrane of the T cell. Viral components can now penetrate the host cell. Maraviroc is a specific CCR5 antagonist that prevents CCR5-tropic HIV-1 entry (Figure 2). HIV-1 that uses CXCR4 as coreceptor is not affected by maraviroc.
Raltegravir inhibits the catalytic activity of the integrase enzyme, thereby preventing the insertion of viral DNA into the host cell genome. In this case, HIV does penetrate the T cell, but will not replicate, because the viral DNA will not be transcribed. Without replication and synthesis of viral particles the propagation of HIV infection is prevented (Figure 1).
The commonest adverse effects of maraviroc are diarrhoea, nausea and headache. Other common side-effects include dizziness, cough, insomnia, rash, weakness, muscle spasms and back pain.
A similar pattern of adverse reactions (gastrointestinal problems, asthenia and dizziness) is observed for raltegravir. Pruritus, lipodystrophy, hyperhidrosis and arthralgia are more specific adverse effects for raltegravir.
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