How Antiretroviral Drugs Work

All cells contain nucleic acids - complex molecules comprised of nucleotide chains that carry genetic information.

A nucleotide is an organic molecule consisting of a base, a sugar, and phosphate.

A nucleoside is similar, except it does not contain a phosphate.

The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA carries genetic instructions for the biological development of all cellular forms of life and for many viruses. RNA controls protein synthesis in living cells. Cells follow a plan that begins with DNA that is transcribed to RNA. The RNA is then translated to proteins.

HIV belongs to a group of viruses called retroviruses. A retrovirus has genes comprised of RNA molecules. Like all viruses, HIV "replicates" or "copies itself" within host cells. HIV is classified as a retrovirus because it uses the enzyme, reverse transcriptase, to convert its RNA genes into DNA genes.

Antiretroviral drugs inhibit the growth and replication of HIV at various stages of its life cycle. Classes of drugs available include:

• nucleoside reverse transcriptase inhibitors (NRTIs), interfere with the production of viral DNA by substituting a synthetic nucleoside with weak binding properties for a naturally occuring one. The weak bond leads to a break in the DNA chain and a termination of transcription.
• protease inhibitors (PIs), interfere with the maturation of HIV by preventing the cleavage of long protein strands into functional HIV components.
• non-nucleoside reverse transcription inhibitors (NNRTIs) work by binding to and altering the structure of the reverse transcriptase enzyme, so that it is unable to function properly.
• fusion inhibitors currently being developed bind to the transmembrane protein gp41. Binding prohibits a gp41conformational change necessary to fuse the virus to the target cell.

The National Institute of Allergy and Infectious Diseases provides an informative HIV replication diagram at the following link:

http://www3.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/hivReplicationCycle.htm