Antiretroviral Drugs Work
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.
Nucleotides linked together in a strand form a nucleic
common nucleic acids are ribonucleic
acid (RNA) and deoxyribonucleic acid (DNA).
- RNA is a chain of nucleotides, each composed of ribose (a five carbon sugar) + nitrogenous base (adenine, guanosine, cytosine or uracil) + phosphate.
- DNA is a double strand of nucleotides, each composed of deoxyribose (a five carbon sugar) + nitrogenous base (adenine, guanosine, cytosine or thymine) + phosphate.
DNA stores the instructions required for
reproduction, development and function. RNA is transcribed from the genes encoded in the DNA. Transcribed RNA forms a template upon which protein synthesis occurs. Cells respond to stimulus that cause DNA to transcribed a specific RNA template. The RNA translates a protein which produces the required cellular activity.
to a group of viruses called retrovirus. A retrovirus has
genes comprised of RNA. 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 transcribes its RNA genes
to form a double stranded DNA segment.
The viral enzyme integrase inserts the viral DNA into the host cell genome, completing the infection. Once embedded in the genome, viral DNA transcribes viral RNA. The viral RNA uses the host cell to produce viral components that will be assembled into a multitude of virion.
uses the viral enzyme reverse transcriptase to transcribe DNA from viral RNA.
Antiretroviral (ARV) drugs inhibit
the replication of HIV at various stages of its life cycle. Classes
of approved ARV drugs include:
reverse transcriptase inhibitors (NRTIs), interfere with
the production of viral DNA by substituting a synthetic nucleotide that has
been intentionally created to block the addition of a subsequent nucleotide. When an NRTI is added to the viral DNA chain it leads to a termination of viral DNA 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
- Fusion inhibitors currently
being developed bind to the transmembrane protein gp41. Binding prohibits
a gp41 conformational change necessary to fuse the virus to the target cell.
- Entry inhibitors Maraviroc (Selzentry®) is the first of a new class of medications targeting the CCR5 coreceptor on the CD4+ T-cell. Maraviroc binds to the CCR5 coreceptor stopping CCR5 tropic HIV-1 from securely attaching to the CD4+ T-cell.
- Integrase inhibitors block the ability of the HIV enzyme integrase from splicing the HIV DNA strand into the host cell genome.