Understanding HIV Drugs Involves Understanding The HIV Life Cycle

To understand how different HIV medications work, it is helpful to be familiar with the life cycle of the HIV virus. All viruses are like “parasites”. They cannot live outside of a host, and they need to infect a host cell to replicate. Once inside a cell, a virus will “hijack” the cells machinery to manufacture new viruses.

The HIV Life Cycle

HIV infects cells of the immune system. These cells have receptors on their surface called CD4; they are collectively called CD4 cells. The main target of HIV is the T-helper cell (also called a T4-lymphocyte). The T-helper cell is responsible for warning the immune system that there are pathogens (in this case HIV) present.

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1) Binding and Fusion

Once the virus binds to the T-helper cell, it fuses with the cell. HIV then enters the cell and releases its RNA (genetic material) into the cell. This entry can be inhibited by entry inhibitors (enfuvirtide and maraviroc). The viral RNA then takes over the T-helper cell and turns it into a HIV “factory”.

DNA versus RNA

DNA and RNA are both genetic material. DNA is like a “blueprint” to create RNA. The RNA is then used to make proteins. Both are present in the nucleus of the cell.

2) Reverse Transcription

A HIV enzyme, called reverse transcriptase, converts HIV RNA into HIV DNA. This is called reverse transcription, because instead of DNA being used to make RNA, the viral RNA is used to make viral DNA. Reverse transcription can be blocked by nucleoside and nucleotide reverse transcriptase inhibitors (emtricitabine, lamivudine, zidovudine, stavudine, abacavir, tenofovir, and didanosine) and non-nucleoside reverse transcriptase inhibitors (efavirenz, rilpivirine, etravirine, delavirdine, nevirapine).

3) Integration

The newly formed HIV DNA is transported to the T-helper cell nucleus, and a HIV enzyme, called integrase, “hides” the DNA. Integrase incorporates the viral DNA into the T-helper cell’s DNA. At this point the integrated HIV DNA is called a provirus. This step can be blocked by integrase inhibitors (raltegravir and elvitegravir).

4) Transcription

A T-helper cell enzyme, called RNA polymerase, is then directed to make copies of HIV genetic material which will ultimately become long chains of HIV proteins. There are no approved drugs to inhibit this stage of the life cycle; however, research is being conducted to develop new drugs that will effectively block this step.

5) Assembly

A HIV enzyme, called protease, then cuts up the long protein chains into smaller protein molecules. These will be used to create HIV enzymes or structural components of the new virus particles. Assembly can be inhibited by protease inhibitors (tipranavir, indinavir, saquinavir, lopinavir, fosamprenavir, ritonavir, darunavir, atazanavir, and nelfinavir).

6) Budding

The newly created virus pushes out (“buds”) from the host T-helper cell. These new viruses must mature before they become infectious. This involves the processing of viral proteins. There are currently no drugs that block maturation; however, this is an area of ongoing research.

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