HIV 12 - Life Cycle
The goal of antiretroviral therapy (ART) is to suppress HIV and, by doing so, to make sure that people living with HIV can enjoy long and healthy lives. To understand how ART works, it is important to first understand how HIV infects the body once the virus has entered it. This is called the life cycle of HIV.1,2
Most commonly, the virus enters the body when an HIV-negative person has unprotected sex with an HIV-positive person with a virus that is not suppressed.
- ENTRY INHIBITORS stop the virus from entering the CD4 cell (Step 2) e.g. maraviroc (MVC).
- NUCLEOS(T)IDE REVERSE TRANSCRIPTASE INHIBITORS act as fake substrates and stop the DNA forming in Step 3 e.g. abacavir (ABC), didanosine (ddI),
emtricitabine (FTC), lamivudine (3TC), stavudine (d4T), zidovudine (AZT) and tenofovir (TDF).
- NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS stop the enzymes from working in Step 3 e.g. efavirenz (EFV), etravirine (ETV), nevirapine (NVP) and rilpivirine (RPV).
- INTEGRASE STRAND INHIBITORS stop the HIV from being added into the cell’s DNA (Step 4) e.g. dolutegravir (DTG) and raltegravir (RAL).
- PROTEASE INHIBITORS stop the ‘cutting up’ needed to make new HIV in Step 6 e.g. atazanavir (ATV), darunavir (DRV), fosamprenavir (FPV), lopinavir/ritonavir (LPV/r), ritonavir (RTV) and saquinavir (SQV).
ART is made up of ARVs (antiretrovirals) from at least two classes which, together, act to suppress the HIV in the body.1
The ARVs can be given as separate medicines or combined into one tablet, also called FDCs (fixed dose combinations).
There is no cure for HIV, but it is treatable with ARVs and, when taken
properly and consistently, people with HIV can live long and healthy lives.
- BINDING: HIV makes its way to the body's CD4 cells - the cells that fight infection - and the virus attaches to the outer wall of the cell.
- FUSION: The virus fuses (joins together) with the CD4 cell, enters it and releases its contents (HIV RNA, where it carries its genes, and proteins/enzymes which will help to make more HIV) inside the CD4 cell.
*Fusion and entry inhibitors are HIV medicines (ARVs) that block this step of the HIV lifecycle, stopping multiplication of the virus eg Tenofovir, Efavirenz.
- REVERSE TRANSCRIPTION: One of the released viral materials is a protein called reverse transcriptase that allows the virus's genetic material to change from HIV RNA to HIV DNA.
*The nucleoside/nucleotide reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors are ARVs that block this step, stopping multiplication of the virus.
- INTEGRATION: The HIV DNA travels to the nucleus (the 'heart') of the CD4 cell where it uses another viral material, integrase, to combine the HIV DNA to the CD4 cell DNA *The integrase inhibitors are ARVs that block this step, stopping the virus from making more of itself e.g., dolutegravir and raltegravir.
- REPLICATION: Once HIV and CD4 cell DNA have combined, HIV uses the CD4 cell's machinery to produce long chains of HIV proteins. The HIV proteins are the building blocks of the new virus. *New ARVs are being developed to block this step, stopping the virus from making more of itself, e.g., lenacapavir.
- ASSEMBLY: The newly formed HIV proteins, including HIV RNA, travel to the surface of the CD4 cell and assemble (gather together) to form two immature viruses. Another one of the initially released viral materials, protease, cuts up these assembled long HIV protein chains to produce mature viruses.
*Proteases inhibitors are ARVs that block this step of the HIV lifecycle, stopping the virus from making more of itself e.g., atazanavir, darunavir and lopinavirlritonavir.
- BUDDING: The new mature HIV pushes out of the CD4 cell and the CD4 cell dies. This new HIV then moves into another CD4 cell, and the process starts again.
- ART (antiretroviral therapy) is the medicines that are taken to keep HIV under control.
- The ART are made up of ARVs (antiretrovirals) from at least two different classes which block HIV (human immunodeficiency virus) at different stages of the HIV life cycle.'
- The ARVs can be given as separate medicines or combined into one tablet or FDCs (fixed dose combinations).The goal of antiretroviral therapy (ART) is to suppress HIV and, by doing so, to make sure that people living with HIV can enjoy long and healthy lives.
- HIV is a virus that attacks the immune cells that fight infection called CD4 cells.
- HIV uses CD4 cells to multiply and spread throughout the body.
THIS PROCESS IS CALLED HIV REPLICATION. IT HAPPENS BILLIONS OF TIMES A DAY, IF A PERSON IS NOT ON ART (AND TAKING IT CORRECTLY).3
- AIDSINFO, National Institutes for Health (NIH). The HIV Life Cycle [Last reviewed September 28, 2020]. Available from: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-life-cycle. Last accessed May 2021.
- i-base. The HIV lifecycle in detail [Last reviewed March 11, 2021]. Available from https://i-base.info/guides/art-in-pictures/the-hiv-lifecycle-in-detail. Last accessed May 2021.
- NAM AIDSMap. HIV Lifecycle [Last reviewed November 2020]. Available from https://www.aidsmap.com/about-hiv/hiv-lifecycle. Last accessed June 2021.
- Rossiter, D. Ed. 2020. South African Medicines Formulary. Pretoria, South Africa: SAMA and Division of Clinical Pharmacology, UCT.