HIV is a virus that affects the immune system and can progress to AIDS if a person does not receive treatment. Due to medical advances and understanding the life cycle of HIV, medications are available that can inhibit viral replication and prevent the development of AIDS.

Since the first reports of HIV in 1981, the World Health Organization (WHO) estimates that around 37 million people have died from the virus. While it is now treatable, there is currently no cure for HIV, and it is a life-long illness. Evidence notes that nearly 38 million people were living with the disease in 2020, and 1.5 million became infected in the same year.

Current treatments aim to prevent the progression of the infection by disrupting HIV at different phases of its life cycle. Using these treatments can reduce the risk of transmission, extend a person’s life expectancy, and improve their quality of life.

In this article, we discuss the life cycle of HIV, how it affects medication, and the timeline of a HIV infection.

An image of HIV viruses via a transmission electron microscope.Share on Pinterest
BSIP/UIG Via Getty Images Hiv Virus Responsible For Aids Virus, Made According To A View Under Transmission Electron Microscope

When talking about viruses such as HIV, the life cycle refers to the steps the virus takes to replicate and spread. Viruses spread by infecting a host cell, then using it to produce copies of itself and releasing those copies.

Broadly, this process falls under three stages: entry, genome replication, and exit. While different viruses use different strategies to replicate and spread, they all go through these steps to do so. HIV has a particularly complex life cycle due to its unique viral structure.

The structure of HIV plays an important role in its life cycle. HIV is an enveloped virus, meaning that it has an outer lipid membrane. This outer wall features glycoproteins, which are key to the virus’ ability to replicate. Just inside this membrane is the matrix protein layer, and within is another internal capsule called the capsid.

Within the capsid are two strands of ribonucleic acid, or RNA, which hold HIV’s genetic material. Not to be confused with DNA, RNA is a single-strand protein. The capsid also contains enzymes, such as reverse transcriptase, integrase, and protease, which are essential for HIV replication.

Some people may also refer to this as the replication cycle. The 7 stages of the HIV life cycle include:

  1. Binding: The HIV virus fuses to the surface of its target cell, the CD4 lymphocyte. It uses its external glycoproteins to attach to receptors on the cell surface.
  2. Fusion: The outer membrane and matrix protein layer of the virus fuse with the CD4 cell membrane. This allows it to release its inner capsid into the cell.
  3. Reverse Transcription: The virus uses the reverse transcriptase enzyme to convert its RNA into DNA. As viral DNA, the virus is now able to enter the nucleus of the cell.
  4. Integration: Now inside the nucleus, HIV DNA inserts itself into the hosts’ own genetic code. It does this using the integrase enzyme.
  5. Replication: The virus uses the cell’s replication system to create more of itself in the form of HIV proteins.
  6. Assembly: These new HIV proteins, along with HIV RNA, congregate near the surface of the cell membrane. Together they have the tools to create immature, noninfectious HIV.
  7. Budding: These new HIV components push out of the cell membrane. Once out of the cell, the protease enzyme changes immature HIV into its mature, infectious form.

HIV medications disrupt the virus by targeting its life cycle at different stages. The problem is that HIV replicates very quickly. This gives it more opportunities to make mistakes in its own genetic code, and these mutations can make it resistant to a single medication over time.

Because of this, a doctor may use several classes of medications to halt the virus at different phases of its life cycle. This is the philosophy behind highly active antiretroviral therapy (HAART).

The first drug to be approved for HIV treatment was zidovudine, or AZT, in 1987. AZT targets the virus in its third stage of writing itself from RNA into DNA. By inhibiting reverse transcriptase, AZT prevents viral replication and protects normal cells. It falls under the category of nucleoside reverse transcriptase inhibitors (NRTIs).

Another class of HIV medications are protease inhibitors. These prevent immature HIV from maturing and replicating in its final life cycle stage. Examples of protease inhibitors include saquinavir (SQV) and darunavir (DRV).

Integrase strand transfer inhibitors (INSTIs) block the enzyme integrase, preventing the virus from writing itself into host DNA. Dolutegravir (DTG), cabotegravir (CAB), and raltegravir (RAL) are all examples of INSTIs.

Some medications use two classes of drug together, called combination medications. These can make it easier for people to manage their regimen, because people with HIV can be on several treatments that require them to take medications at specific times of the day. It is important that people with HIV take their medications every day to prevent the progression of the virus.

Click here to learn more about different types of HIV medications.

Treatments can now slow HIV from progressing to AIDS. However, treatment requires prompt testing and care after exposure to the virus. Despite improvements in treatment regimens, access to care remains a big problem. Even with the advent of multi-drug therapy, evidence reports that 680,000 people died from AIDS-related illness in 2020 alone.

When a person acquires HIV and does not receive treatment, the infection progresses through three stages:

Stage 1: Acute infection

After exposure to HIV, the virus is in its acute phase for 2–4 weeks. During this period HIV is infiltrating the body and invading the CD4 cells. Blood levels of the virus are high.

The body reacts to this assault with flu-like symptoms; people may experience headache, fever, and a rash, or they may have no symptoms at all. During this phase, there is high risk of transmitting the virus to another person.

Stage 2: Chronic infection

Some people may also refer to this stage as asymptomatic or latent HIV. During this time, the virus is still replicating through its life cycle, but doing so more slowly. People can live in this stage for years without any symptoms, not knowing that they have HIV.

This phase usually lasts a decade or more. However, people on HAART therapy may remain in this latent stage for longer. It is possible to pass HIV on to others if a person is not receiving or correctly taking this medication. Thankfully, the medication can reduce a person’s viral load and the risk of transmission down to undetectable levels.

Stage 3: AIDS

This is the final stage of HIV infection. At this point, the virus has attacked the immune system until it is no longer able to protect itself. People with AIDS are susceptible to infections that those without it can fight off much more easily, such as forms of pneumonia and cancer.

A person may receive a diagnosis with AIDS if they have one of these opportunistic infections, or when their CD4 cells reach a critically low level.

People with AIDS have high levels of the virus in blood and bodily fluids and the virus is extremely transmissible. People who cannot access treatment typically survive about 3 years in this stage before succumbing to a fatal complication. However, if they acquire an opportunistic illness, life expectancy without treatment falls to roughly 1 year.

Click here to learn more about the HIV timeline.

Due to the complex structure and life cycle of the virus, HIV is a chronic condition that is difficult to treat. By understanding the life cycle of the virus, researchers have developed treatments that can disrupt HIV at different phases and improve a person’s life expectancy and quality of life.