Understanding the HIV Life Cycle: A Comprehensive Guide

Understanding the HIV life cycle has been vital to developing treatments that manage this lifelong condition. Human immunodeficiency virus (HIV) is an infection that attacks and damages cells of your immune system. If left untreated, HIV can eventually progress to AIDS or acquired immunodeficiency syndrome.


Data from the World Health Organization (WHO) indicates that HIV/ AIDS has killed approximately 40.1 million people since the onset of the epidemic. As of 2021, an estimated 38.4 million people were HIV positive, with 1.5 million individuals having been infected in the same year.

The HIV virus targets and destroys a type of white blood cell called CD4 cells. It uses the cells’ machinery to multiply and spread throughout the body. This process happens in a series of stages referred to as the life cycle of HIV.

Advances in HIV medications have transformed the once-terminal infection into a manageable chronic health condition. Current treatments have proven effective in stopping the different stages of HIV infection. Blocking any step in HIV’s life cycle means that the next stage can’t happen. Therefore, the infection is no longer able to multiply and spread.

In this article, we’ll cover the HIV life cycle, what happens during each stage, and the different medications that stop these processes. Read on!

HIV Transmission

Before we dive into the different stages in the lifecycle of HIV, we need to understand how this virus is transmitted.

HIV is primarily spread by;

  • Sexual contact – Vaginal or anal sex with an HIV-positive person is the leading mode of HIV transmission.
  • Blood contact – You may be exposed to infected blood by sharing needles, syringes, and other injection equipment.
  • Mother-to-child transmission – Mothers may pass on HIV to their babies during pregnancy, birth, or breastfeeding.

Now, you may be asking: How long does HIV live outside the body? The virus will survive for a few hours, and under the right conditions, a couple of days.

Anyone can get HIV. However, certain behaviors put you at a greater risk for exposure. These include;

  • Risky sexual behaviors
  • Untreated STDs increase the odds of an infection
  • Sharing injection equipment with other users

Is there anything you can do to reduce the risk of getting HIV? Yes. The following precautionary measures can help you better protect yourself.

  • Use condoms correctly during every sexual encounter
  • Talk to partners and get tested for HIV before engaging in unprotected sex
  • If you’re at risk for exposure to HIV, talk to your healthcare provider about using PrEP
  • Refrain from injecting drugs. However, if you do, ensure that you’re using sterile injection equipment

HIV Entry into Host Cells

So, how does a retrovirus like HIV enter a host cell? To better answer this question, we need to understand the structure of the HIV virus.

HIV is an enveloped virus. It has an outer lipid envelope in which protein “spikes” known as glycoproteins are embedded.

Just beneath this lipid membrane is the matrix protein layer. The matrix protein surrounds the capsid, the innermost capsule at the core of HIV.

The HIV capsid houses:

  • Ribonucleic Acid (RNA) – Retroviruses like HIV contain single-stranded RNA rather than double-stranded DNA. The RNA holds the HIV genetic information.
  • Enzymes – HIV uses different enzymes such as protease, reverse transcriptase, and integrase in the different stages of infection.

Now that we have a better understanding of how the HIV virus looks, we can look at how it enters the host cells. But first, what type of cells does the HIV virus attack?

Once HIV enters the body, it’ll need a host cell to multiply and spread. In this case, the host cells are CD4 cells, also referred to as helper T cells or T cells. CD4 cells are a type of white blood cells that fight off infections in the body.

HIV attaches itself to the membrane of the T cell through a process known as viral attachment or binding. During this stage, the spike-like glycoproteins on the HIV’s outer membrane will attach to a CD4 receptor and a coreceptor (either CCR5 or CXCR4). This creates a lock and key system, with the glycoproteins being the keys.

The next stage in HIV’s life cycle is known as binding. The virus will release its proteins into the cytoplasm or cellular fluid of the CD4 cells. This causes a fusion of the membrane of the CD4 cells and HIV’s envelope. Once fused, the virus can enter the host cell.

This HIV life cycle diagram sums up the different stages of infections.

HIV life cycle diagram

Reverse Transcription and Integration

As we’ve already mentioned, a pair of single-stranded RNA hold HIV’s genetic information. Before the reverse transcription process can start, the protective coating of the HIV RNA is dissolved. This process is called viral uncoating and it’s crucial for reverse transcription.

During reverse transcription, the virus releases the enzyme reverse transcriptase which converts RNA into the double-stranded DNA. This process allows the viral DNA to get into the nucleus of the T cell.

Once HIV enters the CD4’s cell nucleus it needs to combine its viral DNA with the cell DNA. To facilitate this integration, the virus releases the enzyme integrase.

The now integrated HIV DNA is referred to as provirus and it’s capable of hijacking and using the CD4’s genetic machinery.

HIV Replication

As the name implies, HIV creates copies of itself in this stage. During the replication cycle, HIV uses the host cell’s machinery to generate chains of viral protein. It also produces more of its genetic material, i.e., HIV RNA. This HIV protein is subsequently used to build more HIV.

HIV Assembly and Budding

The chains of viral protein and RNA created in the last stage assemble near the outer membrane of the CD4 cell. During this stage, the virus is immature and non-infectious.

Budding is the last step in the HIV life cycle. The immature HIV is pushed out of the host cell. HIV then releases another enzyme, protease. This enzyme is responsible for changing the structure of HIV proteins resulting in a mature and infectious virus. And once these virions are in free circulation they can target other T cells and the process repeats itself.

HIV Life Cycle and Immune Response

HIV compromises the immune system by targeting the CD4 cells. It uses the cells’ machinery to create copies of itself and these CD4 cells die shortly after. The newly created HIV virions find other CD4 cells and the process is repeated.

To try and counter the destruction of CD4 cells, the body’s immune response is to produce more T cells. However, the virus destroys these cells at a faster rate than the immune system is able to replace them. Ultimately, this will result in a low CD4 count and a high viral load.

A low CD4 count means a weakened immune system. Infections tend to last longer, occur frequently, re-occur more often and they are typically severe. This is because T cells are responsible for coordinating the immune response against infections. They trigger the response of other immune cells including macrophages, B cells, and CD8 cells in fighting off infections.

Over time, it has emerged that the HIV virus sometimes mutates (changes its form), especially during the replication process. When this happens, HIV proteins such as the enzymes reverse transcriptase, protease, and integrase are also altered. These changes may lead to drug-resistant HIV. Drug resistance means that medicine for HIV that was previously effective no longer helps manage the condition. Through drug-resistance testing, healthcare professionals can determine which HIV drugs are best suited for each patient.

Antiretroviral Therapy (ART), Emerging Treatments and Future Perspectives

HIV treatment regimens have improved dramatically over the past 26 years. Antiretroviral Therapy is currently used to control and manage HIV. It involves using a combination of medicines in at least two drug classes to reduce the amount of virus in the body. ART does not cure HIV. However, it prevents the multiplication and spread of the virus.

Most people using Antiretroviral Therapy are able to achieve viral suppression in just 6 months. In this state, their viral load is below 200 copies of the virus per milliliter of blood. Viral suppression makes HIV undetectable and significantly reduces the risk of transmission.

Types of Antiretroviral Drugs

Antiretroviral medications are grouped into different drug classes based on the stage of the HIV life cycle that they stop. Let’s take a look at the different types of ART drugs and how they inhibit the progression of HIV.

  • Entry inhibitors are a class of Antiretroviral drugs that blocks the entry of HIV into the host cells. They are further grouped into CCR5 inhibitors such as Maraviroc and fusion inhibitors such as Enfuvirtide.
  • Attachment and Post-attachment inhibitors stop the virus from attaching to CD4 cells and, therefore, gaining entry into the cells. Fostemsavir is an example of an attachment inhibitor while Ibalizumab is a post-attachment inhibitor.
  • Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of ART drugs designed to inhibit the functions of the HIV enzyme reverse transcriptase. They stop the reverse transcription process and subsequently HIV replication. Examples of NRTIs are Abacavir, Zidovudine, Emtricitabine, and Lamivudine.
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Similar to NRTIs, NNRTIs target the HIV enzyme reverse transcriptase. However, these two types of Antiretroviral drugs use different mechanisms. NNRTIs attach to reverse transcriptase blocking the reverse transcription process. Dovarivine, Efavirenz, and Nevaparine are examples of NNRTIs.
  • Integrase inhibitors target another HIV enzyme, integrase. They stop the integration of viral DNA with cell DNA and therefore hinder the replication of the virus
  • Protease inhibitors block the functions of the enzyme protease. These drugs ensure that the virus remains in its immature and non-infectious form. They include Atazanavir, Darunavir, and Lopinavir
  • Capsid inhibitors such as Lenacapavir compromise HIV’s capsid, the protein shell that protects the HIV RNA and the enzymes used for replication.
  • Pharmacokinetic enhancers also known as boosters are administered in small doses to increase the efficiency of other ART drugs.

New and Experimental Approaches to HIV Treatment

Antiretroviral Therapy has been instrumental in increasing the life expectancy of people living with HIV. However, this treatment regimen is not a cure.

Researchers are still hard at work in the search for a new HIV drug that can cure the disease. Progress has been slow, but there have been gleams of hope along the way.

As of now, there have been five different cases where it’s said that HIV was cured. The first case is that of Timothy Brown, also famous as the Berlin patient, in 2007. As part of the cancer treatment, doctors performed a stem cell transplant. The donor had a mutation called CCR5-delta 32, which is thought to be able to induce HIV immunity. Brown was “functionally cured” of HIV although he continued to battle cancer complications.

Besides the FDA-approved ART drugs, there are numerous investigational AIDS treatment drugs that are available through clinical trials. They include;

  • Latency reversal agents
  • Microbicides
  • Immune modulators
  • Gp120 attachment inhibitors

HIV researchers are also working on a Therapeutic HIV vaccine. The objective of this vaccine would be to stop the progression of HIV to AIDS, eliminate the need for daily HIV medication, and prevent transmission of the infection.

Other treatment options that are still being studied include;

Stem-cell-based gene therapy

All patients cured of HIV have undergone a stem cell transplant due to other medical complications.

Stem-cell-based gene therapy knows these cases and it utilizes anti-HIV gene-modified hematopoietic stem cells. There is still work to do but if successful, stem cell therapy would generate immune cells consistently throughout the life of a patient.

Broadly neutralizing antibodies

This vaccine would comprise a rare antibody capable of destroying the majority of HIV variants.


The HIV virus features a complex structure. Once the virus comes into the body, it takes numerous stages to replicate and spread across the body. This is known as the HIV life cycle. The incubation period of HIV is one to four weeks.

By understanding this life cycle, researchers have been able to create drugs that can inhibit the different steps. Each class of drugs helps to prevent the virus from progressing to the subsequent stage in the life cycle.

Antiretroviral Therapy is now more advanced than ever and this means that HIV-positive individuals can live long and healthy lives. Of course, you’ll need to take ART drugs faithfully to manage this condition that was once deemed a death sentence. By getting tests and treatment you not only keep yourself safe but also minimize the chance of transmitting the disease.
SFHIV reminds you that prevention is always better than cure.