What Is Antiretroviral Therapy?

Overview

Antiretroviral therapy (ART) is a treatment strategy designed for managing human immunodeficiency virus (HIV) infection. This therapy involves the use of a combination of medicines, known as antiretroviral drugs, to suppress the virus and slow or prevent the progression of HIV. HIV is a retrovirus, meaning that it invades your cells and uses their own machinery to create new copies of the virus and spread throughout your body. ART works by suppressing the replication of the retrovirus within your body, thus why the treatment is called “antiretroviral therapy”.

There is currently no cure for HIV. Once you get infected, your body cannot get rid of this disease, and it progresses to acquired immune deficiency syndrome (AIDS) over time. This stage of the disease causes severe suppression of your immune system and people with AIDS are affected by many life-threatening illnesses. The primary goal of ART is to prevent this progression from HIV to AIDS, protect your immune system and reduce the risk of severe disease complications. The World Health Organisation (WHO) recommends offering ART to all patients diagnosed with HIV. With early and continued treatment, many HIV patients live normal lives unaffected by this previously devastating disease.

You might hear antiretroviral therapy referred to as ART, combined antiretroviral therapy (cART), or highly active antiretroviral therapy (HAART) - they are all different names for the same treatment strategy.

What is HIV and AIDS?

Human immunodeficiency virus (HIV) is a virus that attacks the immune system, specifically your CD4 T-cells (also called helper T-cells). These are a type of white blood cell that plays an important role in organising your body’s defence against infections. The virus gradually weakens your immune system, reducing your capability to fight everyday infections and diseases. Over time, if untreated, HIV can progress to acquired immune deficiency syndrome (AIDS). This is a stage characterised by potentially life-threatening infections and illnesses that occur when your immune system has been severely damaged by HIV.

The transmission of HIV occurs through the exchange of certain body fluids, such as blood, sexual fluids, and breast milk. Once inside the body, the virus infiltrates into your CD4 cells and uses them as hosts for replication to produce many copies of themselves. HIV is a retrovirus, which means it uses its own RNA (its genetic instructions) as a template to make DNA (the genetic instruction found inside every one of your cells). This replication process involves many different stages and results in the destruction of the CD4 cell used as a host, leading to a gradual decline in the number of functional CD4 cells in your body. As your CD4 cell count drops and your immune system weakens, the risk of progression to AIDS and developing life-threatening illnesses increases.¹

Given the severity of HIV/AIDS and its impact on the immune system, effective treatment strategies like ART are essential for managing the disease and improving patient outcomes. There is currently no cure for HIV/AIDS, but treatment strategies such as ART can control the virus and prevent progression of the HIV to AIDS. With early diagnosis and this effective treatment, most people with HIV will not develop any AIDS-related illnesses and can live long and healthy lives.

How does antiretroviral therapy work?

ART works by stopping the virus from replicating inside your body. This allows your immune system to repair itself and prevent any further damage. The goal of this treatment is to have an undetectable viral load - this means that the level of HIV in your body is low enough to not be detected by a test.

ART uses a combination of different antiretroviral (ARV) drugs, normally in the form of tablets or a single combined tablet, which needs to be taken every day. Each ARV drug stops HIV at a different part of its replication process (how the virus makes copies of itself) and can be classified into different types based on which stage of the process it inhibits. Usually, ART involves 3 drugs from at least two different classes, termed a “triple cocktail”. There are 5 main classes of drugs used to treat HIV infection:²

• Entry inhibitors: These drugs block the entry of HIV into your CD4 cells. Without getting into your cells in the first place, the virus cannot replicate and spread throughout your body. Examples of entry inhibitor drugs include maraviroc, enfuvirtide, and ibalizumab.³
• Nucleoside reverse-transcriptase inhibitors (NRTIs): NRTIs inhibit the process of reverse transcription. After HIV enters your CD4 cells, it makes copies of itself by first converting its RNA (the virus’ genetic information) into DNA in order to integrate into your DNA which is kept inside your cells. This process is called reverse transcription and requires an enzyme called reverse transcriptase. NRTIs work to stop this process by inhibiting the reverse transcriptase enzyme. Examples of this drug include zidovudine, abacavir, lamivudine, and emtricitabine.⁴
• Non-nucleoside reverse-transcriptase inhibitors (NNRTIs): NNRTIs prevent the process of reverse transcription by inhibiting the reverse transcriptase enzyme through a slightly different mechanism to NRTIs. Examples of NNRTIs include nevirapine, efavirenz, etravirine, and rilpivirine.⁵
• Integrase inhibitors: These drugs work by disabling an enzyme called integrase which is required for HIV to integrate its converted viral DNA into the human DNA in your CD4 cells. Examples of this drug include elvitegravir, dolutegravir, and bictegravir.⁶
• Protease inhibitors (PIs): PIs inhibit HIV protease, an enzyme required by newly formed (immature) HIV to become a mature virus that can go on to infect your other CD4 cells and spread throughout the body. Examples include indinavir, nelfinavir, atazanavir, and darunavir.⁷

Your healthcare provider should refer you to a specialist who is trained in treating HIV. This specialist will help determine which combination of ARV drugs and ART will work best for you. 

What is the outlook of antiretroviral therapy?

Your healthcare provider will monitor your viral load and CD4 cell counts to determine your response to ART. Initially, you will be checked every 4-8 weeks after starting ART until you reach an undetectable viral load, then every 3-6 months after this. Your healthcare provider will check:

• Viral load: This measures the amount of virus in your blood. The goal of the treatment is to have an undetectable viral load. This doesn’t mean that the HIV is totally gone as it could still be present in other places in your body and could spread if treatment is stopped. However, it does mean that the virus is currently controlled and cannot be passed on to others.
• CD4 cell count: CD4 T-cells are white blood cells that are progressively targeted and destroyed by HIV. Levels above 500 cells per mm³ of blood are categorised as normal, between 200 - 499 cells per mm³ is immunosuppressed, and below 200 cells per mm³ is typically when HIV progresses to AIDS. With early ART, your CD4 count should gradually increase to normal or near-normal levels.⁸ 

When taken correctly and consistently, ART is very successful. While ART cannot cure HIV, it can reduce your viral load to undetectable levels. ART works to reduce HIV levels within 6 months, and over 90% of people have undetectable levels of HIV in their blood within 12 months. Having an undetectable viral load is important:⁹

• This can keep your immune system healthy and reduce the risk of progressing to AIDS and developing life-threatening illnesses.
• Most people who start ART soon after their diagnosis and continue to take it consistently can expect to live as long as someone without HIV. 
• Sustaining an undetectable viral load reduces the risk of passing HIV to another person via sex to zero: “undetectable = untransmittable”.

It is extremely important that you take your medications as prescribed, without missing or skipping any doses in order for ART to be successful.

What are the side effects and complications of antiretroviral therapy?

Side effects

The side effects of ART typically depend on which combination of medications you are taking. Common side effects might include:

• Nausea
• Vomiting and diarrhoea
• Headache
• Fatigue (tiredness)
• Insomnia (difficulty sleeping)
• Mood changes or depression
• Mild rash

Most of these side effects are temporary and usually resolve by themselves within a few weeks of starting ART as your body gets used to the medications you're taking. 

Complications

Some side effects of ART can be more severe and have long-term consequences. For example, certain ARV medications can cause high cholesterol which increases the risk of developing heart disease, the leading cause of death worldwide.

Another very serious complication of ART is drug resistance. HIV has a short life cycle and can mutate rapidly. This means that there is a high risk of developing resistance to ARV drugs if they are not taken correctly - for example, if you do not take your medication regularly as prescribed. This can be very serious as you will not be able to use that combination of treatment again. If you continue to develop resistance to different drug combinations, ART might no longer be an effective treatment and your disease will worsen. 

FAQs

When should I start antiretroviral therapy? 

Antiretroviral therapy should be started as soon as possible after a diagnosis of HIV. Early treatment is very important, even if you feel healthy, as HIV progressively damages your immune system. This will give you the best chance of maintaining a strong immune system and living a healthy life.

How long do I need to be on antiretroviral therapy?

You will need to be on antiretroviral therapy for your whole life. It is really important that you take these medications every day as prescribed and do not miss any doses. Even if you have an undetectable viral load, this doesn’t mean that the virus is gone - if you stop taking your antiretroviral drugs, the virus can spread throughout your body and affect your health.

How long will I live on antiretroviral therapy?

With early and continued treatment, people with HIV taking antiretroviral therapy can expect to live as long as people who don't have HIV. 

Summary

In summary, antiretroviral therapy (ART) is a HIV treatment which involves the use of a combination of different antiretroviral drugs to stop the virus from replicating and spreading throughout your body. ART stands as a cornerstone in the management of HIV/AIDS, providing individuals with an effective means to control the virus, maintain their health, and reduce the risk of transmission to others. Treatment should be started as soon after diagnosis as possible to prevent further damage to your immune system, and it is vital that the medication is taken regularly as prescribed for your entire life. With these factors in place, many people diagnosed with HIV can expect to live a long and healthy life, highlighting the transformative impact of ART in the ongoing battle against HIV/AIDS.