Understanding Retroviruses
A retrovirus is a unique type of virus that carries its genetic information in the form of RNA, rather than DNA [1.9.1]. When a retrovirus like Human Immunodeficiency Virus (HIV) infects a cell, it uses a special enzyme called reverse transcriptase to convert its RNA into DNA [1.9.2]. This viral DNA is then inserted into the host cell's own DNA, effectively hijacking the cell's machinery to produce more copies of the virus [1.9.4]. Antiretroviral drugs are specifically designed to interfere with this life cycle.
How Do Antiretroviral Drugs Work?
Antiretroviral drugs do not cure HIV, but they suppress its replication [1.2.5]. By doing so, they reduce the amount of HIV in the body, known as the viral load [1.2.3]. This gives the immune system, particularly the CD4 cells that HIV targets, a chance to recover and strengthen [1.2.3]. The primary goal of treatment is to reduce the viral load to an undetectable level, which means the amount of HIV in the blood is so low it can't be measured by standard tests [1.2.1]. People who maintain an undetectable viral load can live long, healthy lives and have effectively no risk of transmitting HIV to their sexual partners [1.4.2].
To achieve this, multiple drugs are used together in a regimen known as Antiretroviral Therapy (ART) [1.2.1]. Using a combination of drugs from different classes makes the treatment more powerful and reduces the likelihood of the virus developing resistance [1.2.5].
The Main Classes of Antiretroviral Drugs
There are several classes of antiretroviral drugs, each targeting a different stage of the HIV life cycle [1.10.1, 1.3.5]:
- Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs): These were some of the first HIV drugs developed. They act as faulty building blocks, tricking the reverse transcriptase enzyme and terminating the DNA-building process [1.2.1, 1.10.2].
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Instead of providing faulty materials, NNRTIs bind directly to the reverse transcriptase enzyme itself, preventing it from functioning [1.2.1, 1.10.2].
- Protease Inhibitors (PIs): After new HIV genetic material is created, it needs an enzyme called protease to cut long protein strands into smaller, functional pieces to assemble new, mature viruses [1.2.5]. PIs block this enzyme, resulting in the production of immature, non-infectious virus particles [1.10.2].
- Integrase Strand Transfer Inhibitors (INSTIs): This class of drugs blocks the integrase enzyme, which is responsible for inserting the viral DNA into the host cell's DNA [1.3.5, 1.10.2]. Without this step, the virus cannot take over the cell to replicate.
- Entry Inhibitors: This is a broader category of drugs that prevent HIV from entering the CD4 cells in the first place. They include:
- Attachment inhibitors: Block HIV from binding to the CD4 receptor on the cell surface [1.3.5].
- Post-attachment inhibitors: Prevent changes needed for the virus to enter the cell after it has already bound to the receptor [1.3.5].
- CCR5 antagonists: Block a specific co-receptor (CCR5) on the surface of some immune cells that HIV uses to gain entry [1.3.5].
- Fusion inhibitors: Interfere with the virus's ability to fuse its outer membrane with the host cell's membrane [1.3.5].
- Capsid Inhibitors: A newer class of drugs that interfere with the HIV capsid, a protein shell that protects the virus's genetic material and enzymes needed for replication [1.3.5].
- Pharmacokinetic Enhancers (Boosters): These are not antiretrovirals themselves but are used to 'boost' the effectiveness of other drugs, typically protease inhibitors. They slow down the breakdown of the primary drug in the body, allowing it to remain at a therapeutic level for longer [1.2.1].
| Drug Class | Mechanism of Action | Stage of HIV Life Cycle Targeted [1.10.1] |
|---|---|---|
| NRTIs | Provide faulty DNA building blocks to stop DNA synthesis. | Reverse Transcription |
| NNRTIs | Bind to and inhibit the reverse transcriptase enzyme. | Reverse Transcription |
| Protease Inhibitors (PIs) | Block the protease enzyme from maturing new virus particles. | Budding & Maturation |
| Integrase Inhibitors (INSTIs) | Prevent viral DNA from being integrated into the host cell's DNA. | Integration |
| Entry Inhibitors | Block the virus from binding to, fusing with, or entering the host cell. | Binding & Fusion |
| Capsid Inhibitors | Disrupt the protective protein shell of the virus. | Assembly |
Common Side Effects
While modern antiretroviral drugs are much better tolerated than older versions, they can still cause side effects. Many are mild and may lessen over time, such as nausea, diarrhea, fatigue, and headache [1.5.2]. However, some drugs can have more significant or long-term effects, including high cholesterol, weight gain, bone loss, and potential damage to the kidneys or liver [1.5.3, 1.5.4]. It is crucial for patients to communicate with their healthcare provider about any side effects they experience [1.4.2].
The Challenge of Drug Resistance
HIV can mutate, creating variations that are not affected by a specific drug. This is known as drug resistance [1.7.4]. Resistance often develops when a person does not take their ART regimen consistently, allowing the virus to replicate in the presence of low drug levels [1.7.2, 1.7.3]. This is why strict adherence to the prescribed medication schedule is vital. Combination therapy with at least two, and preferably three, fully active drugs is the standard approach to prevent resistance [1.7.1, 1.2.5].
Antiretrovirals for Prevention: PrEP and PEP
Antiretroviral drugs are also highly effective at preventing HIV infection.
- Pre-Exposure Prophylaxis (PrEP): This involves people who are at risk for HIV taking specific antiretroviral medication on an ongoing basis (daily as a pill or as an injection every few months) to prevent infection [1.8.1]. When taken consistently, PrEP reduces the risk of getting HIV from sex by about 99% [1.8.1].
- Post-Exposure Prophylaxis (PEP): PEP is an emergency measure. It involves taking a 28-day course of antiretrovirals after a potential exposure to HIV [1.8.2]. To be effective, PEP must be started within 72 hours of the exposure [1.8.2].
The Future of Antiretroviral Therapy
Research continues to advance HIV treatment. The focus is on developing longer-acting therapies to improve convenience and adherence, such as injections given every one, two, or even six months [1.11.2, 1.11.4]. In July 2025, the World Health Organization recommended injectable lenacapavir, which is administered just twice a year, for HIV prevention [1.11.1]. Researchers are also working on new drug classes and therapies for individuals with resistance to multiple existing drugs [1.11.2, 1.11.3].
Conclusion
Antiretroviral drugs have fundamentally changed the course of the HIV epidemic. By effectively suppressing viral replication, ART allows people with HIV to live long, healthy lives and prevents the further spread of the virus [1.2.3]. From complex daily regimens to emerging long-acting injectables, the evolution of these life-saving medications represents one of the greatest successes in modern medicine. Continuous research, combined with improved access to treatment and prevention, offers hope for controlling and eventually ending the HIV epidemic.
For further authoritative information, you can visit the NIH's HIVinfo page on HIV Treatment. [1.2.3]
