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What Is Combination Antiretroviral Therapy?

By Glyn Sinclair
Updated: May 17, 2024

Combination antiretroviral therapy is the use of several antiretroviral drugs taken in combination by a patient as a method to combat diseases and retroviruses such as Human Immunodeficiency Virus (HIV). A retrovirus is a ribonucleic acid (RNA) virus and is able to inject a deoxyribonucleic acid (DNA) copy of its hereditary information into the cells as a method of replicating itself. There are several classes of antiretroviral drugs, or "antiretrovirals." When taken in combination they can inhibit the life-cycle of the retrovirus. Although side effects are common during combination antiretroviral therapy, the patient is typically required to adhere to a strict regimen over a long period of time for the drugs to be effective.

When used in combination, the drugs basically put up multiple barriers to the virus’s ability to replicate. The theory behind combination drug therapy is the hope that if resistance to one of the drugs arises, then the other drugs will serve to combat the resistance. Usually three drugs are used in combination: a protease inhibitor and two nucleoside-analog Reverse-Transcriptase Inhibitors (RTIs). This is sometimes referred to as the triple cocktail. There have been very few, if any, cases of successful suppression of HIV virus when just one single drug has been employed.

There a number of adverse effects that can be experienced during combination antiretroviral therapy. These vary due to factors like ethnicity and negative interactions with other medications. The side effects can include nausea, hepatitis, jaundice and liver failure, among others. The drugs can have severe side effects for those in which the disease is already advanced. Other concerns include patients that develop resistance due to continually missing doses, as well as cost, with the majority of the affected population unable to afford the drugs.

Due to the potential toxicity of combination antiretroviral therapy, an intermittent therapy, or “break” from the drug was sometimes attempted in past patients. This program was designed to give the patient a break from sustained exposure to the drugs and involved discontinuing the drugs for a few days and then reinstating them. In one study, 5,000 infected patients were followed up after 16 months and those that received intermittent therapy had higher rates of opportunistic diseases and death compared to those that were kept on sustained combination antiretroviral therapy. Some of the issues associated with the intermittent therapy included cardiovascular, liver and kidney problems. The program was eventually discontinued as it was considered a failure and thought to actually create drug resistance in patients.

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