Title: Why is the combination of three antiretroviral drugs necessary?
Course: Communicable Diseases Part 3 - Ethiopia (Full)

Why is the combination of three antiretroviral drugs necessary?

Combination therapy, in the context of HIV/AIDS, means prescribing three or more ARV drugs to be taken together. Combination therapy is useful for many reasons. Here are the most important ones.

Three or more drugs are needed to stop HIV

Remember that HIV makes new copies of itself very rapidly in infected CD4 lymphocytes. Given time, HIV infection/production escalates out of control, and eventually will result in high levels of viruses in the blood, and low levels of CD4 lymphocytes.

What are the consequences of this for PLHIV?

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They are very likely to develop the opportunistic infections described in Study Session 21.

One drug, by itself, can slow down this fast rate of HIV infection and/or production. Two drugs acting at different points of the virus production cycle can slow it down more, and three drugs together have a very powerful effect. Since ARVs from different drug groups attack the virus in different ways, the standard combination in ART is to use three different ARV drugs.

Combining ARV drugs may overcome or delay drug resistance

Viruses, like bacteria, quickly adapt to their environment, so they can carry on multiplying even when the conditions change for the worse. When a person living with HIV is given ARV drugs for the first time, the environment (in this case, the human body), surrounding the billions of viruses, changes so that it is more difficult for the viruses to multiply. HIV quickly adapts to this new environment by changing its structure in ways that make ARV drugs less effective. The result of this process is that it can go on multiplying even when the drugs are present — this is called drug resistance.

HIV has to make only a single, small change to its structure in order to resist the effects of a particular group of ARV drugs. However, if drugs from more than one group are given in combination, HIV has to make several different changes in its structure in order to resist them all.

It takes longer for HIV to make all the changes necessary for resistance to develop to two drugs, and when three drugs are given together, it takes even longer. This means that giving a combination of three drugs will remain effective in treating HIV infection for a longer period of time than giving just a single drug (or even two).

Note that HIV/AIDS treatment programmes do not randomly prescribe any three ARV drugs. There are strict national guidelines on how to prescribe the different ARV drugs in standard combinations in Ethiopia, as in other countries, as you will see below.