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Why are combinations of antiretroviral drugs used to treat HIV?

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AIDS Scanning electron micrograph of HIV-1 virions (green) budding from a cultured lymphocyte. Multiple round bumps on the cell surface represent sites of virion assembly and budding.

Combinations of antiretroviral drugs are used to treat HIV primarily because the virus replicates at a very high rate, creating frequent opportunities for mutation and the rapid emergence of drug-resistant strains. When a single antiretroviral drug is used, HIV can quickly develop resistance, rendering the treatment ineffective.1234

By using a combination of drugs—a strategy known as highly active antiretroviral therapy (HAART)—physicians can target the virus at different stages of its life cycle. For example, combining reverse transcriptase inhibitors with protease inhibitors suppresses viral replication more effectively than any single agent alone. This multi-pronged approach not only provides superior suppression of the virus but also significantly slows the emergence of resistant viral variants.132

Because the virus can persist in latent reservoirs within the body, patients must strictly adhere to their prescribed combination regimen to prevent viral rebound and the development of resistance. If a regimen fails, resistance testing is used to tailor a new, more intensive "salvage" regimen.1