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HIV, a virus that attacks the immune system, was once a fearsome disease that could be interpreted as a death sentence. Because of the nature of the virus, when people are infected with HIV, they are infected for life. Despite the permanence of HIV, it has become increasingly treatable with medications.

While NRTIs (nucleoside reverse transcriptase inhibitors) were the first type of drug made available for HIV treatment, there are now six classes of approved HIV medications. Most of these drugs treat HIV by inhibiting specific enzymes that allow the virus to spread. Two of these drug classes, protease inhibitors and integrase inhibitors, target the protease and integrase enzymes, respectively.

 Graphic representation of a protease enzyme.

Image Source: Laguna Design

Protease enzymes cut and break down proteins. Though they are present in the HIV virus, protease enzymes are not always harmful; for example, we have protease enzymes that help us digest our food. The HIV protease enzyme cuts HIV proteins at specific locations to create the building blocks needed for the virus to spread. To decrease the replication of the HIV virus, protease inhibitors mimic viral proteins and bind to the protease enzyme, preventing it from cutting its own proteins. Because HIV cannot use proteins if they are not separated correctly, viruses with uncut protein chains are successfully rendered ineffective.

Integrase enzymes, as may be suggested by their name, help integrate retroviral DNA into the infected host’s DNA. Integrase enzymes are important to the HIV virus because they allow HIV to replicate itself using the cells of the host organism it has infected. Integrase inhibitors prevent the replication of the HIV virus by stopping integrase from binding to the host DNA, therefore blocking the insertion of the viral DNA that the virus needs to do to survive.

 HIV DNA is integrated into the host DNA to be replicated.

Image Source: Laguna Design

In the grand scheme of HIV treatment, protease inhibitors and integrase inhibitors are quite different. Protease inhibitors have been around for a while, while integrase inhibitors have been approved for less than a decade. Rather than being taken together for HIV treatment, recommended initial regimens suggest taking one or the other, along with NRTIs. At this time, neither one is considered superior to the other, though some studies speculate that integrase inhibitors may be more effective. Regardless, both protease inhibitors and integrase inhibitors are important options for HIV treatment, and they can both improve virus suppression.

Featured Image Source: Diagram of the HIV virion by Thomas Splettstoesser

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