2023 Treatment Guide: HIV Drug Classes

HIV has bedeviled scientists for over 40 years. One of the reasons HIV has been so hard to cure is that it’s a retrovirus. This means it contains single-stranded RNA (ribonucleic acid) instead of the typical double-stranded DNA that human cells carry. Retroviruses also carry an enzyme called “reverse transcriptase,” which allows it to copy RNA into DNA — and then use that DNA copy to invade human cells.

Fortunately scientists developed antiretroviral drugs three decades ago that were able to prevent HIV from replicating in the human body. This breakthrough was huge, changing HIV from an often fatal disease to a manageable chronic condition. Since then, HIV drugs have only grown more effective and less toxic.

HIV treatment regimens include drugs from multiple classes to improve their combined effectiveness, decrease toxicity, and help prevent the development of drug resistance. Here’s brief descriptions of these classes and how they work.

BROADLY NEUTRALIZING ANTIBODIES (bNAbs)

Drugs in this class are antibodies that can recognize and block HIV or activate other immune cells to help destroy the virus. Some hold potential to treat HIV without other medications.

CCR5 ANTAGONISTS (CAs)

Drugs in this class block the CCR5 coreceptor on the surface of CD4 cells preventing HIV from binding and entering the cells.

CAPSID INHIBITORS (CIs)

Meds in this class help inhibit the proteins that protect HIV’s genetic material. In Dececember, Gilead Sciences’ injectable Sunlenca (lenacapavir) became the first and only approved capsid inhibitor-based HIV treatment option. Taken in combination with other antiretrovirals, lenacapavir is prescribed for adults with multi-drug resistant HIV.

ENTRY AND FUSION INHIBITORS (EIs and FIs)

Drugs in this class help block HIV from binding, fusing, and entering T cells. They are always taken with other HIV medication.

INTEGRASE STRAND TRANSFER INHIBITORS (INSTIs)

Drugs in this class block integrase, an enzyme HIV needs in order to reproduce. HIV uses integrase to insert its viral DNA into the DNA of T cells. Blocking the integration process prevents HIV from replicating. They are always taken with other HIV medication.

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs, also known as nukes)

Drugs in this class block reverse transcriptase, an enzyme that HIV needs in order to reproduce. HIV uses reverse transcriptase to convert its RNA into DNA; blocking the process prevents HIV from replicating. They are always taken with at least one other HIV med.

NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs, also known as nonnukes)

Drugs in this class also block reverse transcriptase, as NRTIs do, but in a different way. They are always taken with at least one other HIV medication.

NUCLEOSIDE REVERSE TRANSCRIPTASE TRANSLOCATION INHIBITORS (NRTTIs)

Drugs in this class also block reverse transcriptase but do so by preventing translocation of an enzyme. They are always taken with other HIV medication.

PHARMACOKINETIC ENHANCER/CYP3A INHIBITORS (PKEs, also known as boosters)

Drugs in this class boost the effectiveness of antiretroviral medication. When the two are taken together, the pharmacokinetic enhancer slows the breakdown of the other drug, which allows the drug to remain in the body longer at a higher concentration. They are always taken with other HIV medication.

POST-ATTACHMENT INHIBITORS (PAIs)

Drugs in this class bind to CD4 cells after HIV has attached to them but still inhibit the virus from infecting those cells. They are always taken with other HIV medications.

PROTEASE INHIBITORS (PIs)

Drugs in this class block activation of protease, an enzyme HIV needs to develop. Blocking protease prevents immature forms of HIV from becoming a mature virus capable of infecting other T cells. They are always taken with other HIV medication.

SINGLE-TABLET REGIMENS (STRs)

Drugs in this category are fixed-dose pills that combine multiple anti-HIV medications (often from more than one class of drug) into a single tablet, which is usually taken just once a day. They do not need to be taken with other HIV medication.

TOLL-LIKE RECEPTORS (TLR)

Drugs in this class stimulate the immune system’s T cells, activating a more robust response to the viral invader. They are always taken with other HIV medications.