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Cross-resistance by drug class

There are many types (or classes) of drugs. Each one works at different stages of the HIV life cycle.

NRTIs

Cross-resistance between NRTIs is complex. Some drugs are active even with some resistance.

NNRTIs

There is strong cross-resistance between early NNRTIs such as nevirapine and efavirenz.

Second-generation NNRTIs like etravirine, rilpvirine and doravirine can sometimes overcome early drug resistance.

This needs advice from a resistance specialist.

Protease inhibitors (PIs)

There is strong cross-resistance between some PIs.

Some PIs, including darunavir/r and tipranavir/r, can work against early PI resistance.

Darunavir/r is sometimes used twice-daily tto overcome drug resistance.

Integrase inhibitors

As a new class, integrase inhibitors work if you have resistance to other drug classes. But they can also have cross-resistance within the class.

Resistance to raltegravir or elvitegravir can sometimes be overcome by using a higher dose of dolutegravir (50 mg twice a day).

Dolutegravir and bictegravir have stronger barrier to drug resistance than other integrase inhibitors.

Entry inhibitors

Several different type of types are entry inhibitors. Drugs that work in differenet ways ddo not have cross resistance. These include:

  • maraviroc (working against CCR5). Rarely used.
  • enfuvirtide (T-20) (fusion inhibitor. No longer used.
  • ibalizumab (Trogarzo) (monoclonal antibody that blocks CD4 attachment). Approved in the EU in 2019 as a new option to treat drug resistant HIV. Given as an infusion every two weeks.
  • fostemsavir (Rukobia) (gp-120 inhibitor). Approved in the EU in January 2021 as a new option to treat drug resistant HIV. An oral tablet taken twice-daily.

Capsid inhibitors

Capsid inhibitors work at several stages of the HIV lifecycle. Currently lenacapavir is the only capsid inhibitor approved as a treatment. This drug is being used at all stages of infection, including with extensive drug resistance. It will not be cross resistant to any other HIV drug.

Lenacapavir is only approved for people with extensive drug resistance. It is given as an injection every 6 months.

Maturation inhibitors

This is a class that works at the late stages of the HIV lifecycle. Drugs in this class are only at a research stage. These drugs will not be cross resistance to other types of HIV drugs.

Links to more information

Last updated: 1 January 2025.