Do some drugs develop resistance more easily than others?

Some drugs will stop working after only one mutation. This is the case with NNRTIs and some nukes (3TC and FTC) and lenacapavir (a capsid inhibitor). Integrase inhibitors can also easily develop resistance. See Figure 4.

These drugs are more vulnerable when viral load is above 50 copies/mL.

These mutations can stop similar drugs in the same class from working. This is called cross-resistance.

Protease inhibitors and some other nukes develop resistance more slowly.

The first mutations does not make much difference. But as resistance develops these drugs also stop working. See Figure 5. These drugs take longer to develop cross-resistance.

Integrase inhibitors are perhaps more similar to NNRTIs. If resistance mutations develop, cross resistance can also develop quite quickly.

Figure 4: How one mutation can stop some drugs working

Graph showing 1 mutation causing extensive resistance.

Some drugs stop working after only one mutation.

These include NNRTIs (nevirapine, efavirenz, rilpivirine and etravirine), integrase inhibitors (raltegravir, dolutegravir, bictegravir and cabotegravir) and some nukes (3TC  and FTC).

Figure 5: Resistance increases slowly with some drugs

Graph showing number of mutations increasing from 1 (low resistance) to 6(extensive resistance)

With other drugs, the first one or two mutations make little difference.

If you continue taking the same drug, more mutations develop. The drugs work less well with every step. PIs and some nukes work this way.

Last updated: 1 January 2025.