Mutations that cause drug resistance generally only develop on ART when your viral load is detectable. If your viral load is still above 500 copies/mL after 2-3 months, or above 50 copies/mL after 6 months, you can develop resistance.
What Happens if My Viral Load Becomes Detectable Again?
If your viral load becomes detectable, the viral load test needs to be repeated within 2-4 weeks of the first blood sample. Often this is a laboratory or test error. Small increases that go back down again are called "blips". The second test will help find out what is happening.
If the combination is failing it is good to confirm this early. You will get a better response to a second treatment if you change when viral load levels are still low. See the i-Base Guide to Changing Treatment and Drug Resistance for more information.
The best way to avoid resistance is to take your drugs every day and on time. Avoiding resistance is more important than increasing your CD4 count because it will let your treatment work for many years. Having an undetectable viral load (less than 50 copies/mL) dramatically reduces the risk of resistance.
Cross-resistance is when a drug mutation against one drug causes other similar drugs to fail, even if you have never taken them before. This is particularly true of drugs in the same class. So if you develop resistance to one NNRTI such as rilpivirine then efavirenz (another NNRTI) is unlikely to work.