Changing drugs and drug classes

Choosing a subsequent antiretroviral regimen after virological failure involves either adding extra drugs (treatment intensification) or replacing existing drugs with others that might be expected to work better.

NRTI backbone combinations are most commonly changed due to side-effects or drug resistance. Decisions about whether to substitute a protease inhibitor (PI) for a NNRTI, or vice versa, will largely depend on treatment history and drug resistance.

If a person has experienced virological failure while taking either efavirenz or nevirapine, both NNRTIs are unlikely to be effective due to cross-resistance. A protease inhibitor will probably be a better choice. Etravirine, the first new NNRTI to be approved in a decade, may also be an effective option, depending on baseline resistance mutations. 

After failure on an NNRTI-based regimen, a reasonable change is to one with a boosted PI. If lipid profile is a concern, raltegravir may be a good choice.1 

Boosted PIs have a higher genetic barrier to resistance than unboosted PIs and may provide longer-lasting viral suppression. After treatment failure with a PI-based therapy, one option is to switch to a boosted-PI regimen supported by two NRTIs chosen after resistance testing. One study has shown that with existing PI mutations, boosted darunavir is more effective than lopinavir/ritonavir.2

Studies have shown that changing to regimens that contain T-20, maraviroc, or raltegravir can dramatically improve the likelihood of achieving viral suppression, especially when they are combined with a boosted PI and/or etravirine.  


  1. Markowitz M et al. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr 46(2):125-33, 2007
  2. De Meyer SM et al. Efficacy of once-daily darunavir/ritonavir 800/100 mg in HIV-infected, treatment-experienced patients with no baseline resistance-associated mutations to darunavir. J Acquir Immune Defic Syndr 49(2): 179-182, 2008
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.