As with all other anti-HIV drugs, strains of HIV that are resistant to tenofovir (Viread) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug .

Tenofovir does not appear to select new resistance mutations in the vast majority of people who add the drug to a failing regimen. Genotypic analysis from the 907 study found that only 3% of the patients with detectable viral load had developed a K65R mutation, which has been associated with tenofovir resistance in test-tube studies.1 2 3 4

The 902 and 907 studies, in which some participants have taken tenofovir for up to 48 weeks, showed that some resistance mutations in the reverse transcriptase gene did not undermine the activity of tenofovir, including D67N, K70R, T215Y/F and K219Q/E/N. However, the thymidine analogue mutations (TAMs) M41L and L210W did reduce the response to tenofovir in these studies.3

Tenofovir is also active against virus with the ddI (didanosine, Videx / VidexEC) resistance mutation L74V and the ddC (zalcitabine, Hivid) resistance mutation T69D. In addition, laboratory studies suggest that virus which is resistant to NRTIs with the Q151M multidrug resistant mutation will still be sensitive to tenofovir. Multi-NRTI resistant virus with a T69S double insertion mutation may exhibit reduced susceptibility to tenofovir, although it may remain sensitive to tenofovir if the M184V mutation, which is associated with prior 3TC (lamivudine, Epivir) treatment, is also present.5 In general, the presence of the M184V mutation in the context of other drug resistance mutations seems to improve sensitivity to tenofovir.4

This has led some researchers to suggest that it may be appropriate to maintain 3TC or abacavir (Ziagen) treatment in treatment-experienced people commencing tenofovir in order to preserve this mutation. Furthermore, tenofovir seems to have a high barrier to resistance as well as being effective against HIV with NRTI resistance, making it an attractive candidate for first- and second-line treatment.


  1. Squires K et al. Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial. Ann Intern Med 139: 313-320, 2003
  2. McColl D et al. Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. J Acquir Immune Defic Syndr 37: 1340-1350, 2004
  3. Miller MD et al. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. J Infect Dis 189: 837-846, 2004
  4. Wainberg MA et al. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir Ther 4: 87-94, 1999
  5. Miller MD et al. Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples. Nucleosides Nucleotides Nucleic Acids 20: 1025-1028, 2001
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.