Absence of new thymidine-associated mutations and evidence of an immune virologic response over a 12-month period in a cohort of antiretroviral- experienced HIV-1-infected subjects treated with tenofovir combination therapy [2]

Tenofovir DF (TDF) is a new acyclic nucleotide inhibitor used to treat HIV-infected patients; because of its resistance profile, it is suitable for treating cases of therapeutic failure. Furthermore, it is used on subjects in whom primary HIV infection is attributable to the transmission of resistant strains as well.1 Patients with a high degree of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) present with different mutations in the reverse transcriptase (RT) gene, particularly the thymidine analogue mutations (TAMs) selected after treatment with zidovudine (ZDV) and stavudine (d4T)2-4 or Q151M multidrug resistance (MDR) complex. All these mutations have led to cross-resistance to 6 NRTIs,5 but they have not reduced susceptibility to TDF. To the contrary, mutations like K65R (attributable to therapy with TDF but also selected by abacavir, didanosine, and zalcitabine) and T69S insertions are rare (<2%) in pretreated subjects.6,7 In addition, the M184V mutation that is selected after treatment with lamivudine 8 seems to increase TDF sensitivity, reducing the resistance attributable to the presence of the K65R mutation.9