However, neither the K103N nor the M184V
mutation was detected in any of those 222 clones, but both mutations were rapidly selected during early treatment failure.
10] decline in plasma HIV-RNA and selection of M184V
in HIV .
by itself causes high-level (>100-fold) resistance to lamivudine and emtricitabine.
The addition of 3TC (or FTC) is recommended as the M184V
mutation that it selects for impairs viral replication.
Those findings suggest maintaining M184V
has no virologic or immunologic value in people taking antiretrovirals.
AVX-201 is a randomised, double-blind study of two doses of ATC compared to lamivudine (3TC) in treatment-experienced HIV-1-infected patients with the M184V
5%) had resistance to NRTIs (Figure) due to the mutations M184V
(15 patients), M184I (1), T215Y (1), T215F (3), K65R (2), and Q151M (1); thymidine analog mutations M41L (2), D67N (2), K70R (3), K219Q (1), and K219E (1) were also detected.
Resistance testing showed that all 20 patients had developed an M184V
mutation and half had a K65R mutation.
There were different theories of why these three-drug regimens failed, but now it is widely believed that the main problem is that they did not provide a high enough genetic barrier to the development of two viral mutations, K65R and M184V
, which led to resistance to the drugs.
At the Ninth International Congress on Drug Therapy in HIV Infection, the company presented the 48-Week Data from Study AVX-201 -- A Randomised Phase IIb Study of Apricitabine (ATC) in Treatment-Experienced Patients with M184V
and Nucleoside Reverse Transcriptase Inhibitors (NRTI) Resistance.
ABC should only be used for first line (without genotyping) since >3 TAMS + M184V
confers high level cross-resistance to ABC.
So for example I think we've come to believe--whether it's true or not (2-4)--that using lamivudine or emtricitabine in a regimen to maintain the M184V
mutation is probably of some virologic benefit.