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Salvage therapy with abacavir in HIV-1-infected patients with previously
documented M184V mutation: a possibility of NRTI recycling
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Antivir Ther. 2003 Apr;8(2):121-6.
Maggiolo F, Callegaro A, Arici C, Quinzan G, Gregis G, Ripamonti D, Tebaldi
A, Goglio A, Suter F.
Division of Infectious Diseases, Ospedali Riuniti, Bergamo, Italy.
We evaluated in an open-label, randomized, controlled, pilot trial if the
re-emergence of previously selected resistant strains, harbouring M184V mutation,
could be modulated by the use of different drug associations as components of
the new antiretroviral regimens. In addition, we assessed the clinical
relevance of this mutation on the management of heavily pretreated HIV-infected
patients. The primary end-point of the study was the reselection of M184V
mutation. Secondary end-points were the variation over time of HIV RNA plasma levels
and CD4 cell counts and the progression of HIV disease.
The primary population for efficacy analysis was the intention-to-treat
exposed population. After a run-in phase consisting in a new treatment regimen
excluding either lamivudine (3TC) or abacavir (ABC) so as to clear the previously
documented M184V mutation, 18 patients with an HIV RNA plasma level greater
than 10000 copies/ml were randomized to receive an antiretroviral drug regimen
(at least three drugs) including either ABC or the association of ABC+3TC. All
patients were naive to ABC.
The M184V mutation reappeared in 1/9 patients in the ABC group and in 8/9
patients in the ABC+3TC group (P<0.003, 95% CI: 0.5-1). In the ABC group we
observed a rapid decrement of viral load that was maintained throughout all the
study period (P<0.05). On the contrary, in the ABC+3TC group, after a transient
decrement at 2 months, a progressive increment towards baseline values was
observed. The proportion of patients with a viral load reduction of at least 0.5
logs at 12 months was significantly higher in the ABC group: 8/9 patients vs
3/9 (P=0.05, 95% CI: 0.2-0.92).
Similarly, from an immunological point-of-view, the increase at all time
points (since randomization) in CD4 cell count was statistically significant in
the ABC group (P<0.01), while no difference was observed in the ABC+3TC group.
The possibility of a successful use of ABC in salvage regimens opens
alternative therapeutic options for heavily pretreated patients with previously
documented M184V mutation. Further studies should clarify whether this is true for
other drugs of the nucleoside analogues class.
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