Tenofovir/abacavir/3TC triple-nuke fails as maintenance regimen

A research letter in the 13 December issue of the Lancet further highlighted the risk of using the triple nucleoside combination of abacavir/3TC/tenofovir, even as a as maintenance therapy. [1]

Serious concern over the potency of this combination led to the issuing of safety warning letters from Gilead and the EMEA last year, following significantly lower rates of viral suppression and higher rates of viral rebound in several studies. [2]

In a retrospective analysis from an observational cohort Hoogewerf and colleagues identified eight patients who had switched to abacavir/3TC/tenofovir and whose viral load was <50 copies/ml from their previous long-term ART (median 14·2 months, range 7·5–67·5). Nine other patients on the same combination were excluded because they had failed a previous combination treatment or because their viral load was already greater than 50 copies/mL at the time of the switch.

Treatment was judged to be failing if the viral load rebounded, confirmed by a subsequent sample. They tested genotype resistance in every patient who failed treatment. Five of the eight patients failed their treatment. The median time to failure was 130 days (range 54-160). The median viral load at the time of failure was just over 3000 copies/mL (range 314-37,597). Three patients are still being treated successfully with the combination after a mean of 199 days. The patients for whom treatment failed differed from those who were treated successfully in baseline viral load before ART (mean 445,000 vs 69,000 copies/mL respectively), baseline CD4 count before ART (mean 88 vs 177 cells/mm3), and in the average time on successful ART before switching (mean 10·8 vs 40·7 months), but too few patients were assessed for the results to be significant.

Genotype resistance at the end of the combination therapy in all five patients who failed treatment showed one patient had an M184I mutation, one a K65R mutation, one an M184V and a K65N mutation, and one a M184V and a K65R mutation. One patient did not have any of these mutations.

The authors conclude: “HIV-infected patients should not be given the abacavir, lamivudine, and tenofovir combination either as initial treatment in treatment-naïve patients, or as alternative treatments for successful ART regimens.”