Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation

The effect of the HIV reverse transcriptase K65R mutation on virological response to salvage therapy has not been clearly defined.

From six Italian clinical centres, all consecutive patients starting salvage antiretroviral therapy after virological failure in the presence of the K65R mutation identified by a genotypic resistance test were selected.

Among 145 subjects included over a 197 person-year follow-up, the estimated probability of virological response (VR, defined as reaching HIV RNA < 50 copies/ml after salvage therapy) at 24 and 48 weeks was 36% and 60%, respectively. The strongest independent predictor of VR was the inclusion of a thymidine analogue (TA) in the salvage regimen. The presence of M184V and the introduction of lopinavir/ritonavir as new drug were both marginally associated with better outcome. After 24 weeks of salvage therapy, the median reduction in HIV-1 RNA was -1.36 log10 copies/ml (interquartile range [IQR] 0.10-2.46): at multivariable regression analysis, salvage regimens containing a TA (beta = +0.80; P = 0.02) and lamivudine (beta = +1.21; P = 0.02) as new drug had a positive effect on the reduction of HIV-1 RNA.

Development of the K65R mutation does not preclude a high rate of virological response to rescue therapy. Inclusion of a TA in the salvage regimen and the presence of a M184V mutation could have a favourable effect on virological outcome.