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

Background: The effect of the HIV reverse transcriptase K65R mutation on virological response to salvage therapy has not been clearly defined. Methods: 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. Results: Among 145 subjects included over a 197 person-year follow-up, the estimated probability of virological response (VIR, 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 VIR 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 log(10) 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. Conclusions: 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.