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HIV-1-infected treatment-naive and -experienced patients: resistance to integrase inhibitors


Integrase strand transfer inhibitor ( INSTI ) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice, were described.

Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017.
Failure was defined as two consecutive plasma viral loads ( VL ) more than 50 copies/mL.

Among the 674 patients, 359 were failing on Raltegravir, 154 on Elvitegravir and 161 on Dolutegravir therapy.
Overall, 90% were experienced patients and 389 ( 58% ) patients showed no INSTI RAMs ( resistance-associated mutations ) at failure.

The strongest factors associated with emergence of at least one INSTI mutation were high viral load at failure ( odds ratio, OR = 1.2 per 1 log10 copies/mL increase ) and low genotypic sensitivity score ( GSS ) ( OR = 0.08 for GSS greater than or equal to 3 versus GSS = 0-0.5 ).

Patients failing Dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing Raltegravir ( OR = 0.57, P = 0.02 ) or Elvitegravir ( OR = 0.45, P = 0.005 ).

Among the 68 patients failing a first-line regimen, 11/41 ( 27% ) patients on Raltegravir, 7/18 ( 39% ) on Elvitegravir and 0/9 on Dolutegravir had viruses with emergent INSTI RAMs at failure.

In conclusion, these results have confirmed the robustness of Dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care. ( Xagena )

Marcelin AG et al, J Antimicrob Chemother 2019; Epub ahead of print

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