Raltegravir has no residual antiviral activity in vivo against HIV-1 with resistance-associated mutations to this drug.
OBJECTIVE
Emergence of major resistance mutations has already been associated with raltegravir regimen failure. Because of few remaining therapeutic options, the maintenance of raltegravir in the salvage regimen is often considered despite the risk of worsening resistance to integrase inhibitors. We determined whether raltegravir retains residual antiretroviral activity in vivo against viruses harbouring raltegravir mutations, and thus whether the drug can contribute to the subsequent regimen.


METHODS
This retrospective observational study reports the changes in the viral load (VL) after the withdrawal of raltegravir from patients carrying virus with resistance mutations. We selected patients under stable treatment and with stable VL during at least the previous 2 months before the withdrawal.


RESULTS
Five patients (A-E) were selected. The median changes in VL and CD4 counts at the end of the raltegravir interruption were -0.04 log copies/mL (range, -0.20 to +0.19) and +58 cells/mm(3) (range, -56 to +252), respectively.


CONCLUSIONS
All VL changes were well below the clinically relevant variation of 0.5 log copies/mL at the end of the interruption. Thus, this study indicates that, for viruses harbouring one of the two main resistance pathways described for raltegravir, no relevant antiviral activity seems to persist in vivo. Even if further observations would be useful to reinforce this conclusion, the cost/benefit and risk/benefit of maintaining raltegravir as part of a salvage regimen in the presence of raltegravir mutations seem debatable, especially in the absence of relevant antiretroviral activity in this context.
Wirden
Marc
M
Department of Virology, AP-HP, Pitié-Salpêtrière Hospital, 83 boulevard de l'Hopital, Paris, France. marc.wirden@psl.aphp.fr
Simon
Anne
A
Schneider
Luminita
L
Tubiana
Roland
R
Malet
Isabelle
I
Ait-Mohand
Hocine
H
Peytavin
Gilles
G
Katlama
Christine
C
Calvez
Vincent
V
Marcelin
Anne-Genevieve
AG
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020125:Mutation, Missense; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D019562:Viral Load
D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium