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Antivir Ther. 2011;16(6):937-40. doi: 10.3851/IMP1826.

Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal.

Author information

1
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, Paris, France. charlotte.charpentier@bch.aphp.fr

Abstract

BACKGROUND:

Little is known in HIV-2 infection about the kinetics of disappearance of raltegravir (RAL)-resistant virus after RAL withdrawal.

METHODS:

RAL was interrupted in four highly antiretroviral-experienced HIV-2-infected patients exhibiting a virological failure when receiving RAL. Integrase gene was sequenced from plasma samples collected at the time of RAL failure and at further time points following RAL withdrawal.

RESULTS:

At the time of RAL withdrawal, virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H, T97A/N155H and T97A/Y143C. In patient 1, the G140S/Q148R double-mutant was still detected at month (M)7 and at M11 after stopping RAL, but was no longer detected at M15. Regarding patient 2, the double-mutant E92Q/N155H was still present at M2 and M8 after stopping RAL, and was no longer detected at M12. In patient 3, RAL-resistant virus with T97A/N155H mutations were still present 1 month after stopping RAL, and were no longer detected at M14. Regarding patient 4, the mutant T97A/Y143C was still detected at M1 and M3 following RAL withdrawal. At M18 after RAL stop, integrase genotypic pattern evolved to T97A/Y143G.

CONCLUSIONS:

Persistence of HIV-2 RAL-resistant mutants was observed in all the key genetic RAL resistance pathways. These findings have clinical implications especially in HIV-2-infected patients for whom therapeutic arsenal is limited compared to HIV-1, since the persistence of resistant mutants might compromise the possible efficacy of upcoming second-generation integrase inhibitors.

PMID:
21900727
DOI:
10.3851/IMP1826
[Indexed for MEDLINE]

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