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Raltegravir Resistance Can Emerge with Low Viral Load

SUMMARY: HIV integrase inhibitor drug-resistance mutations can emerge when people taking raltegravir (Isentress) experience even low-level viral replication.

By Liz Highleyman

HIV makes random mutations as it replicates, some of which confer resistance to antiretroviral agents, thereby making drugs less effective.

As described in the March 13, 2011, issue of AIDS, Sebastien Gallien from Harvard Medical School and colleagues looked at emergence of integrase strand-transfer inhibitor resistance-associated mutations in patients with low-level viremia after switching from enfuvirtide (Fuzeon) to raltegravir.

The study authors sequenced the integrase gene of HIV obtained from participants in the French ANRS 138-Easier trial who had at least 1 test showing low-level plasma viral load (50-500 copies/mL) after starting raltegravir.


49 patients experienced at least 1 episode of low-level viral load while on raltegravir.
Integrase genotyping was successful performed on samples from 39 people (80%).
Within this group, 3 people (7.7%) had virus with significant integrase inhibitor resistance mutations.
2 people had the N155H mutation and 1 had P145S.
These mutations were not apparent in proviral HIV DNA at baseline, suggesting integrase inhibitor resistance emerged during episodes of low-level viremia.
No specific factors were identified as significant predictors of integrase inhibitor resistance, including baseline viral load, baseline or nadir (lowest-ever) CD4 cell count, genotypic susceptibility score, or degree of adherence.

Based on these findings, the investigators concluded, "Emergence of [integrase inhibitor] resistance mutations can occur during episodes of low-level viremia in patients receiving raltegravir-containing regimens."

Investigator affiliations: Section of Retroviral Therapeutics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Laboratory of Virology, Saint-Louis Hospital, Paris, France; INSERM SC 10, Villejuif, France; Department of Infectious Diseases, Saint-Louis Hospital, Paris, France; Clinical Pharmacy, Bicêtre Hospital, Le Kremlin Bicêtre, France.


S Gallien, C Delaugerre, I Charreau, et al. Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia. AIDS 25(5): 665-669 (abstract). March 13, 2011.


















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