Resistance Can Emerge with Low Viral Load
HIV integrase inhibitor drug-resistance mutations
can emerge when people taking raltegravir (Isentress)
experience even low-level viral replication.
makes random mutations as it replicates, some of which confer
resistance to antiretroviral agents, thereby making drugs
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
(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.
patients experienced at least 1 episode of low-level viral
load while on raltegravir.
genotyping was successful performed on samples from 39
this group, 3 people (7.7%) had virus with significant
integrase inhibitor resistance mutations.
people had the N155H mutation and 1 had P145S.
mutations were not apparent in proviral HIV DNA at baseline,
suggesting integrase inhibitor resistance emerged during
episodes of low-level viremia.
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.
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
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.
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
March 13, 2011.