(Isentress) Found to Be an Effective Substitute for Enfuvirtide (Fuzeon)
Ronald Baker, PhD
(Isentress) is an HIV integrase inhibitor that is administered orally, while
enfuvirtide (Fuzeon) is an HIV fusion
(entry) inhibitor administered by subcutaneous injection. Enfuvirtide is FDA-approved
for treatment-experienced HIV patients who exhibit continued HIV replication despite
ongoing antiretroviral therapy.
Raltegravir is also FDA-approved for treatment-experienced patients.
to results of a new study published in the May
28, 2009 online issue of the Journal of Acquired Immune Deficiency Syndromes,
raltegravir (Isentress) can be safely and effectively substituted for enfuvirtide
in treatment-experienced patients on a stable, virologically suppressive enfuvirtide-containing
study published in 2008 in the journal AIDS found similar results.
primary objective of the present study was to determine the safety and efficacy
of changing from enfuvirtide to raltegravir in HIV patients with an undetectable
viral load for at least 6 months.
Study investigators enrolled 52 eligible
patients at 11 Kaiser Permanente facilities in California. Participants were at
least 18 years old and were on suppressive antiretroviral medications at baseline.
At the start of the study, 400 mg twice-daily oral raltegravir was substituted
for twice-daily enfuvirtide injections; the other background drugs in their regimens
did not change.
The primary endpoint was the percentage of participants
who achieved undetectable HIV RNA (below the limit of quantification) in an intent-to-treat
analysis after 24 weeks on a raltegravir-based regimen.
After 24 weeks of therapy with raltegravir, 49 patients (94.2%) had undetectable
HIV viral load.
The median CD4 cell increase was 32 cells/mm3.
Questionnaires showed that patients who switched to raltegravir experienced improved
satisfaction with their regimen.
Adverse events while on raltegravir were infrequent and mild.
on these results, the study authors concluded, "In treatment-experienced
patients on a stable virologically suppressive enfuvirtide-containing regimen,
raltegravir can safely be substituted for enfuvirtide."
patients would be expected to prefer taking a twice-daily oral tablet compared
with using twice-daily injections. However, the finding that raltegravir was safe
and effective in addition to being an oral drug could not be assumed without conducting
this or a similar study.
potential for improvement in quality of life for patients using raltegravir versus
enfuvirtide cannot be overstated. Almost all patients taking enfuvirtide experience
injection site reactions. These reactions may be mild to moderate, but occasionally
they are severe. Reactions on the skin where enfuvirtide is injected may include
itching, swelling, redness, pain or tenderness, hardened skin, and bumps (nodules).
In clinical trials, serious adverse events leading to study discontinuation occurred
in 12.9% of patients (114 of 885) in the enfuvirtide arm, compared with 10.7%
(12 of 112) in the control arm.
far, there have been no serious adverse effects reported in patients using raltegravir,
which was approved by the FDA in October 2007 -- the first HIV integrase inhibitor
to be approved by the agency.
Department of Internal Medicine, Kaiser
Permanente, Los Angeles, CA; Division of Infectious Diseases, Kaiser Permanente,
Hayward, CA; Division of Infectious Diseases, Kaiser Permanente, San Francisco,
CA; Division of Infectious Diseases, Kaiser Permanente, West Los Angeles, CA;
Division of Research, Kaiser Permanente, Oakland, CA.
on Raltegravir Posted on HIV and Hepatitis.com
Full US Prescribing Information
Patient Information about Raltegravir
on Fuzeon Posted on HIV and Hepatitis.com
Full U.S. Prescribing Information
Patient Information about Fuzeon
Towner, D Klein, HL Kerrigan, and others. Virologic
Outcomes of Changing Enfuvirtide to Raltegravir in HIV-1 Patients Well Controlled
on an Enfuvirtide Based Regimen: 24-Week Results of the CHEER Study Journal
of Acquired Immune Deficiency Syndromes. May 28, 2009 [Epub ahead of print].
HB Fung and Y Guo. Enfuvirtide: A
Fusion Inhibitor for the Treatment of HIV Infection. Clinical Therapy
26(3): 352-378. March 2004.