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Switch from Enfuvirtide to Raltegravir in Highly Treatment-experienced HIV-1-infected Patients: A Randomized Open-label Non-inferiority Trial, Easier--ANRS 138
Nathalie De Castro*1, J Braun2, I Charreau2, G Pialoux3, L Cotte4, C Katlama5, C Delaugerre1, I Madelaine-Chambrin1, J-P Aboulker2, J-M Molina1, and the ANRS 138 Study Group
1St Louis Hosp, Paris, France; 2INSERM SC10, Villejuif, France; 3Hosp Tenon, Paris, France; 4Hotel Dieu Hosp., Lyon, France; and 5Hosp Pitie-Salpetriere, Paris, France
Background: Among
patients with multi-resistant HIV infection, enfuvirtide (E-based) regimens
(EBR) can durably suppress viral replication. However, due
to the inconveniency of twice-daily subcutaneous injections and the high incidence of injection site reactions,
alternatives to EBR are desirable.
Methods: We
randomized 170 patients with triple-class resistant HIV-1 infection and plasma HIV
RNA <400 copies/mL for at least 3 months under EBR, 1:1 to either the maintenance
of EBR or the switch to a raltegravir (R-based) regimen. The primary endpoint
was the cumulative proportion of patients with virologic failure, defined as a confirmed
plasma HIV RNA ≥400 copies/mL until week 24.
Results: Patients’
characteristics at baseline were well balanced across the 2 arms: median age 47.9
years, 85% male, 52% CDC stage C, 13.6 years median HAART duration, 2.3 years median
EBR duration, 393 cells/mm3 median baseline CD4 cell count, 44 cells/mm3
median nadir CD4 cell count. One patient withdrew his consent before being
dosed and was excluded from the analysis. Through week 24, virologic failure
was observed in 1 of 85 (1.2%) patients in EBR arm and 1 of 84 patients (1.2%)
in R-based arm in an intent-to-treat analysis (D 0.01%; 95%CI –4.4, +4.5).
In the per protocol analysis, none of the 82 (0%) patients in the EBR arm and 1
of the 82 patients (1.2%) in the R-based arm (D 1.22%; 95%CI –2.4, +4.8) experienced
virologic failure. At week 24, 89% of patients in both arms had plasma HIV-1
RNA levels <50 copies/mL. No significant CD4 changes occurred in either arm through
week 24. Neither an AIDS-defining event nor death occurred during the study. Incidence
of grade 3 to 4 adverse events was 11% and 19% in the EBR
and R-based arms, respectively
(p = 0.12). Incidence of grade 3 to 4 laboratory abnormalities was 6%
and 12% in the EBR and R-based
arms, respectively (p = 0.17).
Conclusions: In highly treatment-experienced patients with suppressed viral
replication under EBR, a switch from enfuvirtide to raltegravir has non-inferior
antiviral activity as compared to the maintenance of the EBR, with a similar
safety profile.
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