Efficacy and Tolerance of the Switch From Enfuvirtine to Raltegravir in Antiretroviral Therapy Regimen in HIV Patients With Undetectable Viral Load (EASIER)

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase

Completed

Phase 3

Conditions

HIV Infections

Treatments

Drug: FTC/TDF + EFV or LPV/R +T20

Drug: FTC/TDF + EFV or LPV/R

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00454337

ANRS 138 EASIER

2007-000162-20

Details and patient eligibility

About

Switching from enfuvirtide to raltegravir in the treatment of HIV-infected patients who sustain viral suppression with a combination therapy including enfuvirtide (or : with an enfuvirtide-based combination therapy)

Full description

In patients who have failed under the three main classes of antiretroviral agents (NRTI, NNRTI and PI) and in whom the control of viral replication in the plasma has ultimately been achieved with enfuvirtide, the aim is to sustain this virological success for as long as possible to thus enable satisfactory immune reconstitution, avoid further accumulation of viral mutations conferring resistance to the drugs and protect the patient from the risk of opportunistic disease and death.

Indeed, enfuvirtide is the lead compound in the new class of antiretroviral drugs which inhibit the fusion of HIV-1 virus with its target cell. Its in vivo efficacy was demonstrated during the pivotal studies TORO 1 and 2. Despite its efficacy, maintaining long-term treatment with enfuvirtide is nonetheless difficult for patients because of the constraints related to twice-daily subcutaneous parenteral injections. Furthermore, these subcutaneous injections are associated with inflammatory reactions at the injection site in 98 per cent of patients, without any reduction in frequency or severity over time. It is thus critical for patients who are well controlled by enfuvirtide to be able to simplify their treatment by replacing enfuvirtide with another active compound taken by mouth, which would enable maintenance of the virological response and acceptable safety in patients who have usually failed under the three main classes of antiretroviral drugs. A new antiviral compound, viral integrase inhibitor called raltegravir, could be proposed instead of enfuvirtide.

Enrollment

170 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Chronic HIV-1 infection
Treatment with a well-tolerated combination of antiretroviral drugs unchanged for at least 3 months, including enfuvirtide
Absence of any uncontrolled opportunistic disease
No restrictions on CD4 lymphocyte levels
Plasma HIV-1 RNA below 400 copies per ml for at least 3 months (at least two consecutive tests below 400 copies per ml prior to inclusion in the study, not including that on W -4)
For women of childbearing age, use of mechanical contraception during any sexual intercourse and negative pregnancy test (plasma ß HCG) at W -4

Exclusion criteria

HIV-2 infection
Plasma HIV-1 RNA levels above 400 copies/ml on one occasion during the 3 months prior to screening (or the pre-inclusion visit at W -4)
Poor compliance with antiretroviral therapy current at W -4
Current treatment with an investigational drug (except cohort ATU)
Patient previously treated with an integrase inhibitor in the context of a clinical study
Woman who is pregnant or likely to become so, is breastfeeding or refuses to use contraception
Multiple drug therapy ongoing or necessary in the foreseeable future for Kaposi's disease or lymphoma
Treatment with interferon ongoing or necessary in the foreseeable future for chronic hepatitis B or C
Acute hepatitis whatever the case, or decompensated cirrhosis
Current treatment with interferon, interleukin or anti-HIV vaccine
Any condition (including, but not limited to, the consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol
Significant biological abnormalities (hemoglobin below 8g per dl, polynuclear neutrophils below 750 per mm3, platelets below 50,000 per mm3, serum creatinine above 3 times the level deemed normal by the laboratory (N), ASAT or ALAT above 5N, serum lipase above 2N) and total bilirubin above 2N (except if the patient is receiving atazanavir or indinavir)
Concomitant treatments including one or more compounds interacting with UGT1A1
- anti-infective agents: rifampicin/rifampin
- psychotropic/anti-epileptic drugs: phenytoin, phenobarbital.