NCT00460382·Phase 2·INTERVENTIONAL

Clinical Trial to Assess the Efficacy of Darunavir/Ritonavir (DRV/r), Etravirine (ETV) and Raltegravir (MK-0518) in HIV Patients With Resistant Viruses

Enfuvirtide Other Completed

Status

Completed

Phase

Phase 2

Enrollment

103

Locations

Results

Not posted

Publications

Study summary

What the protocol is testing.

The purpose of this study is to look at the safety and efficacy of a combination of 3 new antiretroviral drugs: darunavir, etravirine and MK-0518 (raltegravir) in patients who have multi-resistant viruses and limited treatment options. An optimized background regimen that may include nucleoside reverse transcriptase inhibitors (NRTIs) and enfuvirtide can be added, if possible, to this combination. Patients will undergo treatment for 48 weeks and virological efficacy will be evaluated at week 24.

Full detailed description

Methods: A phase II pilot, prospective, open label, single arm multicentric clinical trial assessing a darunavir/ritonavir, etravirine and MK-0518-containing regimen, if possible associated to an optimized background regimen that may include NRTIs and enfuvirtide, in HIV-1 infected patients failing combination antiretroviral therapy with multi-resistant viruses. Treatment strategy: Patients will receive raltegravir (MK-0518), darunavir/ritonavir (TMC114/r) and etravirine (TMC125) and if possible an optimized background therapy. * raltegravir (MK-0518) (400 mg x 2/d = one 400 mg pill twice daily) * darunavir (600 mg x 2/d= two 300 mg pills twice daily with meal) * ritonavir (100 mg x 2/d = one 100 mg pill twice daily with meal) * etravirine (200 mg x 2/d = two 100 mg pills twice daily with meal) * if possible an optimized background therapy: may include NRTI(s) and enfuvirtide but not nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). NRTIs choice is left to the clinician's discretion. Enfuvirtide is highly recommended in enfuvirtide-naive patients but is left to the clinician. Main outcome: proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at W24. Secondary outcomes: proportions of patients with HIV RNA levels of less than 50 copies/ml at week 48, with HIV RNA levels of less than 400 copies/ml at week 24 and 48; HIV RNA level evolution between baseline and week 48; HIV proviral DNA and 2LTR circle HIV DNA between baseline and week 48; number and type of resistance mutations in case of virologic failure occurrence; CD4 lymphocyte count and proportion evolution between baseline and week 48; HIV infection progression; frequency of the study regimen modifications and interruption; study regimen tolerance; study regimen adherence; association between study drugs' minimum concentrations at week 4 and virologic success at week 24; evolution of pharmacokinetic parameters of study drugs between week 1 and week 4 in the Pharmacokinetic substudy. Sample size: 103 patients Enrollment period: 24 weeks Patient's participation duration: 52 weeks An extended follow-up (from week 52 to week 96) has been added in April 2008.

Interventions

Treatment arms and agents.

DRUG

raltegravir potassium

400 mg twice a day

DRUG

darunavir/ritonavir

2 pills of 300 mg twice a day

DRUG

etravirine

2 pills of 100 mg twice a day

DRUG

Optimized background regimen

NRTIs and or enfuvirtide (investigator choice)

Timeline

From registration to results.

First posted
Apr 13, 2007
Study start
May 2007
Primary completion
Mar 2008
Study completion
Sep 2009
Results posted
Not reported
Registry updated
Sep 17, 2010

Outcomes

What the study measures.

Primary outcomes

Proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at week 24

Time frame · week 24

Secondary outcomes

Proportions of patients with HIV RNA levels of less than 50 copies/ml at week 48, with HIV RNA levels of less than 400 copies/ml at weeks 24 and 48

Time frame · week 24 and 48

HIV RNA level evolution between baseline and week 48