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CompletedNCT00460382ANRS139 TRIOUpdated Sep 17, 2010

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

A Phase 2 interventional study of raltegravir potassium and darunavir/ritonavir in HIV Infections, sponsored by French National Agency for Research on AIDS and Viral Hepatitis. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2010-09-17.

Sponsored by French National Agency for Research on AIDS and Viral Hepatitis · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
103
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • HIV Infections

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Keywords

  • HIV infections
  • HIV integrase inhibitor
  • etravirine
  • darunavir
  • MK 0518
  • raltegravir
  • Treatment Experienced
  • Antiviral drug resistance
03

In context

HIV Infections

4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 103 is above the median of 83 across 3,251 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

French National Agency for Research on AIDS and Viral Hepatitis is the lead sponsor of 83 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age: 18 years and above
  • Documented HIV-1 infection.
  • History of virological failure on NNRTIs (patients with a history of toxicity to nevirapine and efavirenz may be enrolled in this study).
  • On a combination antiretroviral therapy for at least 8 weeks prior to the screening visit (if on tipranavir, or enfuvirtide these drugs should have been introduced more than 8 weeks before the screening visit).
  • Patient naive to darunavir, etravirine and to integrase inhibitors
  • Plasma viral load at screening visit over 1000 copies/ml, (no CD4 restriction).

  • Genotypic resistance testing at the screening visit:

    • Protease inhibitor mutations: over or equal to 3 primary protease inhibitor mutations among: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54M, L76V, V82A/F/L/T/S, I84V, N88S and L90M (IAS list 2006) but below or equal to 3 mutations among the following: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V et L89V (virus sensitivity to darunavir/ritonavir).
    • Reverse transcriptase mutations: over or equal to 3 NRTI mutations (among IAS list) and below or equal to 3 mutations among: A98G, L100I, K101Q/P/E, K103H/N/S/T, V106A/M, V108I, E138G/K/Q, V179D/E/F/G/I, Y181C/I/V/C/H/L, Y188C/H/L, G190A/C/E/Q/S, P225H, F227C/L, M230I/L, P236L, K238N/T and Y318F (virus sensitivity to etravirine)

Exclusion criteria

Exclusion Criteria:

  • Non effective barrier contraception in women of child bearing potential
  • Pregnant women or women who are breastfeeding
  • Opportunistic infection at the acute phase
  • Decompensated cirrhosis (stage B or C of Child-Pugh score)
  • Malignancy requiring chemotherapy or radiotherapy
  • Contraindicated medications being taken by the patient (listed in protocol)
  • Allergy to the active substances and expedients of darunavir, etravirine and raltegravir.
  • Haemoglobin \< 7g/dl, neutrophil cell count \< 500/mm3, platelets \< 50,000/mm3, creatinine clearance \< 50 ml/mn, P. alkaline, AST, ALT or total bilirubin over or equal to 3 times normal values.
  • Patients receiving experimental agents with an exclusion period for participation in other studies applicable at the screening visit of the current study.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
103 participants (actual)

Interventions

  • Drugraltegravir potassium

    400 mg twice a day

    Also known as: Isentress

  • Drugdarunavir/ritonavir

    2 pills of 300 mg twice a day

    Also known as: Prezista

  • Drugetravirine

    2 pills of 100 mg twice a day

    Also known as: TMC125

  • DrugOptimized background regimen

    NRTIs and or enfuvirtide (investigator choice)

    Also known as: OBT, enfuvirtide

06

What researchers measure

Primary outcomes

  1. 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

  1. 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

  2. HIV RNA level evolution between baseline and week 48

    Time frame: from week 0 to 48

  3. HIV proviral DNA and 2LTR circle HIV DNA between baseline and week 48

    Time frame: from week 0 to 48

  4. Number and type of resistance mutations in case of virologic failure occurrence

    Time frame: from week 0 to 48

  5. CD4 lymphocyte count and proportion evolution between baseline and week 48

    Time frame: from week 0 to 48

  6. HIV infection progression

    Time frame: from week 0 to 48

  7. Frequency of the study regimen modifications and interruption

    Time frame: from week 0 to 48

  8. Study regimen tolerance

    Time frame: from week 0 to 48

  9. Study regimen adherence

    Time frame: from week 0 to 48

  10. Association between study drugs' minimum concentrations at week 4 and week 12 and virologic success at week 24

    Time frame: from week 4 to 24

  11. Evolution of pharmacokinetics parameters of study drugs in the PK substudy

    Time frame: betwwen week 1 and 4

07

Study locations

1 site
  • Hôpital Gustave Dron, Service Maladies Infectieuses
    Tourcoing, 59208, France
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 17, 2010, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00460382
Lead sponsor
French National Agency for Research on AIDS and Viral Hepatitis
Collaborators
Merck Sharp & Dohme LLC, Janssen-Cilag Tibotec
First posted
Apr 13, 2007
Start date
May 2007
Primary completion
Mar 2008
Completion
Sep 2009
Last update
Sep 17, 2010

Study contacts

Yazdan YAZDANPANAH, MD PHD
principal investigator · Hôpital Tourcoing FRANCE
Geneviève CHENE, MD PHD
study director · INSERM U897 BORDEAUX FRANCE

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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