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Study Comparing Efficacy and Safety of Darunavir Boosted With Ritonavir to HART With 2 NRTI and Darunavir Boosted With Ritonavir in HIV-1 Infected Patients ANRS136

This study has been completed.
Sponsor:
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00421551
First received: January 11, 2007
Last updated: April 8, 2011
Last verified: April 2011
History of Changes
  Purpose

The purpose of this study is to evaluate whether a monotherapy of boosted darunavir is able to maintain the virological success until 48 weeks in comparison to a standard therapy 2 INTI + darunavir/r in HIV infected patients with full viral suppression.


Condition Intervention Phase
HIV Infections
 Drug: Darunavir
Drug: ritonavir
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Multicenter Study With Non-inferiority Hypothesis, Comparing the Availability to Maintain a Complete Viral Suppression by a Monotherapy of Darunavir/r to a NRTI Containing Regimen Including Darunavir/r, in HIV-1 Infected Patients With Previous Prolonged Complete Viral Suppression. ANRS 136 MONOI

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • Proportion of patients with virological success, the virological failure is defined as 2 consecutive plasma viral load measurements greater or equal to 400 cp/ml within 2 weeks at W48 [ Time Frame: W48 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of patients with virological success between W48 and W96, [ Time Frame: W96 ] [ Designated as safety issue: Yes ]
  • Proportion of patients with HIV-1 RNA below 50 copies/mL, between 50 to 400 copies/mL and > 400 copies/ml from D0 to W96, [ Time Frame: W96 ] [ Designated as safety issue: Yes ]
  • Time to virologic failure, [ Time Frame: between W0 and W96 ] [ Designated as safety issue: No ]
  • PI genotypic resistance mutations occurring during the follow-up [ Time Frame: between W0 and W96 ] [ Designated as safety issue: Yes ]
  • Change in proviral DNA at D0, W48 and W96, [ Time Frame: W0, W48 and W96 ] [ Designated as safety issue: No ]
  • Change in CD4 count from D0 to W96. [ Time Frame: D0, W96 ] [ Designated as safety issue: No ]
  • Comparing plasma HIV-1 RNA genotypic resistance with DNA genotypic resistance at entry [ Time Frame: D0 ] [ Designated as safety issue: No ]
  • Quantification of HIV RNA in the genital compartment between D0 and W48 (sub-study with 40 patients enrolled, 20 patients in each arm of strategy). [ Time Frame: D0 and W48 ] [ Designated as safety issue: No ]
  • Incidence of clinical endpoints [ Time Frame: W96 ] [ Designated as safety issue: Yes ]
  • Modification of treatment strategies and withdrawal of study treatment. [ Time Frame: between D0 and W96 ] [ Designated as safety issue: Yes ]
  • Tolerance of Darunavir (Grade 3 and 4 laboratory abnormalities and signs and symptoms). [ Time Frame: between D0 and W96 ] [ Designated as safety issue: Yes ]
  • Change in lipidic and glucidic profile and distribution of fat tissue by DEXA-scan (sub-study in 160 patients enrolled). [ Time Frame: W0, W48 and W96 ] [ Designated as safety issue: No ]
  • Self-reported adherence and symptom self-evaluation. [ Time Frame: W0, W4, W24, W48, W96 ] [ Designated as safety issue: No ]
  • The proportion of patients with HIV RNA below 50 copies/mL in darunavir/r monotherapy arm after resuming 2 previous NRTIs in case of virological failure. [ Time Frame: between W0 and W96 ] [ Designated as safety issue: No ]
  • Search for predictive factors of virological failure (level of proviral DNA, Cmin LPV, …). [ Time Frame: between W0 and W96 ] [ Designated as safety issue: No ]
  • evaluation of the mineral bone density by DEXA-scan (sub-study in 160 patients enrolled). [ Time Frame: W96 ] [ Designated as safety issue: No ]

Enrollment: 225
Study Start Date: March 2007
Study Completion Date: February 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Darunavir
during the 48 first weeks of the trial, (2x300mg) twice a day between W48 and W96, (2x400mg) once a day
Other Name: Prezista
Drug: ritonavir
during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day
Other Name: Norvir
Active Comparator: 2 Drug: Darunavir
during the 48 first weeks of the trial, (2x300mg) twice a day between W48 and W96, (2x400mg) once a day
Other Name: Prezista
Drug: ritonavir
during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day
Other Name: Norvir

Detailed Description:

The chronicity of the disease which will require treatment over decades, long-term adverse events associated with standard combined antiretroviral therapy, emphasize the need for simpler, alternative treatment strategies for HIV infection. The goal of antiretroviral therapy in 2006 is the durability of treatment with less toxicity and reduced exposure to drugs. Previous studies have shown that single boosted PI maintenance therapy such as lopinavir (LPV/r), were effective in maintaining virological efficacy. Furthermore, in case of virological failure, limited resistance has been described. darunavir/r, a new PI, has been shown to be highly potent, exhibits a high genetic barrier to resistance and appears to be well tolerated. This study aimed to evaluate whether darunavir/r can represent a potential strategy therapeutic as single therapy in patients who have full virologic suppression At entry, subjects with HIV RNA below 50 cp/ml switch from their current therapy which can be 2 NRTI and IP, 2 NRTI and NNRTI, 3 NRTI to darunavir/r with their 2 NRTIs for 8 weeks (Phase I). If patients remain below 50 cp/ml and has no intolerance to darunavir at week -4, they are included in the phase II and will be randomized either to receive darunavir/r alone or to continue 2 NRTI and darunavir/r for until W48 (Phase II). Patients will be monitored at W4, W8 and then every 8 weeks until W48 for the primary endpoint. To evaluate the durability and safety of this strategy, patients will be followed up to W96

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed HIV-1 infection.
  • Documented level of HIV-1 RNA at initiation of antiretroviral treatments
  • Prior antiretroviral regimen, including at least 2 NRTIs combined to 1 PI or NNRTI or a third NRTI for at least 18 months prior to study entry.
  • CD4 count of 200 cells per mm3 or greater.
  • Viral load below 400 copies per ml within 18 months prior to entry and below 50 copies per mL at entry.
  • Willing to use acceptable methods of contraception

Exclusion Criteria:

  • Previous virological failure under prior PI-based regimen.
  • Prior therapy in the darunavir.
  • HIV-2 infected patients.
  • Absence of documented level of HIV-1 RNA at initiation of antiretroviral treatments
  • Hepatitis B or C infection within 90 days prior to study entry.
  • Therapies including interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressors at study entry.
  • Serious acute illness requiring systemic treatment or hospitalization in the 14 days prior to study entry.
  • Treatment for an active AIDS defining opportunistic infection within 30 days prior to screening
  • Drug or alcohol use or any dependence that would interfere with compliance.
  • Pregnancy or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00421551

Locations
France
Service des maladies infectieuses et tropicales Hopital Pitie salpetriere
Paris, France, 75013
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Tibotec Pharmaceutical Limited
Investigators
Principal Investigator: Christine Katlama, MD AP-HP hopital Pitié salpetriere Paris
Study Chair: Philippe Flandre Inserm UMR S720
  More Information

No publications provided by French National Agency for Research on AIDS and Viral Hepatitis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Michele Genin, ANRS
ClinicalTrials.gov Identifier: NCT00421551     History of Changes
Other Study ID Numbers: 2006-005962-38, ANRS 136 MONOI
Study First Received: January 11, 2007
Last Updated: April 8, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
HIV Infections
darunavir
Ritonavir
HIV Protease Inhibitors
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
HIV Protease Inhibitors
 Ritonavir
Darunavir
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013