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 - Full Text View

Sponsors and Collaborators:	French National Agency for Research on AIDS and Viral Hepatitis Tibotec Pharmaceutical Limited
Information provided by:	French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:	NCT00421551

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 III

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Darunavir Darunavir ethanolate Benzocaine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

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

Secondary Outcome Measures:

Proportion of patients with virological success between W48 and W96,
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 to virologic failure,
PI genotypic resistance mutations occurring during the follow-up,
Change in proviral DNA at D0, W48 and W96,
Change in CD4 count from D0 to W96.
Comparing plasma HIV-1 RNA genotypic resistance with DNA genotypic resistance at entry
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).
Incidence of clinical endpoints
Modification of treatment strategies and withdrawal of study treatment.
Tolerance of Darunavir (Grade 3 and 4 laboratory abnormalities and signs and symptoms).
Change in lipidic and glucidic profile and distribution of fat tissue by DEXA-scan (sub-study in 120 patients enrolled).
Self-reported adherence and symptom self-evaluation.
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.
Search for predictive factors of virological failure (level of proviral DNA, Cmin LPV, …).

Estimated Enrollment:	220
Study Start Date:	March 2007
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Darunavir Drug: ritonavir
2: Active Comparator	Drug: Darunavir Drug: ritonavir

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

Responsible Party:	ANRS ( Michele Genin )
Study ID Numbers:	2006-005962-38, ANRS 136 MONOI
Study First Received:	January 11, 2007
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00421551
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:

HIV Infections
darunavir
Ritonavir
HIV Protease Inhibitors
treatment experienced

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
Ritonavir
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Benzocaine
Retroviridae Infections
Darunavir
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
HIV Protease Inhibitors
Slow Virus Diseases
Anti-HIV Agents
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

Infection
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections

ClinicalTrials.gov processed this record on January 14, 2009