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 - Full Text View

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

Drug Information available for: Ritonavir Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

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

Lambert-Niclot S, Flandre P, Valantin MA, Soulie C, Fourati S, Wirden M, Sayon S, Pakianather S, Bocket L, Masquelier B, Dos Santos G, Katlama C, Calvez V, Marcelin AG. Similar evolution of cellular HIV-1 DNA level in darunavir/ritonavir monotherapy versus triple therapy in MONOI-ANRS136 trial over 96 weeks. PLoS One. 2012;7(7):e41390. doi: 10.1371/journal.pone.0041390. Epub 2012 Jul 25.

Katlama C, Valantin MA, Algarte-Genin M, Duvivier C, Lambert-Niclot S, Girard PM, Molina JM, Hoen B, Pakianather S, Peytavin G, Marcelin AG, Flandre P. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010 Sep 24;24(15):2365-74. doi: 10.1097/QAD.0b013e32833dec20.


Responsible Party:	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
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:	July 17, 2013
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):


HIV Infections darunavir Ritonavir HIV Protease Inhibitors treatment experienced

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on March 01, 2015