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

Tracking Information
First Submitted Date ICMJE	January 11, 2007
First Posted Date ICMJE	January 12, 2007
Last Update Posted Date	July 18, 2013
Study Start Date ICMJE	March 2007
Actual Primary Completion Date	June 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 10, 2009)	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 ]
Original Primary Outcome Measures ICMJE; (submitted: January 11, 2007)	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
Change History	Complete list of historical versions of study NCT00421551 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 10, 2009)	Proportion of patients with virological success between W48 and W96, [ Time Frame: 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 Frame: W96 ]; Time to virologic failure, [ Time Frame: between W0 and W96 ]; PI genotypic resistance mutations occurring during the follow-up [ Time Frame: between W0 and W96 ]; Change in proviral DNA at D0, W48 and W96, [ Time Frame: W0, W48 and W96 ]; Change in CD4 count from D0 to W96. [ Time Frame: D0, W96 ]; Comparing plasma HIV-1 RNA genotypic resistance with DNA genotypic resistance at entry [ Time Frame: D0 ]; 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 ]; Incidence of clinical endpoints [ Time Frame: W96 ]; Modification of treatment strategies and withdrawal of study treatment. [ Time Frame: between D0 and W96 ]; Tolerance of Darunavir (Grade 3 and 4 laboratory abnormalities and signs and symptoms). [ Time Frame: between D0 and W96 ]; 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 ]; Self-reported adherence and symptom self-evaluation. [ Time Frame: W0, W4, W24, W48, W96 ]; 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 ]; Search for predictive factors of virological failure (level of proviral DNA, Cmin LPV, …). [ Time Frame: between W0 and W96 ]; evaluation of the mineral bone density by DEXA-scan (sub-study in 160 patients enrolled). [ Time Frame: W96 ]
Original Secondary Outcome Measures ICMJE; (submitted: January 11, 2007)	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, …).
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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
Official Title ICMJE	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
Brief Summary	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.
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
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	HIV Infections
Intervention ICMJE	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
Study Arms	Experimental: 1 Interventions: Drug: Darunavir Drug: ritonavir; Active Comparator: 2 Interventions: Drug: Darunavir Drug: ritonavir
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 10, 2009)	225
Original Enrollment ICMJE; (submitted: January 11, 2007)	220
Actual Study Completion Date	February 2011
Actual Primary Completion Date	June 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	France
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00421551
Other Study ID Numbers ICMJE	2006-005962-38; ANRS 136 MONOI
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
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 )
Study Sponsor ICMJE	French National Agency for Research on AIDS and Viral Hepatitis
Collaborators ICMJE	Tibotec Pharmaceutical Limited
Investigators ICMJE	Principal Investigator: Christine Katlama, MD AP-HP hopital Pitié salpetriere Paris Study Chair: Philippe Flandre Inserm UMR S720
PRS Account	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Verification Date	July 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP