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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00421551
• Other study ID #: 2006-005962-38
• Secondary ID: ANRS 136 MONOI
• Status: Completed
• Phase: Phase 3
• First received: January 11, 2007
• Last updated: July 17, 2013
• Start date: March 2007
• Est. completion date: February 2011

Study information

• Verified date: July 2013
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: February 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Darunavir
during the 48 first weeks of the trial, (2x300mg) twice a day between W48 and W96, (2x400mg) once a day
• ritonavir
during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day

Locations

Country	Name	City	State
France	Service des maladies infectieuses et tropicales Hopital Pitie salpetriere	Paris

Sponsors (2)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Tibotec Pharmaceutical Limited

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		W48	Yes
Secondary	Proportion of patients with virological success between W48 and W96,		W96	Yes
Secondary	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,		W96	Yes
Secondary	Time to virologic failure,		between W0 and W96	No
Secondary	PI genotypic resistance mutations occurring during the follow-up		between W0 and W96	Yes
Secondary	Change in proviral DNA at D0, W48 and W96,		W0, W48 and W96	No
Secondary	Change in CD4 count from D0 to W96.		D0, W96	No
Secondary	Comparing plasma HIV-1 RNA genotypic resistance with DNA genotypic resistance at entry		D0	No
Secondary	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).		D0 and W48	No
Secondary	Incidence of clinical endpoints		W96	Yes
Secondary	Modification of treatment strategies and withdrawal of study treatment.		between D0 and W96	Yes
Secondary	Tolerance of Darunavir (Grade 3 and 4 laboratory abnormalities and signs and symptoms).		between D0 and W96	Yes
Secondary	Change in lipidic and glucidic profile and distribution of fat tissue by DEXA-scan (sub-study in 160 patients enrolled).		W0, W48 and W96	No
Secondary	Self-reported adherence and symptom self-evaluation.		W0, W4, W24, W48, W96	No
Secondary	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.		between W0 and W96	No
Secondary	Search for predictive factors of virological failure (level of proviral DNA, Cmin LPV, …).		between W0 and W96	No
Secondary	evaluation of the mineral bone density by DEXA-scan (sub-study in 160 patients enrolled).		W96	No