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

Sponsor

French National Agency for Research on AIDS and Viral Hepatitis (Other)

Overall Status

Completed

CT.gov ID

NCT00421551

Collaborator

Tibotec Pharmaceutical Limited (Industry)

225

Enrollment

Location

Arms

47.1

Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Darunavir Drug: ritonavir	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

225 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Prezista Drug: ritonavir during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day Other Names: 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 Names: Prezista Drug: ritonavir during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day Other Names: Norvir

Arm

Intervention/Treatment

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 Names:

Prezista

Drug: ritonavir

during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day

Other Names:

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 Names:

Prezista

Drug: ritonavir

during the first 48 weeks, 100mg twice a day between W48 and W96, 100mg once a day

Other Names:

Norvir

Outcome Measures

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 [W48]

Secondary Outcome Measures

Proportion of patients with virological success between W48 and W96, [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, [W96]
Time to virologic failure, [between W0 and W96]
PI genotypic resistance mutations occurring during the follow-up [between W0 and W96]
Change in proviral DNA at D0, W48 and W96, [W0, W48 and W96]
Change in CD4 count from D0 to W96. [D0, W96]
Comparing plasma HIV-1 RNA genotypic resistance with DNA genotypic resistance at entry [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). [D0 and W48]
Incidence of clinical endpoints [W96]
Modification of treatment strategies and withdrawal of study treatment. [between D0 and W96]
Tolerance of Darunavir (Grade 3 and 4 laboratory abnormalities and signs and symptoms). [between D0 and W96]
Change in lipidic and glucidic profile and distribution of fat tissue by DEXA-scan (sub-study in 160 patients enrolled). [W0, W48 and W96]
Self-reported adherence and symptom self-evaluation. [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. [between W0 and W96]
Search for predictive factors of virological failure (level of proviral DNA, Cmin LPV, …). [between W0 and W96]
evaluation of the mineral bone density by DEXA-scan (sub-study in 160 patients enrolled). [W96]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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