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

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

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.

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

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