Clinical Trial to Assess the Efficacy of Darunavir/Ritonavir (DRV/r), Etravirine (ETV) and Raltegravir (MK-0518) in HIV Patients With Resistant Viruses

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to look at the safety and efficacy of a combination of 3 new antiretroviral drugs: darunavir, etravirine and MK-0518 (raltegravir) in patients who have multi-resistant viruses and limited treatment options. An optimized background regimen that may include nucleoside reverse transcriptase inhibitors (NRTIs) and enfuvirtide can be added, if possible, to this combination. Patients will undergo treatment for 48 weeks and virological efficacy will be evaluated at week 24.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Collaborators: Janssen-Cilag Tibotec; Merck Sharp & Dohme Corp.
• Treatments: Darunavir; Enfuvirtide; Etravirine; Raltegravir Potassium; Ritonavir

Criteria

Inclusion Criteria:

• Age: 18 years and above

• Documented HIV-1 infection.

• History of virological failure on NNRTIs (patients with a history of toxicity to nevirapine and efavirenz may be enrolled in this study).

• On a combination antiretroviral therapy for at least 8 weeks prior to the screening visit (if on tipranavir, or enfuvirtide these drugs should have been introduced more than 8 weeks before the screening visit).

• Patient naive to darunavir, etravirine and to integrase inhibitors

• Plasma viral load at screening visit over 1000 copies/ml, (no CD4 restriction).

• Genotypic resistance testing at the screening visit:

• Protease inhibitor mutations: over or equal to 3 primary protease inhibitor mutations among: D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54M, L76V, V82A/F/L/T/S, I84V, N88S and L90M (IAS list 2006) but below or equal to 3 mutations among the following: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V et L89V (virus sensitivity to darunavir/ritonavir).

• Reverse transcriptase mutations: over or equal to 3 NRTI mutations (among IAS list) and below or equal to 3 mutations among: A98G, L100I, K101Q/P/E, K103H/N/S/T, V106A/M, V108I, E138G/K/Q, V179D/E/F/G/I, Y181C/I/V/C/H/L, Y188C/H/L, G190A/C/E/Q/S, P225H, F227C/L, M230I/L, P236L, K238N/T and Y318F (virus sensitivity to etravirine)

Exclusion Criteria:

• Non effective barrier contraception in women of child bearing potential

• Pregnant women or women who are breastfeeding

• Opportunistic infection at the acute phase

• Decompensated cirrhosis (stage B or C of Child-Pugh score)

• Malignancy requiring chemotherapy or radiotherapy

• Contraindicated medications being taken by the patient (listed in protocol)

• Allergy to the active substances and expedients of darunavir, etravirine and raltegravir.

• Haemoglobin < 7g/dl, neutrophil cell count < 500/mm3, platelets < 50,000/mm3, creatinine clearance < 50 ml/mn, P. alkaline, AST, ALT or total bilirubin over or equal to 3 times normal values.

• Patients receiving experimental agents with an exclusion period for participation in other studies applicable at the screening visit of the current study.