Dual Therapy With Raltegravir and Darunavir/Ritonavir in HIV Infected Patients. (RALDAR)

Hospital Clinic of Barcelona

Status: Completed

Conditions: Integrase Inhibitors, HIV; HIV PROTEASE INHIB

Treatments: Drug: Darunavir; Drug: Raltegravir

Study type: Observational

Funder types: Other

Identifiers

NCT01258374

RALDAR-HCB

Details and patient eligibility

About

While 3-drug regimens remain standard of care, concerns exist regarding the safety of multi-drug regimens taken for a lifetime. Problems with nucleoside analogue therapy prompted successful trials with ritonavir (RTV) boosted PI monotherapy, however long term safety and efficacy of such regimens remains unknown. Clinical trials have shown Raltegravir (RAL) to have potent activity when patients have few active background drugs; it has a superior lipid profile compared with EFV and LPV/RTV. Darunavir/r (DRV) is a potent, well tolerated PI with few GI side effects and lipid disturbances and with a high genetic barrier. The investigators hypothesized that RAL/DRV would be a well tolerated and effective regimen for those patients who are failing nucleoside reverse transcriptase inhibitors based regimens, due to poor tolerability or resistance. The investigators also would like to explore the plasma pharmacokinetics of Raltegravir combined with Darunavir in a sub-group of 12 HIV-infected patients.

Full description

Hypothesis

• NRTI-sparing regimens are attractive options to avoid NRTI-associated toxicity and to provide a full active regimen in patients with some extent of NRTI resistance.
• Raltegravir (RAL) and Darunavir (DRV) are potent "third drugs" and they provide a synergistic inhibition of 2 different steps in HIV replication.
• DRV has a high genetic barrier, and could be an excellent accompanying drug for Raltegravir, providing a potent, safe and well tolerated dual therapy to patients who are failing NNRTI based treatments.

Objectives:

• To describe the safety, tolerability and efficacy of the combination of Raltegravir and Darunavir after 24 weeks of follow up in HIV infected patients failing a NRTI based regimen.
• To describe plasma pharmacokinetics of Raltegravir when combined with Darunavir 800mg QD in HIV-infected patients.

Enrollment: 15 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented HIV infection
• Naïve to Raltegravir.
• CD4 cell count above 200 cell/mm3.
• No history of failure to PI containing regimens.
• No evidence of PI mutations (IAS-mutation list) by genotype test.
• Failing to a NRTI based regimen.
• The treating physician decides a NRTI sparing regimen which includes DRV/r 800/100 mg QD plus Raltegravir 400 mg BID.
• Signed informed consent form
• In opinion of the investigator, the patient should be considered clinically stable and could follow regular visits as scheduled per protocol.

Exclusion criteria

• Patients receiving drugs considered contraindicated to Raltegravir and DRV/r. Contraindicated drugs are: rifampin, fenitoin, phenobarbital in the case of raltegravir. Pravastatin, astemizole, sildenafil, are contraindicated in combination with DRV/r.
• Pregnancy
• Documented PI mutations

Trial design

15 participants in 1 patient group

Single arm with dual therapy

Description:

Dual therapy RAL 400 mg bid + DRV/r 800/100 mg QD

Treatment:

Drug: Raltegravir

Drug: Darunavir