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

NCT ID: NCT01258374

Last Updated: 2019-09-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 15 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2011-12-31

Brief Summary

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.

Detailed 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.

Conditions

Integrase Inhibitors, HIV; HIV PROTEASE INHIB

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Single arm with dual therapy

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

Raltegravir

Intervention Type: DRUG

Raltegravir, 400 mg bid

Darunavir

Intervention Type: DRUG

Darunavir, 800 mg QD + ritonavir 100 mg QD

Interventions

Raltegravir

Raltegravir, 400 mg bid

Intervention Type: DRUG

Darunavir

Darunavir, 800 mg QD + ritonavir 100 mg QD

Intervention Type: DRUG

Other Intervention Names

Isentress; Prezista, Norvir.

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Clinic of Barcelona

OTHER

Sponsor Role: lead

Responsible Party

Josep Mallolas Masferrer

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Josep Mallolas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona

Locations

Hospital Clinic

Barcelona, , Spain

Countries

Spain

References

Martinez-Rebollar M, Munoz A, Perez I, Hidalgo S, Brunet M, Laguno M, Gonzalez A, Calvo M, Lonca M, Blanco JL, Martinez E, Gatell JM, Mallolas J. Pharmacokinetic study of dual therapy with raltegravir 400 mg twice daily and Darunavir/Ritonavir 800/100 mg once daily in HIV-1-infected patients. Ther Drug Monit. 2013 Aug;35(4):552-6. doi: 10.1097/FTD.0b013e31828d50ef.

Reference Type: DERIVED

PMID: 23851911 (View on PubMed)

Other Identifiers

RALDAR-HCB

Identifier Type: -

Identifier Source: org_study_id