Safety Study of Lopinavir/Ritonavir With Raltegravir in HIV-infected Patients

Safety and Efficacy of Lopinavir/Ritonavir in Combination With Raltegravir in HIV-infected Patients

A single center, open label, 48-week study of lopinavir/ritonavir in combination with raltegravir. 30 patients, both naïve and experienced, will be enrolled. 15 treatment naïve patients and 15 treatment experienced patients enrolled

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: lopinavir/ritonavir and raltegravir

Detailed Description

This is an open-labeled, non-randomized exploratory trial in selected volunteers who meet the stated enrollment criteria. This study will assess the impact of lopinavir/ritonavir in combination with raltegravir on HIV-1

Patients will be evaluated frequently over the 52 weeks of the protocol. Patients will be seen at screening, baseline, week 4, 12, 24, 36, 48, and 52, to include physical examination, assessment for the development of AIDS-defining conditions, hematology, chemistry, lipid profile, CD4, CD8 cell counts, plasma HIV-1 RNA ultrasensitive, and assessment of adverse events. If HIV-1 RNA becomes detectable, this will be repeated for confirmation with 2 weeks. HIV genotyping and phenotyping will be performed on patients who demonstrate repetitive plasma viral load levels of > 1,000 copies/mL.

An interim analysis will be performed when all patients have reached the week 24 visit.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HIV-1 infection, as documented by any licensed ELISA test kit, and confirmed by Western blot, positive HIV-1 blood culture, positive HIV serum antigen, or plasma viremia at any time prior to study entry. If no record exists, testing must occur at screening.
2. Males and non-pregnant females > 18 years of age. (Children are being excluded as they are immunologically different than adults)
3. HIV-1 RNA > 1000 copies/ml for both patient naive and experienced to antiretroviral therapy in order for phenotypic susceptibility to be performed. There in no inclusion criteria for CD4 count.
4. Treatment experienced patients , defined as having taken medications from two of the following three classes of antiretrovirals: NRTI, NNRTI, or PI must have phenotypic susceptability to lopinavir/ritonavir as resulted by Phenosense GT
5. Laboratory tests ( Cbc w/diff, comprehensive metabolic panel) within pre-specified limits
6. Able to sign the informed consent, and is willing to comply with the requirements of this clinical trial.
7. Available for at least 52 weeks of follow up
8. If female and of child bearing potential must consent to remain abstinent throughout the study period and for 30 days after the last dose of study medications.( this is standard language)

Exclusion Criteria:

1. Pregnant or breast-feeding woman (pregnant women are being excluded as drug kinetics are different in pregnancy and the dynamics of immune reconstitution are unknown in this group)
2. Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or isolated cutaneous Kaposi's Sarcoma that is not being treated; those with prior cancer diagnosis, such as lymphomas must have been disease-free for at least 5 years
3. Absolute neutrophil count < 500, platelet count < 50,000, hemoglobin < 8 gm/dL
4. Evidence of end-organ disease, defined as follows: renal (calculated creatinine clearance of less than 50 mL/min); liver (liver-associated enzymes > 3 times the upper limits of normal)
5. Grade 3 (ACTG Grading Scale) or higher cholesterol or triglyceride elevations
6. Acute, serious infection requiring prescription drug therapy within 30 days prior to study entry
7. In the opinion of the investigator, there is evidence of an active ongoing opportunistic infection
8. Must not currently be undergoing treatment for an opportunistic infection.
9. Use of immune stimulation agents known to impact CD4 cell count in the peripheral circulation, to include IL2, interferon, G-CSF, GM-CSF, etc.
10. Use of immune suppressant drugs, with the exception of < 10 mg/day of prednisone .
11. Unwillingness to remain abstinent for duration of study
12. Experimental vaccines, to include HIV vaccines.
13. Patient who is currently enrolled in an experimental protocol, or is receiving an experimental medication.
14. Patients on 2 NRTIs with an NNRTI and a PI combination will not be allowed in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; open label single arm	Drug: lopinavir/ritonavir and raltegravir; lopinavir/ritonavir 400/100 mg po b.id. in combination with raltegravir 400 mg po b.i.d.; Other Names: Kaletra, Isentress

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of this trial is to evaluate the percentage of patients with HIV-1 RNA below 50 copies at week 48 receiving lopinavir/ritonavir in combination with raltegravir	week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effect of lopinavir/ritonavir in combination with raltegravir in maintaining virological suppression	weeks 12, 24, 36, and 48
To evaluate the change from baseline in plasma HIV-1 RNA at weeks 12, 24, 36, and 48	weeks 12, 24, 36, and 48

Collaborators and Investigators

• Sponsor: Saint Michael's Medical Center
• Collaborators: Abbott
• Investigators: Principal Investigator: Jihad Slim, MD, Saint Michael's Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: September 12, 2008
• First Submitted That Met QC Criteria: September 12, 2008
• First Posted (Estimate): September 15, 2008

Study Record Updates

• Last Update Posted (Estimate): July 20, 2011
• Last Update Submitted That Met QC Criteria: July 19, 2011
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: HIV; Treatment Experienced; Protease Inhibitor; Naive; Integrase Inhibitor
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Ritonavir; Lopinavir
• Other Study ID Numbers: INV 08/08