Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

NCT ID: NCT01293123

Last Updated: 2019-10-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-12-31

Brief Summary

The primary aim of this study is to determine the effects of the HIV integrase inhibitor, raltegravir, in cerebrospinal fluid (CSF). This will be accomplished by collecting CSF before and after initiation of either raltegravir or another antiretroviral, efavirenz, each in combination with two other antiretrovirals. Assessments will include HIV RNA levels (viral load), neuropsychological testing, mood assessments, and quality of life assessments.

Detailed Description

Cognitive disorders continue to be a common complication of HIV disease even though potent antiretroviral drugs can reduce HIV below detectable levels and restore immune function. Concentrations of most antiretrovirals in the nervous system are only a fraction of concentrations in blood. As a result, HIV can continue to be present in the nervous system when it is below detection in blood. A recently approved drug, raltegravir, reaches therapeutic concentrations in cerebrospinal fluid and may be effective at controlling HIV replication in the primary target cells in the brain, macrophages and microglia. Based on this, raltegravir may be a particularly effective drug for treating HIV disease in the nervous system. The purpose of this study is to determine the effects of raltegravir in the nervous system by measuring HIV in the CSF (via lumbar puncture, also known as spinal taps) before and after initiation of raltegravir-containing antiretroviral therapy. CSF is an accessible fluid that provides a window into brain processes, including HIV replication and inflammation. The potency of raltegravir will be estimated by calculating the change in HIV viral load in CSF over time. These changes will be compared to those following initiation an efavirenz-containing regimen in a separate group of individuals. Two additional drugs (tenofovir disoproxil fumarate, emtricitabine) will be combined with either raltegravir or efavirenz. Neuropsychological performance, mood, sleep and quality of life assessment will also be compared. Participants will be randomly assigned to either raltegravir- or efavirenz-containing therapy.

Conditions

HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Raltegravir

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: DRUG

raltegravir 400 mg PO twice daily

Efavirenz

Group Type: ACTIVE_COMPARATOR

Efavirenz

Intervention Type: DRUG

efavirenz 600 mg PO once daily

Interventions

Raltegravir

raltegravir 400 mg PO twice daily

Intervention Type: DRUG

Efavirenz

efavirenz 600 mg PO once daily

Intervention Type: DRUG

Other Intervention Names

tenofovir disoproxil fumarate 300 mg PO once daily; emtricitabine 200 mg PO once daily; tenofovir disoproxil fumarate 300 mg PO once daily; emtricitabine 200 mg PO once daily

Eligibility Criteria

Inclusion Criteria

1. Men and women aged 18-65 years;

2. Integrase inhibitor-naive subjects with clinical indication to initiate RAL under the supervision of their HIV care provider;

3. Baseline detectable HIV-1 RNA levels ≥ 5000 copies/mL in plasma and ≥ 500 copies/mL in CSF;

4. Absolute T-cell CD4+ subset between 200-500/mm3

5. Individual willing to undergo serial lumbar punctures as outlined in study evaluations;

6. Subject able to give informed consent to all study procedures (if cognitively impaired, the individual must pass an evaluation to ensure adequate comprehension of the consent document and procedures);

7. Susceptibility to all study drugs on Monogram Biosciences PhenoSense GT assay.

Exclusion Criteria

1. Contraindication to lumbar puncture, such as current coagulopathy, thrombocytopenia (platelets below 50,000/µL), or use of anticoagulants;

2. Cognitive, psychiatric, or substance use disorders or any other medical conditions that would interfere with study participation, in the opinion of the investigator;

3. Major opportunistic infections (e.g., pneumonia, tuberculosis) within 30 days;

4. Use of prescribed drugs with known substantial interactions with the study drugs;

5. Positive HCV serology;

6. HIV-associated dementia/Global Deterioration Scale ≥4;

7. Pregnancy;

8. Serum creatinine higher than 2.0 mg/dL;

9. Total bilirubin or alanine or aspartate transaminases more than 3 times the upper limit of normal

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

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Scott Letendre

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott Letendre, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

UCSD Antiviral Research Center

San Diego, California, United States

Countries

United States

Other Identifiers

11-0067

Identifier Type: -

Identifier Source: org_study_id