Raltegravir Cerebrospinal Fluid Pharmacodynamic Study in HIV-Infected Individuals

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01293123

Enrollment

Registered

2011-02-10

Start date

2011-12-31

Completion date

2013-12-31

Last updated

2019-10-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV

Keywords

HIV, raltegravir, cerebrospinal fluid

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.

Interventions

DRUGRaltegravir

raltegravir 400 mg PO twice daily

DRUGEfavirenz

efavirenz 600 mg PO once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Cerebrospinal Fluid HIV RNA Levels	180 days	Slope of decline of HIV RNA levels in CSF over time

Secondary

Measure	Time frame	Description
Neuropsychological Performance	180 days	Change in neuropsychological performance over 180 days
Measure of Mood	180 days	Change in mood over 180 days
Measure of Sleep	180 days	Change in self-reported sleep performance over 180 days.
Measure of Quality of Life	180 days	Change in self-report quality of life over 180 days

Countries

United States

Participant flow

Participants by arm

Arm	Count
Raltegravir Raltegravir: raltegravir 400 mg PO twice daily	1
Efavirenz Efavirenz: efavirenz 600 mg PO once daily	1
Total	2

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	0	1

Baseline characteristics

Characteristic	Efavirenz	Raltegravir	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	1 Participants	1 Participants	2 Participants
Age, Continuous	36 years STANDARD_DEVIATION 0	26 years STANDARD_DEVIATION 0	31 years STANDARD_DEVIATION 0
Region of Enrollment United States	1 participants	1 participants	2 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	1 Participants	1 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 1	0 / 1
other Total, other adverse events	0 / 1	0 / 1
serious Total, serious adverse events	0 / 1	0 / 1

Population: Insufficient enrollment for data analysis

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026