HIV Infections
Conditions
Keywords
Treatment Experience, On enfuvirtide
Brief summary
The primary objective of this study is: To assess the virologic effect of changing enfuvirtide to MK-0518(raltegravir) in human immunodeficiency virus type 1(HIV-1) infected patients who have an undetectable level of serum human immunodeficiency virus(HIV) (\< 75 copies/ml by branch deoxyribonucleic acid (bDNA) assay, \< 50 copies/ml by Ultrasensitive Polymerase Chain Reaction(PCR) assay) on their current HIV medication regimen. Hypothesis: HIV-1 infected individuals well controlled on an enfuvirtide containing regimen with HIV RNA levels below limits of quantification can safely have the investigational integrase inhibitor, MK-0518 substituted for enfuvirtide without loss of virologic suppression.
Detailed description
Human immunodeficiency virus type 1(HIV-1) infected patients who have had an undetectable viral load on an enfuvirtide containing regimen at the Kaiser Permanente Hayward, Los Angeles, San Francisco, and Santa Clara Medical Centers will be enrolled. Patients will receive open label MK-0518 (raltegravir) 400mg orally twice a day as substitution for enfuvirtide for 24 weeks.
Interventions
DRUGraltegravir
This is a single-arm, open-label, non-randomized pilot study in human immunodeficiency virus type 1 (HIV-1) positive patients who have an undetectable viral load on their current enfuvirtide containing medication regimen. The treatment regimen will consist of replacing enfuvirtide with MK-0518 400 mg twice a day given as part of the patient's HIV medication regimen. The study regimen will be administered for 24 weeks, with patients given the option of continuing on the study medication past that time if they wish to. Patients serve as their own control as they have viral control (HIV ribonucleic acid (RNA) below limits of quantification) for at least 6 months with enfuvirtide prior to switch to raltegravir.
Sponsors
Merck Sharp & Dohme LLC
Kaiser Permanente
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must meet all of the following inclusion criteria to be eligible for participation in this study. 1. Subject is ≥ 18 years of age and able to understand and willing to sign a written informed consent form, which must be obtained prior to initiation of the study. 2. Documented laboratory diagnosis of HIV-1 infection (positive Enzyme-linked immunosorbent assay (ELISA) HIV-1 antibody test confirmed by western blot, p24 assay, HIV-1 RNA, or culture). 3. Have documented plasma HIV-1 RNA level(s) of \< 75 copies/ml by branched deoxyribonucleic acid(bDNA) assay, or \< 50 copies/ml by Ultrasensitive Polymerase Chain Reaction(PCR) for at least 6 months prior to screening visit. 4. Currently receiving a stable antiretroviral regimen consisting of enfuvirtide plus at least 2 other antiretrovirals for at least 6 months. 5. Negative serum pregnancy test (females of childbearing potential only) and are willing to use an adequate method of contraception throughout the duration of the study.
Exclusion criteria
* Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Undetectable Human Immunodeficiency Virus (HIV) Viral Load at Week 24. | 24 Weeks | To assess the virologic effect of changing enfuvirtide to MK-0518 (raltegravir) in human immunodeficiency virus type 1 (HIV-1) infected patients who have an undetectable level of serum HIV (undetectable level of serum HIV defined as \< 75 copies/ml by bDNA assay or \< 50 copies/ml by Ultrasensitive PCR assay) on their current HIV medication regimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change in Cluster of Differentiation 4(CD4) Cell Count From Baseline at Week 24 | 24 Weeks | To study the immunologic effect of changing enfuvirtide to MK-0518 (raltegravir) in HIV-1 infected patients who have an undetectable level of serum HIV (undetectable serum HIV defined as \< 75 copies/ml by bDNA assay or \< 50 copies/ml by Ultrasensitive PCR assay)on their current HIV medication regimen. |
Countries
United States
Participant flow
Recruitment details
A multicenter study that enrolled patients from 11 Kaiser Permanente Human Immunodeficiency Virus (HIV) clinics in California. 54 patients were screened. Two patients did not meet protocol inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| MK-0518 (Raltegravir) Open label, single arm. All patients to receive MK-0518 400mg orally twice a day for 24 weeks, as substitution for enfuvirtide. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Relocated | 1 |
Baseline characteristics
| Characteristic | MK-0518 (Raltegravir) |
|---|---|
| Age, Continuous | 53 years |
| Number of Past Antiretrovials Used | 15 medications |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 48 Participants |
| Time of Prior Antiretroviral Therapy Use | 15 years |
| Time on Enfuvirtide Therapy | 997 days |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 52 |
| serious Total, serious adverse events | 3 / 52 |
Outcome results
Primary
Number of Patients With Undetectable Human Immunodeficiency Virus (HIV) Viral Load at Week 24.
To assess the virologic effect of changing enfuvirtide to MK-0518 (raltegravir) in human immunodeficiency virus type 1 (HIV-1) infected patients who have an undetectable level of serum HIV (undetectable level of serum HIV defined as \< 75 copies/ml by bDNA assay or \< 50 copies/ml by Ultrasensitive PCR assay) on their current HIV medication regimen.
Time frame: 24 Weeks
Population: Analysis used the intent to treat (ITT) population, defined as all patients who received at least one dose of raltegravir.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0518 (Raltegravir) | Number of Patients With Undetectable Human Immunodeficiency Virus (HIV) Viral Load at Week 24. | 49 participants |
Secondary
Average Change in Cluster of Differentiation 4(CD4) Cell Count From Baseline at Week 24
To study the immunologic effect of changing enfuvirtide to MK-0518 (raltegravir) in HIV-1 infected patients who have an undetectable level of serum HIV (undetectable serum HIV defined as \< 75 copies/ml by bDNA assay or \< 50 copies/ml by Ultrasensitive PCR assay)on their current HIV medication regimen.
Time frame: 24 Weeks
Population: Analysis was per intention to treat (ITT) population defined as all patients who received at least one dose of raltegravir.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-0518 (Raltegravir) | Average Change in Cluster of Differentiation 4(CD4) Cell Count From Baseline at Week 24 | 32 cells/mm^3 |