HIV
Conditions
Keywords
HIV
Brief summary
This clinical study proposes to evaluate the combination of maraviroc with an integrase strand transfer inhibitor (either raltegravir or dolutegravir) in antiretroviral-experienced patients to document the efficacy, safety, and tolerability of this combination in order to provide clinicians with a treatment regimen that minimizes the risk of metabolic complications by avoidance of NRTI/NNRTIs and PIs. The development of an alternative ART regimen which lessens the risk of metabolic complications could improve long-term adherence and reduce the risk of certain co-morbidities associated with long-term ART use. If this new combination is found to be as efficacious as the standard regimen with enhanced tolerability and improved metabolic effects, there is great potential for altering the current practice of HIV medicine.
Detailed description
Description of the study design: The study will enroll 30 HIV-infected patients on a stable ART regimen with a suppressed HIV RNA \< 50 copies/ml for at least one year. Patients will be switched to the experimental regimen (maraviroc 300 mg twice a day plus either raltegravir 400 mg twice a day or dolutegravir 50 mg once a-day) and followed for 96 weeks. The decision to use raltegravir or dolutegravir will be left to investigator/subject preference, as the two integrate inhibitors are largely interchangeable aside from twice daily (raltegravir) vs. daily (dolutegravir) dosing. Primary endpoint: * The primary endpoint is the proportion of patients virologically suppressed (HIV RNA \< 50 copies/ml) at 48 weeks. Definitions: * Virologic suppression is an HIV RNA \< 50 copies/ml. * Virologic failure is an HIV RNA ≥ 50 copies/ml confirmed on 2 separate occasions, separated by \> 1 week after viral suppression. Secondary endpoints: * The percent change in total cholesterol, LDL, and HDL at 48 and 96 weeks. * The number of adverse events. * The proportion of patients who are virologically suppressed (HIV RNA \< 50 copies/ml) at 96 weeks. Exploratory endpoints: * Telomerase activity and telomere length measured at baseline and 24, 48, and 96 weeks.
Interventions
DRUGSwitch to Maraviroc + Raltegravir or Dolutegravir
Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection * Age between 18 and 75 years * CD4 count nadir ≥ 250 cells/mm3 * HIV RNA ≤ 50 copies/ml for ≥ 12 months while taking any ART regimen o One virologic blip ≤ 400 copies/ml permissible within the 12 months * CCR5 tropic virus as defined by: * trofile/tropism testing if available, OR * DNA trofile if no trofile/tropism test available and CD4 nadir 250-499 cells/mm3, OR * CD4 nadir ≥ 500 cells/mm3
Exclusion criteria
* Age \< 18 or \> 75 years * CD4 count nadir \< 250 cells/mm3 * Dual/mixed or X4 tropic virus if tested prior to viral suppression or if performed by DNA trofile testing at any time * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.5 times the upper limits of normal * Women who: * are currently pregnant or breastfeeding * are of child-bearing age and do not agree to remain abstinent or use (or have their partner use) an acceptable method of birth control throughout the study. Acceptable method of birth control is defined as intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy. * History of any malignancy except non-melanoma skin cancer * Concomitant use of drugs known to impact or be impacted in terms of pharmacokinetics or drug-drug interactions with either raltegravir or maraviroc. This includes: * Inducers of UGT1A1 (such as rifampin, phenytoin, phenobarbital rifabutin, St. John's wort) * CYP3A inhibitors (such as ketoconazole, itraconazole, clarithromycin, nefazodone, and telithromycin) * CYP3A inducers (such as rifampin, carbamazepine, phenobarbital and phenytoin) * Subject requires or is anticipated to require any of the prohibited medications noted in the protocol * Enrollment in an experimental protocol having received investigational agents (antiretroviral or non-antiretroviral) within 30 days of study enrollment * Chronic active hepatitis B infection as defined by presence of HBsAg * Subject has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate. * Subject is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Virologically Suppressed (HIV RNA <50 Copies/ml) at 48 Weeks. | 48 weeks | Number of patients virologically suppressed (HIV RNA \<50 copies/ml) at 48 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 96 weeks | Number of participants with adverse events |
| Number of Patients Who Are Virologically Suppressed (HIV RNA < 50 Copies/ml) | 96 weeks | Number of patients who are virologically suppressed (HIV RNA \< 50 copies/ml) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc + Raltegravir or Dolutegravir Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks
Switch to Maraviroc + Raltegravir or Dolutegravir: Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Maraviroc + Raltegravir or Dolutegravir |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 3 / 7 |
Outcome results
Primary
Number of Patients Virologically Suppressed (HIV RNA <50 Copies/ml) at 48 Weeks.
Number of patients virologically suppressed (HIV RNA \<50 copies/ml) at 48 weeks.
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc + Raltegravir or Dolutegravir | Number of Patients Virologically Suppressed (HIV RNA <50 Copies/ml) at 48 Weeks. | 5 Participants |
Secondary
Number of Participants With Adverse Events
Number of participants with adverse events
Time frame: 96 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc + Raltegravir or Dolutegravir | Number of Participants With Adverse Events | 3 Participants |
Secondary
Number of Patients Who Are Virologically Suppressed (HIV RNA < 50 Copies/ml)
Number of patients who are virologically suppressed (HIV RNA \< 50 copies/ml)
Time frame: 96 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc + Raltegravir or Dolutegravir | Number of Patients Who Are Virologically Suppressed (HIV RNA < 50 Copies/ml) | 4 Participants |