Switch to Maraviroc + Integrase Inhibitor

Phase 3

Completed

Conditions: HIV

Interventions: Drug: Switch to Maraviroc + Raltegravir or Dolutegravir

Registration Number: NCT01896921

Lead Sponsor: University of Maryland, Baltimore

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Maraviroc + Raltegravir or Dolutegravir	Switch to 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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
Number of Participants With Adverse Events	96 weeks	Number of participants with adverse events