Effect of Integrase Inhibitor (MK-0518) on Decay of Low Level Viral Replication in HIV Reservoirs in Infected Individuals Who Initiated Conventional Antiretroviral Therapy During the Chronic Phase of Infection
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48
Study Overview
Brief Summary
The eradication of HIV by antiretroviral therapy has thus far been elusive. It has been consistently demonstrated that a pool of latently infected, resting CD4+ T cells persists in the majority of HIV-infected individuals receiving antiretroviral therapy in whom plasma viremia has been successfully suppressed for prolonged periods of time; this pool has emerged as the major obstacle in achieving the eradication of HIV. We believe that MK-0518 can further the decay and suppression of HIV-1 in patients who have been virologically suppressed for a prolonged period of time on effective cART (≥ 4 years).
Detailed Description
The trial is a prospective, double-blind, randomized, placebo-controlled study with two phases: phase I to 48 weeks and phase II to 96 weeks with the primary analysis at 48 weeks. HIV-infected individuals who are taking their first standard cART regimen for at least four years with complete viral suppression. Upon enrollment, he/she will be randomized to one of two arms: the MK-0518 arm or the control arm. As each participant reaches week 48, he/she will be unblinded and those in the MK-0518 arm will continue taking MK-0518. Based on the results of an interim analysis, the control arm will be rolled over to receive MK-0518 for 48 weeks. After the screening, baseline visits and week 4 safety visit, follow-up visits will occur every 8 weeks for both arms.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant must be HIV-1 infected
- •Participant must be 18 years old
- •Participant must be taking first standard cART with 2-3 NRTIs and 1-2 PIs or an NNRTI for at least four years (first cART regimen may include changes due to toxicity but not due to virologic failure).
- •Participant must have a VL < 50 copies/ml (using the standard available methods of detection) during the entire time on standard cART except for initial fall of VL and a maximum of two non-consecutive blips of < 100 copies/ml that the study investigator deems to be not clinically significant
- •Female participant must agree to use two methods of birth control or abstinence during the period of the study
- •Participant has to have signed full informed consent
Exclusion Criteria
- •Participant who would have difficulty participating in a trial due to non-adherence or substance abuse
- •Participant who has taken mono or dual antiretroviral therapy in the past
- •Participant who has had a VL > 50 copies/ml on any antiretroviral regimen
- •Participant with any of the following abnormal laboratory test results in screening:
- •Hemoglobin < 100 g/L
- •Neutrophil count < 750 cells/L
- •Platelet count < 50,000 cells/L
- •AST or ALT > 5X the upper limit of normal
- •Creatinine > 250 mol/L
- •Participant with a malignancy
- •Participant with other significant underlying disease (non-HIV) that might impinge upon disease progression or death
- •Participant with an active AIDS-defining illness in the past six months
- •Participant who is pregnant
Arms & Interventions
MK0518 + cART
Raltegravir + standard of care combined antiretroviral therapy
Intervention: Raltegravir (MK0518) (Drug)
MK0518 + cART
Raltegravir + standard of care combined antiretroviral therapy
Intervention: Leukopheresis (Procedure)
MK0518 + cART
Raltegravir + standard of care combined antiretroviral therapy
Intervention: Sigmoid Biopsy (Procedure)
Placebo + cART
Placebo + standard of care combined antiretroviral therapy
Intervention: Placebo (Drug)
Placebo + cART
Placebo + standard of care combined antiretroviral therapy
Intervention: Leukopheresis (Procedure)
Placebo + cART
Placebo + standard of care combined antiretroviral therapy
Intervention: Sigmoid Biopsy (Procedure)
Outcomes
Primary Outcomes
change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48
Time Frame: 48 weeks
evaluate the change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48 in participants randomized to the raltegravir arm (400mg raltegravir) for 48 weeks in addition to their current standard combination antiretroviral regimen versus the control arm, who remained on their current standard combination antiretroviral regimen.
Secondary Outcomes
- evaluated the effect of raltegravir intensification on blood CD4+ T cell populations(48 & 96 weeks)