Clinical trial NCT00520897: Integrase Inhibitor (MK-0518) Viral Decay
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: chronic HIV infection
Human Immunodeficiency Virus
Treatment Experienced
Lead sponsor: Canadian Immunodeficiency Research Collaborative
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2007-08-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Participant must be HIV-1 infected
2. Participant must be 18 years old
3. 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).
4. 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
5. Female participant must agree to use two methods of birth control or abstinence during the period of the study
6. Participant has to have signed full informed consent

Exclusion Criteria:

1. Participant who would have difficulty participating in a trial due to non-adherence or substance abuse
2. Participant who has taken mono or dual antiretroviral therapy in the past
3. Participant who has had a VL \> 50 copies/ml on any antiretroviral regimen
4. 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
5. Participant with a malignancy
6. Participant with other significant underlying disease (non-HIV) that might impinge upon disease progression or death
7. Participant with an active AIDS-defining illness in the past six months
8. Participant who is pregnant

Primary outcomes:
measure: change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48
timeFrame: 48 weeks
Secondary outcomes:
measure: evaluated the effect of raltegravir intensification on blood CD4+ T cell populations
timeFrame: 48 & 96 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic
state: Ontario
Study officials:
affiliation: Women's College Hospital
name: Mona Loutfy, MD
role: PRINCIPAL_INVESTIGATOR
References: