Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression

Study Overview
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Brief Summary
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An intensification with the HIV-1 integrase inhibitor Raltegravir (RAL) of a stable HAART regimen with persistent HIV-1 viral suppression could increase the slope of decay of the HIV-1 latent reservoir.

Detailed Description
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While highly active antiretroviral therapy (HAART) reduces plasma HIV-1 levels to below the limits of detection with standard assays, replication-competent virus persist in a stable, latent reservoir in resting CD4+ T cells. So, there is a rapid resumption in plasma viremia when therapy is interrupted. In addition to cellular reservoir, other pharmacologically privileged areas such as the central nervous system and the genital tract might act as additional sources of residual virus in patients with undetectable levels of plasma HIV-1 RNA. There is great current interest in strategies for depleting and eliminating this reservoir. The antiviral potency of current regimens emerges as an important determinant of complete viral control. In certain patients, the latent reservoir decay can be hastened with treatment intensification. An intensification with the HIV-1 integrase inhibitor Raltegravir (RAL) of a stable HAART regimen with persistent HIV-1 viral suppression could increase the slope of decay of the HIV-1 latent reservoir. This could provide further insight into this area, decrease the size of latent reservoir, and translate into clinical benefits for patients being simplified to maintenance monotherapy with RAL or in the HIV-1 rebound kinetics and slope after a programmed treatment interruption.

Official Title
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Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: MK-0518 400mg twice a day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected adults (+18 years old). Complete virological suppression (<50 copies/mL) for += 12 months, including at least 3 times during the last year. Patients on HAART regimen including a PI or an NNRTI and at least two nucleotide inhibitors. Voluntary written informed consent. Exclusion Criteria: Pregnancy, or fertile women willing to be pregnant. Active substance abuse or major psychiatric disease. Presence of drug-related mutations or any polymorphism or mutation associated to MK-0518 resistance prior to first HAART (only if genotype is available).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>MK-0518 400mg twice a day | Drug: MK-0518 400mg twice a day<br>* Raltegravir, MK-0518<br>* Other names: Raltegravir;|
| No Intervention: B<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs |  | Basal, week 12, week 24 and week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL) |  | Basal, week 1, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| Blips during the study (> 50 copies/mL, preceded and followed by determinations < 50 copies/mL in previous and posterior controls) |  | Basal, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| Lymphocyte activation marker CD8+HLADR+CD38+ |  | Basal, week 2, week 4, week 12, week 24 and week 48. | 
| Raltegravir plasma trough concentration. |  | Week 12, week 24 and week 48 | 
| Level of apoptosis in CD4 and CD8 T cells. |  | Week 48 and week 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Raltegravir, MK-0518, Treatment intensification, HIV-1 latency, HIV eradication, treatment experienced