Clinical trial NCT01245101
Conditions: HIV
Keywords: HIV raltegravir intensification replication activation
Sponsor: University of Miami
Start date: 2010-11-01; Completion date: 2013-05-01
Enrollment: 15 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This study will examine whether intensification with raltegravir of a suppressive antiretroviral regimen in HIV infected patients with poor immune restoration has a beneficial effect on cryptic viral replication and the immune system. Specifically, the investigators will examine the effect that raltegravir intensification of ART has on episomal cDNA frequencies, immune activation, CD4+ cell counts and apoptosis, and markers of microbial translocation.

Detailed description:
This is a single-center, open-label, double-arm, crossover study which will include approximately 40 HIV-infected subjects on an established suppressive HAART for at least 2 years with evidence of undetectable HIV-1 RNA levels (either \<50 copies/ml by RT-PCR or \<75 copies/ml by bDNA assay) and CD4+ count of \<350 cells/mm3 or an increase in CD4+count \<100 cells/mm3 in the last 2 years. Participants (\~20 Group 1 and \~20 in Group 2) will be randomly assigned to 1 of the 2 treatment arms described below in Table 1:

Table 1. Study groups and treatment assignments

Group A Raltegravir 400 mg PO q12h in addition to established ART (Part 1) followed by a washout period only on ART (Part 2) followed by ART (Part 3)

Group B Established ART (Part 1) followed by a washout period only on ART (Part 2) followed by raltegravir 400 mg PO q12h in addition to ART (Part 3)

The participants' pre-study HAART will be monitored so as to ensure that the distribution of NNRTI to PI-based regimens is roughly 1:1 and no higher than 2 (NNRTI):1 (PI).

The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks) (Figure 1). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.

After obtaining informed consent, patients will be enrolled into the study, a study number will be assigned, a complete history will be obtained, and a physical exam will be performed. Blood will be drawn for the following laboratory exams at Day 1 and at Weeks 1, 2, 4, 10, 16, 24, 25 26, and 40 for Group A and at Day 1 and at Weeks 1, 2, 16, 24, 25, 26, 28, 34, and 40 for Group B:

* T-cell subsets
* Plasma viral load
* Episomal viral cDNA PCR
* HLA-DR levels
* CD38 levels

Blood will also be drawn for the following laboratory exams at Day 1 and at Weeks 4, 12, 16, 24, 28, 36, and 40 for both Group A and Group B to determine

* Plasma levels of LPS, 16s ribosomal DNA, and sCD14
* T cell receptor excision circles
* CD4+ and CD8+ T-cell apoptosis

At all visits, a directed physical exam will be performed on an as-needed-basis.

Arms: arm 1: The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks. arm 2: The total duration of the study will be 40 weeks. This will include Part 1 (16 weeks) followed by Part 2 (8 weeks) followed by the crossover to Part 2 (16 weeks). During Part 1 participants in Group A will receive open-label raltegravir in addition to their established antiretroviral regimen while Group B participants will continue taking their established antiretroviral regimen for 16 weeks. After completion of Part 1, both groups will enter Part 2 that will consist of a washout period of 8 weeks during which both groups will only take their established antiretroviral regimen without raltegravir. This will be followed by Part 3 during which the two study groups will undergo a crossover with respect to the treatment assignment during Part 1 so that Group A will continue to receive their established antiretroviral regimen while Group B will receive open-label raltegravir in addition to their established antiretroviral regimen for 16 weeks.
Interventions: intervention 1: Raltegravir intervention 2: Raltegravir
Intervention descriptions: intervention 1: Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy. intervention 2: Raltegravir 400 mg twice daily in addition to subject's antiretroviral therapy.

Protocol documents: