Maraviroc in Immunological Non-Responder (INR) HIV-1-infected Subjects
Suboptimal improvement in cluster of differentiation 4 (CD4) cell count is not uncommon in HIV-1-infected patients with suppressed plasma HIV-Ribonucleic acid (RNA) levels, and a decrease in CD4 cell count in patients with suppressed or low level viremia has been observed.
Although the efficacy of current antiretroviral medications is well established, some antiviral combinations are very effective in suppressing HIV-1 load whereas do not exert any effect on immune reconstitution.
Both T-cell immune activation and fibrosis of peripheral lymphoid tissue could create an environment in which CD4 T cell count decrease in the setting of low or suppressed plasma viremia is likely to occur.
Another fascinating hypothesis, which has still to be elucidated, is that reconstitution of the depleted CD4 pool is blocked by an excess of glycoprotein 120 (gp120) HIV-1 protein. This extra-production could be counteracted by an inhibitor of the chemokine (C-C motif) receptor 5 (CCR5) co-receptor that represents one of the major docking tools of HIV-1.
With this in mind, the investigators would like to propose and design a pilot exploratory clinical trial involving a population of HIV-1-infected patients that rapidly reached a virologic suppression without a reconstitution of their immune system.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Use of Maraviroc (MVC) in Immunological Non-responder HIV-1-infected Patients.|
- CD4 counts > 200/uL or recovery of CD4 > 25% in 2 consecutive time-points. [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Subjects in this group will add Maraviroc to their current HAART.
Maraviroc is administered BID according to the other drugs within HAART; dosage ranges from 150 mg to 600 mg bid.
Other Name: Maraviroc brand name in the EC is Celsentri.
No Intervention: 2
Subjects in this group will continue their current HAART without adding Maraviroc.
- Evaluate the clinical efficacy of HAART intensification with MVC as treatment of HIV-1 infection in patients with a CD4 count ≤ 200 cells/uL and/or a recovery of CD4 cells < 25% compared to the HAART initiation and with a complete and stable virologic suppression after 12 months of HAART. Patients could also being included if their CD4 slope has been stable without any improvement, with an absolute value around 200 cells/uL.
- Evaluate the effects of HAART intensification with MVC on the modification of immunologic and virologic parameters.
- Evaluate the tolerability of HAART intensification with MVC and the appearance of drug-related side effects.
This will be a randomised, multicenter, study that will evaluate HAART intensification with MVC as treatment of HIV-1 infection in patients with a CD4 count ≤ 200 cells/uL and/or a recovery of CD4 cells < 25% compared to the HAART initiation and/or a stable CD4 slope without any improvement, with an absolute value around 200 cells/uL and with a complete and stable virologic suppression after 12 months of HAART.
|Servizio Regionale di Immunologia Clinica e Tipizzazione Tissutale, Azienda Ospedaliero-Universitaria|
|Torrette di Ancona, AN, Italy, 60126|
|Clinica di Malattie Infettive, Policlinico, Universita' degli Studi|
|Bari, BA, Italy, 70124|
|Clinica di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Spedali civili|
|Brescia, BS, Italy, 25125|
|Divisione di Malattie Infettive, Ospedale S. Maria Annunziata|
|Antella, FI, Italy, 50011|
|Clinica di Malattie Infettive, Ospedale San Martino|
|Genova, GE, Italy, 16132|
|Divisione di Malattie Infettive, Ospedale San Gerardo|
|Monza, MB, Italy, 20052|
|Polo di Medicina Chirurgia e Odontoiatria, Polo Didattico S. Paolo|
|Milano, MI, Italy, 20124|
|I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario Luigi Sacco|
|Milano, MI, Italy, 20157|
|U.O di Malattie Infettive, Fondazione San Raffaele del Monte Tabor|
|Milano, MI, Italy, 20132|
|Divisione Clinicizzata di Malatie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"|
|Milano, MI, Italy, 20157|
|Clinica delle Malattie Infettive, Policlinico Universitario|
|Modena, MO, Italy, 41100|
|U.O. Malattie Infettive, Ospedale S. Spirito|
|Pescara, PE, Italy, 65100|
|Clinica delle Malattie Infettive, Policlinico Monteluce|
|Perugia, PG, Italy, 06126|
|IV Divisione di Malattie Infettive, INMI Lazzaro Spallanzani|
|Roma, RM, Italy, 00149|
|III Divisione di Malattie Infettive, I.N.M.I Lazzaro Spallanzani|
|Roma, RM, Italy, 00149|
|Clinica delle Malattie Infettive, Policlinico "Tor Vergata"|
|Roma, RM, Italy, 00133|
|Istituto Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore|
|Roma, RM, Italy, 00168|
|U.O. Malattie Infettive, Azienda Policlinico Umberto I|
|Roma, RM, Italy, 00161|
|Clinica delle Malattie Infettive ,Ospedale Amedeo di Savoia|
|Torino, TO, Italy, 10149|
|Divisione Dipartimento Urgenze Infettivologiche ad Alta Complessità e correlate all'AIDS, Ospedale Cotugno|
|Napoli, Italy, 80131|
|Principal Investigator:||Stefano Rusconi, M.D.||Universita' degli Studi di Milano, Italy|