Clinical trial NCT00884858: Maraviroc in Immunological Non-Responder (INR) HIV-1-infected Subjects
Official title: Use of Maraviroc (MVC) in Immunological Non-responder HIV-1-infected Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV-1
CD4
INR
HIV-1 infection
extreme immunological compromission
treatment experienced
Lead sponsor: ASST Fatebenefratelli Sacco
Sponsor class: OTHER
First posted: 2009-04-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Objectives:

* 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.

Design:

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.

Eligibility criteria: Inclusion Criteria:

* age \> or = 18
* HIV-Abs positivity detected by ELISA and confirmed by Western-Blot
* CD4 lymphocytes \< 200/uL and/or CD4 recovery \< 25% after at least 12 months of stable HAART
* HIV-RNA \< 50 cp/mL during the last 12 months
* negative pregnancy test at least 14 days prior to treatment
* understanding and signing the informed consent

Exclusion Criteria:

* allergy/intolerance to the study drug
* less than 1 year from any treatment with immunomodulatory agents
* current OIs or neoplasms
* current CVD or EKG abnormalities
* current respiratory tract diseases or COPD
* treatment with steroids within 4 weeks from treatment beginning
* suspect of autoimmune disorder or chronic inflammatory disease
* active IVDUs or alcohol addicts
* AST and ALT \> 2.5 ULD
* serum creatinine \> 1.5 ULD
* ANC \< 1000/uL
* hemoglobin \< 10 g/dL
* platelets \< 75.000/uL
* reticulocytes \> 2%
* Karnofsky score \< 50

Primary outcomes:
measure: CD4 counts > 200/uL or recovery of CD4 > 25% in 2 consecutive time-points.
timeFrame: 3 and 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Torrette di Ancona
country: Italy
facility: Servizio Regionale di Immunologia Clinica e Tipizzazione Tissutale, Azienda Ospedaliero-Universitaria
state: AN
city: Bari
country: Italy
facility: Clinica di Malattie Infettive, Policlinico, Universita' degli Studi
state: BA
city: Brescia
country: Italy
facility: Clinica di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Spedali civili
state: BS
city: Antella
country: Italy
facility: Divisione di Malattie Infettive, Ospedale S. Maria Annunziata
state: FI
city: Genova
country: Italy
facility: Clinica di Malattie Infettive, Ospedale San Martino
state: GE
city: Monza
country: Italy
facility: Divisione di Malattie Infettive, Ospedale San Gerardo
state: MB
city: Milano
country: Italy
facility: Polo di Medicina Chirurgia e Odontoiatria, Polo Didattico S. Paolo
state: MI
city: Milano
country: Italy
facility: U.O di Malattie Infettive, Fondazione San Raffaele del Monte Tabor
state: MI
city: Milano
country: Italy
facility: Divisione Clinicizzata di Malatie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
state: MI
city: Milano
country: Italy
facility: I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario Luigi Sacco
state: MI
city: Modena
country: Italy
facility: Clinica delle Malattie Infettive, Policlinico Universitario
state: MO
city: Pescara
country: Italy
facility: U.O. Malattie Infettive, Ospedale S. Spirito
state: PE
city: Perugia
country: Italy
facility: Clinica delle Malattie Infettive, Policlinico Monteluce
state: PG
city: Roma
country: Italy
facility: Clinica delle Malattie Infettive, Policlinico "Tor Vergata"
state: RM
city: Roma
country: Italy
facility: III Divisione di Malattie Infettive, I.N.M.I Lazzaro Spallanzani
state: RM
city: Roma
country: Italy
facility: IV Divisione di Malattie Infettive, INMI Lazzaro Spallanzani
state: RM
city: Roma
country: Italy
facility: U.O. Malattie Infettive, Azienda Policlinico Umberto I
state: RM
city: Roma
country: Italy
facility: Istituto Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore
state: RM
city: Torino
country: Italy
facility: Clinica delle Malattie Infettive ,Ospedale Amedeo di Savoia
state: TO
city: Napoli
country: Italy
facility: Divisione Dipartimento Urgenze Infettivologiche ad Alta Complessità e correlate all'AIDS, Ospedale Cotugno
Study officials:
affiliation: Universita' degli Studi di Milano, Italy
name: Stefano Rusconi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rusconi S, Vitiello P, Adorni F, Colella E, Foca E, Capetti A, Meraviglia P, Abeli C, Bonora S, D'Annunzio M, Di Biagio A, Di Pietro M, Butini L, Orofino G, Colafigli M, d'Ettorre G, Francisci D, Parruti G, Soria A, Buonomini AR, Tommasi C, Mosti S, Bai F, Di Nardo Stuppino S, Morosi M, Montano M, Tau P, Merlini E, Marchetti G. Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial. PLoS One. 2013 Nov 14;8(11):e80157. doi: 10.1371/journal.pone.0080157. eCollection 2013.