Maraviroc in Immunological Non-Responder (INR) HIV-1-infected Subjects

HIV Infections Clinical Trial

Official title:

Use of Maraviroc (MVC) in Immunological Non-responder HIV-1-infected Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00884858
• Other study ID #: HLS/MVC01/2008
• Status: Completed
• Phase: Phase 4
• First received: April 20, 2009
• Last updated: April 29, 2013
• Start date: April 2009
• Est. completion date: April 2011

Study information

• Verified date: April 2013
• Source: Ospedale L. Sacco – Polo Universitario
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Maraviroc
Maraviroc is administered BID according to the other drugs within HAART; dosage ranges from 150 mg to 600 mg bid.

Locations

Country	Name	City	State
Italy	Divisione di Malattie Infettive, Ospedale S. Maria Annunziata	Antella	FI
Italy	Clinica di Malattie Infettive, Policlinico, Universita' degli Studi	Bari	BA
Italy	Clinica di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Spedali civili	Brescia	BS
Italy	Clinica di Malattie Infettive, Ospedale San Martino	Genova	GE
Italy	Divisione Clinicizzata di Malatie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"	Milano	MI
Italy	I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario Luigi Sacco	Milano	MI
Italy	Polo di Medicina Chirurgia e Odontoiatria, Polo Didattico S. Paolo	Milano	MI
Italy	U.O di Malattie Infettive, Fondazione San Raffaele del Monte Tabor	Milano	MI
Italy	Clinica delle Malattie Infettive, Policlinico Universitario	Modena	MO
Italy	Divisione di Malattie Infettive, Ospedale San Gerardo	Monza	MB
Italy	Divisione Dipartimento Urgenze Infettivologiche ad Alta Complessità e correlate all'AIDS, Ospedale Cotugno	Napoli
Italy	Clinica delle Malattie Infettive, Policlinico Monteluce	Perugia	PG
Italy	U.O. Malattie Infettive, Ospedale S. Spirito	Pescara	PE
Italy	Clinica delle Malattie Infettive, Policlinico "Tor Vergata"	Roma	RM
Italy	III Divisione di Malattie Infettive, I.N.M.I Lazzaro Spallanzani	Roma	RM
Italy	Istituto Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore	Roma	RM
Italy	IV Divisione di Malattie Infettive, INMI Lazzaro Spallanzani	Roma	RM
Italy	U.O. Malattie Infettive, Azienda Policlinico Umberto I	Roma	RM
Italy	Clinica delle Malattie Infettive ,Ospedale Amedeo di Savoia	Torino	TO
Italy	Servizio Regionale di Immunologia Clinica e Tipizzazione Tissutale, Azienda Ospedaliero-Universitaria	Torrette di Ancona	AN

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale L. Sacco – Polo Universitario

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CD4 counts > 200/uL or recovery of CD4 > 25% in 2 consecutive time-points.		3 and 12 months	No