EACS 2011: Does Maraviroc Intensification Promote Better CD4 Cell Recovery?

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Adding maraviroc (Selzentry or Celsentri) to a suppressive antiretroviral regimen may help promote CD4 T-cell recovery in a subset of patients who experience poor immunological response to treatment, according to 2 studies presented at the 13th European AIDS Conference (EACS 2011) this month in Belgrade.

Some individuals taking antiretroviral therapy (ART) experience smaller-than-expected CD4 cell gains despite maintaining undetectable HIV viral load. The reason for poor CD4 cell recovery is not well understood, nor is there definitive therapy to raise CD4 counts.

French Study

In the first report, Lise Cuzin and fellow investigators with the French ANRS 145 Marimuno study team conducted a pilot study of maraviroc intensification in patients with insufficient immune restoration on ART.

The study included 57 participants with CD4 counts below 350 cells/mm3 and gains of less than 50 cells/mm3 per year, despite being on ART with a stable undetectable viral load (< 50 copies/mL) for at least 2 years.

Almost all were men and the median age was 51 years. They had been infected with HIV for a median of about 12 years and on combination ART for 10 years. The median current CD4 count was 238 cells/mm3, but the median nadir (lowest-ever level) of 61 cells/mm3 reflected a history of severe immune deficiency. Approximately half had exclusively CCR5-tropic HIV while the rest had dual/mixed tropism virus (able to use both CCR5 and CXCR4 coreceptors).

All patients added maraviroc to their stable regimen for 24 weeks, with doses adjusted to compensate for expected drug-drug interactions. Each patient acted as his or her own control.

Results

Based on these findings, the researchers concluded, "In this study, intensification of stable HAART with a 24 weeks course of maraviroc was able to enhance CD4 cells recovery in a subgroup of patients with insufficient immune restoration despite long term non-detectable viral load."

Italian Study

Stefano Rusconi and colleagues with the HSL/MVC01/2008 study group conducted a maraviroc intensification study looking at 96 patients at 21 centers in Italy who experienced rapid HIV RNA suppression (< 50 copies/mL) on ART but poor immune reconstitution. Again most were men, with a median age of about 48 years.

This study was randomized, with half of participants adding maraviroc and the other half staying on their stable baseline suppressive ART regimen. By chance, the median baseline CD4 count was slightly higher in the maraviroc arm than in the stable ART arm (190 vs 170 cells/mm3). Follow-up continued for 48 months.

Results

The researchers concluded that maraviroc was not superior to stable ART overall, but did appear to show a benefit for the simple CD4 count > 200 cells/mm3 endpoint, and for some patients.

They noted that maraviroc reduced activation and proliferation of T-cells, which might indicate that it has an effect on pro-inflammatory status. They added that the transitory reduction of activated CD4 cells accompanied by a rise in plasma IL-7 levels suggests a possible role of maraviroc in sustaining peripheral T-cell homeostasis.

Following the presentation, Peter Hunt from the University of California at San Francisco pointed out that a prior maraviroc intensification study by his group showed increased CD8 activation, while both of the later studies showed a decrease, indicating that further research is needed in this area.

Investigator affiliations:

Abstract PS1/6: Infectious Diseases, Hopital Purpan, Toulouse, France; INSERM U943, University Pierre and Marie Curie, Paris, France; Immunology Laboratory, Paris, France; INSERM UMR S945, UPMC Paris 6, Paris, France; INSERM UMR 1043, Toulouse, France, 6Infectious Diseases, Nimes, France; Infectious Diseases, Montpellier, France; Infectious Diseases, Nantes, France; Clinical

Pharmacy Department, Paris, France; EA449 Paris 7 University, Paris, France; Infectious Diseases, Kremlin Bicêtre, France; Infectious Diseases, Paris, France; CNRS UPR 1142, Human Genetic Institute, Montpellier, France; Immunological Unit, Nimes, France; INSERM U943, Paris, France.

Abstract PS1/7: Sezione di Malattie Infettive e Immunopatologia, Dipartimento di Scienze Cliniche, Milano, Italy; ITB-CNR, Segrate, Italy; Clinica Malattie Infettive, Università degli Studi di Brescia, Spedali Civili, Brescia, Italy; Div. Malattie Infettive, Ospedale Luigi Sacco, Milano, Italy; Div. Malattie Infettive, Ospedale di Circolo, Busto Arsizio (VA), Italy; Clinica Malattie Infettive, Università degli Studi di Torino, Torino, Italy; Clinica di Malattie Infettive, Ospedale Policlinico di Bari, Bari, Italy; Clinica Malattie Infettive, Università degli Studi di Genova, Ospedale San Martino, Genova, Italy; Div. Malattie Infettive, Ospedale S. Maria Annunziata, Antella-Firenze, Italy; Servizio Regionale di Immunologia Clinica e Tipizzazione Tessutale, Università Politecnica delle Marche, Torrette di Ancona, Italy; Div. A Malattie Infettive, Ospedale Amedeo di Savoia, Torino, Italy; Istituto di Clinica Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy; Div. Malattie Infettive, Ospedale Policlinico Umberto I, Roma, Italy; Clinica di Malattie Infettive, Ospedale S. Maria della Misericordia, Perugia, Italy; Div. Malattie Infettive, Ospedale San Gerardo, Monza, Italy; Div. Malattie Infettive, Ospedale Santo Spirito, Pescara, Italy; Clinica Malattie Infettive, Università Tor Vergata, Roma, Italy; INMI “Lazzaro Spallanzani”, IV Div. Malattie Infettive, Roma, Italy; INMI “Lazzaro Spallanzani”, III Div. Malattie Infettive, Roma, Italy; Clinica Malattie Infettive e Tropicali, Università degli Studi di Milano, Ospedale San Paolo, Milano, Italy.

10/25/11

References

L Cuzin, S Trabelsi, G Mouillot L et al. ANRS 145 Marimuno Study: a Multi-centre Prospective Pilot Study Evaluating Intensification of Stable Antiviral Therapy with Maraviroc in HIV-1-infected Patients with Insufficient Immune Restoration Despite Persistently Controlled Viral Replication.13th European

AIDS Conference (EACS 2011). Belgrade, October 12-15, 2011. Abstract PS1/6.

 

S Rusconi, E Colella, F Adorni et al. ANRS 145 Maraviroc (MVC) as Intensification Strategy in Immunological Non-responder HIV-infected Patients with Virologic Success on HAART.13th European AIDS Conference (EACS 2011). Belgrade, October 12-15, 2011. Abstract PS1/7.