Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients.

Abstract

BACKGROUND:

Maraviroc treatment for HIV-1 infected patients results in larger CD4(+) T cell rises than are attributable to its antiviral activity alone. We investigated whether this is due to modulation of T cell activation and inflammation.

METHODS AND FINDINGS:

Thirty maraviroc-treated patients from the Maraviroc versus Efavirenz Regimens as Initial Therapy (MERIT) study were randomly selected from among those who had CCR5-tropic (R5) HIV on screening and achieved undetectable HIV RNA (<50 copies/mL) by Week 48. Efavirenz-treated controls were matched for baseline characteristics to the maraviroc-treated patients selected for this substudy. Changes in immune activation and inflammation markers were examined for associations with CD4(+) T cell changes. Maraviroc treatment tended to result in more rapid decreases in CD38 expression on CD4(+) T cells and in plasma D-dimer concentrations than did treatment with efavirenz. The proportion of patients with high-sensitivity C-reactive protein >2 µg/mL increased from 45% to 66% in the efavirenz arm, but remained constant in the maraviroc arm (P = 0.033). Decreases in CD38 expression on CD8(+) T cells were correlated with CD4(+) T cell rises for maraviroc treatment (r = -0.4, P = 0.048), but not for treatment with efavirenz.

CONCLUSIONS:

Maraviroc-treated patients had earlier, modest decreases in certain markers of immune activation and inflammation, although in this small study, many of the differences were not statistically significant. Levels of high-sensitivity C-reactive protein remained constant in the maraviroc arm and increased in the efavirenz arm. Decreases in immune activation correlated with increased CD4(+) T cell gains.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00098293.

• Authors: Nicholas Funderburg, Magdalena Kalinowska, James Eason, James Goodrich, Jayvant Heera, Howard Mayer, Natasa Rajicic, Hernan Valdez, Michael M Lederman
• Journal: PloS one (PLoS One) Vol. 5 Issue 10 Pg. e13188 (Oct 06 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20949133 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Benzoxazines
• Cyclohexanes
• Cyclopropanes
• HIV Fusion Inhibitors
• Receptors, CCR5
• Reverse Transcriptase Inhibitors
• Triazoles
• efavirenz
• Maraviroc

Topics

• Alkynes
• Benzoxazines (pharmacology, therapeutic use)
• CD4 Lymphocyte Count
• Case-Control Studies
• Cyclohexanes (pharmacology, therapeutic use)
• Cyclopropanes
• HIV Fusion Inhibitors (pharmacology, therapeutic use)
• HIV Infections (drug therapy, immunology)
• Humans
• Maraviroc
• Receptors, CCR5 (metabolism)
• Reverse Transcriptase Inhibitors (pharmacology, therapeutic use)
• Triazoles (pharmacology, therapeutic use)
• Viral Load