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

• Published in: PloS one Vol. 5; no. 10; p. e13188
• Main Authors: Funderburg, Nicholas, Kalinowska, Magdalena, Eason, James, Goodrich, James, Heera, Jayvant, Mayer, Howard, Rajicic, Natasa, Valdez, Hernan, Lederman, Michael M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06-10-2010; Public Library of Science (PLoS)
• Subjects: Antiretroviral drugs; Antiviral activity; Benzoxazines - pharmacology; Benzoxazines - therapeutic use; C-reactive protein; Cardiovascular disease; Case-Control Studies; CCR5 protein; CD38 antigen; CD4 antigen; CD4 Lymphocyte Count; CD8 antigen; Cell activation; Cyclohexanes - pharmacology; Cyclohexanes - therapeutic use; Efavirenz; Health risk assessment; HIV; HIV Fusion Inhibitors - pharmacology; HIV Fusion Inhibitors - therapeutic use; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunology/Immunomodulation; Immunology/Leukocyte Activation; Infectious Diseases/HIV Infection and AIDS; Lymphocytes; Lymphocytes T; Markers; Mortality; Patients; Receptors, CCR5 - metabolism; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Ribonucleic acid; RNA; Sensitivity; Statistical analysis; Triazoles - pharmacology; Triazoles - therapeutic use; Viral Load; Cleveland Ohio; New York; Ohio; California; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013188

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.
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.
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.
ClinicalTrials.gov NCT00098293.