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


RESULTS
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.


BACKGROUND
ClinicalTrials.gov NCT00098293.
Case Western Reserve University, Cleveland, Ohio, United States of America.
Nicholas
N
Funderburg
Magdalena
M
Kalinowska
James
J
Eason
James
J
Goodrich
Jayvant
J
Heera
Howard
H
Mayer
Natasa
N
Rajicic
Hernan
H
Valdez
Michael M
MM
Lederman
D000480:Alkynes; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use; D003521:Cyclopropanes; D023581:HIV Fusion Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D000077592:Maraviroc; D019713:Receptors, CCR5 / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D019562:Viral Load
D000480:Alkynes; D048588:Benzoxazines; D003510:Cyclohexanes; D003521:Cyclopropanes; D023581:HIV Fusion Inhibitors; D019713:Receptors, CCR5; D018894:Reverse Transcriptase Inhibitors; D014230:Triazoles; C098320:efavirenz; D000077592:Maraviroc