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 mg/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 =20.4, 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 highsensitivity 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. © 2010 Funderburg et al.