Abstract
BackgroundMaraviroc 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 FindingsThirty 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.ConclusionsMaraviroc-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 RegistrationClinicalTrials.gov NCT00098293
Highlights
Decreases in immune activation correlated with increased CD4+ T cell gains
Chronic HIV infection is characterized by persistent immune activation, as measured by CD38 expression on T cells [1,2,3]
As described elsewhere [12], Maraviroc versus Efavirenz Regimens as Initial Therapy (MERIT) evaluated the virologic and immunologic effects of MVC versus EFV, both given with zidovudine/lamivudine, in treatment-naive patients with CCR5tropic (R5) HIV infection
Summary
Chronic HIV infection is characterized by persistent immune activation, as measured by CD38 expression on T cells [1,2,3]. After adequate control of HIV replication, the level of immune activation does not return to the levels observed in uninfected adults [5] This residual heightened T cell surface expression of CD38 has been associated with lower CD4+ T cell gains following highly active antiretroviral therapy (HAART) [5]. In the Strategies for Management of Antiretroviral Therapy (SMART) study, increased levels of the pro-inflammatory cytokine interleukin 6 (IL-6) and of D-dimer, a marker of fibrinolysis, predicted all-cause mortality in persons with treated HIV infection, and impaired liver function among hepatitis coinfected patients [7,8]. 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
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