Effects of antiretroviral therapy on proprotein convertase subtilisin/kexin 9: focus on lipids, inflammation and immunovirological parameters.

OBJECTIVES: Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of cholesterol metabolism, have been reported to have an increasing trend in people living with HIV (PLWH) compared with controls. We assessed the impact of different antiretroviral (ARV) regimens on plasma PCSK9 levels as well as plasma lipids, systemic inflammation and immunovirological parameters. METHODS: Eighty HIV-positive ARV therapy (ART)-naïve PLWH and 40 uninfected controls were retrospectively enrolled. At baseline and 3, 6 and 12 months after ART initiation, plasma PCSK9 levels, lipids, high-sensitivity C-reactive protein (hs-CRP), HIV-1 RNA levels and CD4 T-cell count were measured. RESULTS: Baseline PCSK9 levels were significantly more elevated in PLWH and were associated with HIV-1 RNA levels (P < 0.001), CD4 T-cell counts (P < 0.001), triglycerides (P < 0.001) and high-density lipoprotein (HDL) cholesterol (P < 0.001), but not with total cholesterol, low-density lipoprotein (LDL) cholesterol and lipoprotein(a) levels. The prescription of ART was paralleled by significant decreases in plasma PCSK9 and hs-CRP levels, and increases in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and lipoprotein(a), independent of regimen. CONCLUSIONS: PCSK9 levels, along with systemic inflammation, were progressively reduced following the initiation of an effective ART. However, at the end of the study PCSK9 levels remained higher than in controls and did not correlate with any of the lipid variables.

Management of hepatitis B virus reactivation in patients with hematological malignancies treated with chemotherapy.

INTRODUCTION: Hepatitis B virus (HBV) reactivation is a major cause of morbidity and mortality in patients with hematological malignancies who receive cytotoxic chemotherapy. We have therefore carried out a prospective observational study out to assess the incidence, prevalence, and clinical course ina cohort of these patients. METHODS: HBV and HCV markers and liver function indices were monitored prospectively in 318 consecutive patients(171 males, 147 females; mean age 57 years) with hematological malignancies, who had been referred to the Hematology Division, Perugia University, between October 2005 and March 2007 and followed up for at least 6 months. RESULTS: At diagnosis, 32 patients (10%) had received HBV vaccination; 30 were responders. At least one HBV marker was positive in 70/318 patients (22%): 14 (20%) were HBsAg-positive(HBV surface antigen-positive), 13 (19%) were only anti-HBc positive (antibodies to HB core antigen), and 43(61%)were anti-HBc and anti-HBs positive. Twelve HBsAg+ patients received nucleoside/nucleotide analogs (adefovir [six patients],lamivudine [four], and combined adefovir/lamivudine[two non-responders to lamivudine]). After 6 months of therapy, HBV-DNA was negative and transaminases were normal in nine of these 12 patients (adefovir [six], lamivudina[two], adefovir + lamivudina [one]). Seroreversion was achieved in 3/13 patients (23%) who were only anti-HBc positive;all were on rituximab therapy and received adefovir. Seroreversion was not observed in any of the 43 patients who were anti-HBc- and anti-HBs positive. CONCLUSIONS: Essential to the management of patients with hematological malignancies undergoing chemotherapy are surveillance and prophylaxis of HBV infection together with prompt administration of nucleoside/nucleotide analogs in cases of reactivation and/or seroreversion.