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Anu Osinusi,
Joseph J Rasimas, Rachel Bishop,
Michael Proschan,
Mary McLaughlin,
Alison Murphy,
Karoll J Cortez,
Michael A Polis,
Henry Masur,
Donald Rosenstein,
Shyam Kottilil
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ABSTRACT: This study aimed to assess the relationship between interferon (IFN)-related adverse effects and Hepatitis C virus (HCV) virologic response in HIV/HCV-coinfected individuals treated with pegylated interferon and ribavirin.
We conducted 2 prospective, open-label trials treating HIV/HCV-coinfected individuals with pegylated interferon alpha-2b or alpha-2a and ribavirin for 48 weeks. Safety laboratories, HCV RNA, psychiatric, and ophthalmologic evaluations were performed at baseline and monthly until week 72.
Responders were defined as those with HCV RNA decline of > or = 2-log drop from baseline and nonresponders were those who did not. Remarkably, of the 27 patients (50%) who developed psychiatric toxicities, 26 patients were responders, although only 1 of 14 virologic nonresponders experienced psychiatric toxicity. Other adverse effects, such as anemia and ophthalmologic toxicities, were also more frequent in responders compared with nonresponders. Decline in CD4 T-cell counts strongly correlated with HCV viral decline.
Our study demonstrates coupling of antiviral effect and occurrence of adverse events in HIV/HCV-coinfected patients. These patients with IFN-related adverse effects need a multidisciplinary treatment approach, hence, they are more likely to achieve sustained virologic response. Future studies are needed to evaluate the factors that predict the development of IFN-alpha-dependent adverse events before therapy.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2010; 53(3):357-63. · 4.43 Impact Factor
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Brian O Porter,
G Laissa Ouedraogo,
Jessica N Hodge,
Margo A Smith,
Alice Pau,
Gregg Roby,
Richard Kwan, Rachel J Bishop,
Catherine Rehm,
JoAnn Mican,
Irini Sereti
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ABSTRACT: Biomarkers could be useful in evaluating immune reconstitution inflammatory syndrome (IRIS). A cohort of 45 HIV-1-infected, antiretroviral treatment (ART)-naive patients with baseline CD4 T cell counts <or=100 cells/microL who were started on ART, suppressed HIV-RNA to <50 copies/mL, and seen every 1-3 months for 1 year were retrospectively evaluated for suspected or confirmed IRIS. d-Dimer, C-reactive protein (CRP), and selected autoantibodies were analyzed at baseline, 1 and 3 months post-ART in cryopreserved plasma. Median differences between cases and controls were compared with Mann-Whitney and Fisher's exact tests. Sixteen patients (35.6%) developed IRIS (median of 35 days post-ART initiation): unmasking=8, paradoxical=7, autoimmune=1. Pre-ART d-dimer and CRP were higher in IRIS cases versus controls (d-dimer: 0.89 mg/L versus 0.66 mg /L, p=0.037; CRP: 0.74 mg/L versus 0.39 mg/L, p=0.022), while d-dimer was higher in unmasking cases at IRIS onset (2.04 mg/L versus 0.36 mg /L, p=0.05). These biomarkers may be useful in identifying patients at risk for IRIS.
Clinical Immunology 03/2010; 136(1):42-50. · 4.05 Impact Factor
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ABSTRACT: The purpose of this study was to report a case of limbal stem cell deficiency (LSCD) after systemic chemotherapy with hydroxycarbamide.
Clinical manifestations and pathology are detailed.
We describe the case of a woman with sickle cell disease, who developed bilateral LSCD after treatment with hydroxycarbamide. Histologic examination confirmed the diagnosis of LSCD, revealing goblet cells, inflammatory cells, deposits of new collagen components, and neovascularization in the peripheral cornea. Matrix metalloproteinase-3, fibronectin, and collagen III were also detected in the lesions.
The systemic use of the antineoplastic drug, hydroxycarbamide, may cause severe LSCD. We recommend that a medication history, including that of cytotoxic drugs, be considered in evaluating LSCD.
Cornea 03/2009; 28(2):221-3. · 1.73 Impact Factor
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ABSTRACT: The purine analogs, fludarabine and cladribine represent an important class of chemotherapy agents used to treat a broad spectrum of lymphoid malignancies. Their toxicity profiles include dose-limiting myelosuppression, immunosuppression, opportunistic infection and severe neurotoxicity. This review summarizes the neurotoxicity of high- and standard-dose fludarabine, focusing on the clinical and pathological manifestations in the eye. The mechanisms of ocular toxicity are probably multifactorial. With increasing clinical use, an awareness of the neurological and ocular vulnerability, particularly to fludarabine, is important owing to the potential for life- and sight-threatening consequences.
Expert Review of Ophthalmology 03/2008; 3(1):97-109.
