Inverse relationship of serum hepcidin levels with CD4 cell counts in HIV-infected patients selected from an Indonesian prospective cohort study.

BACKGROUND: Distortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB. METHODS: Three groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia. The first group consisted of HIV-infected patients who started TB treatment more than 30 days after cohort enrollment (cases). The second group consisted of HIV-infected patients who were matched for age, gender and CD4 cell count to the cases group (matched controls). The third group consisted of HIV-infected patients with CD4 cell counts above 200 cells/mm(3) (unmatched controls). Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin. RESULTS: A total of 127 HIV-infected patients were included, 42 cases together with 42 matched controls and 43 unmatched controls. Patients with advanced HIV infection had elevated serum hepcidin and ferritin levels. Hepcidin levels correlated inversely with CD4 cells and hemoglobin. Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment. Hepcidin levels were not different in those with or without hepatitis C infection. CONCLUSION: Iron metabolism is distorted in advanced HIV infection with CD4 cell counts correlating inversely with serum hepcidin levels. High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients.

Anemia and iron homeostasis in a cohort of HIV-infected patients in Indonesia.

BACKGROUND: Anemia is a common clinical finding in HIV-infected patients and iron deficiency or redistribution may contribute to the development of low hemoglobin levels. Iron overload is associated with a poor prognosis in HIV and Hepatitis C virus infections. Iron redistribution may be caused by inflammation but possibly also by hepatitis C co-infection. We examined the prevalence of anemia and its relation to mortality in a cohort of HIV patients in a setting where injecting drug use (IDU) is a main mode of HIV transmission, and measured serum ferritin and sTfR, in relation to anemia, inflammation, stage of HIV disease, ART and HCV infection. METHODS: Patient characteristics, ART history and iron parameters were recorded from adult HIV patients presenting between September 2007 and August 2009 in the referral hospital for West Java, Indonesia. Kaplan-Meier estimates and Cox's regression were used to assess factors affecting survival. Logistic regression was used to identity parameters associated with high ferritin concentrations. RESULTS: Anemia was found in 49.6% of 611 ART-naïve patients, with mild (Hb 10.5 -12.99 g/dL for men; and 10.5-11.99 g/dL for women) anemia in 62.0%, and moderate to severe anemia (Hb < 10.5 g/dL) in 38.0%. Anemia remained an independent factor associated with death, also after adjustment for CD4 count and ART (p = 0.008). Seroprevalence of HCV did not differ in patients with (56.9%) or without anemia (59.6%). Serum ferritin concentrations were elevated, especially in patients with anemia (p = 0.07) and/or low CD4 counts (p < 0.001), and were not related to hsCRP or HCV infection. Soluble TfR concentrations were low and not related to Hb, CD4, hsCRP or ART. CONCLUSION: HIV-associated anemia is common among HIV-infected patients in Indonesia and strongly related to mortality. High ferritin with low sTfR levels suggest that iron redistribution and low erythropoietic activity, rather than iron deficiency, contribute to anemia. Serum ferritin and sTfR should be used cautiously to assess iron status in patients with advanced HIV infection.

Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia.

BACKGROUND: There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. METHODS: Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan-Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. RESULT: A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12-111] cells/mm(3) compared to 84 (IQR, 28-224) cells/mm(3) in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts <25, 25-99, 100-199, respectively, > or =200/mm(3) had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35-1.23], loss to follow-up (HR = 0.85, 95% CI 0.51-1.41) and virological failure (HR = 0.47, 95% CI 0.19-1.13) were not significantly different in IDUs and non-IDUs. CONCLUSION: Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy.

Challenges in delivering HIV-care in Indonesia: experience from a referral hospital.

HIV in Indonesia is strongly associated with injecting drug use (IDU), and surrounding stigma and lack of knowledge reduce accessibility of services. Uptake of HIV-testing is low and many patients present with advanced AIDS. A comprehensive evaluation was made of HIV-services provided between 2006 and 2008 in a referral hospital in West-Java, the province with the highest burden of HIV in Indonesia. A total of 826 HIV-positive patients, mostly infected through IDU (73.9%), presented between 2006 - 2008. Targeted screening and provider-initiated testing and counseling (PITC) led to earlier HIV-diagnosis. Operational research helped optimize diagnosis and treatment of important disease complications. Systematic monitoring of treatment response, and collaboration with other providers, methadone maintenance program and prison help improve treatment outcome. Over the last three years, the number of individuals tested and treated for HIV increased approximately two-fold and six-month mortality decreased from 13.6% to 7.5%. Loss to follow-up was 12.2% at six months. Significant progress has been made in delivering HIV-care in West-Java through operational research, systematic treatment monitoring, and the use of simple indicators to evaluate the quantity and quality of care.

Deep vein thrombosis in acute myelogenous leukemia.

Thrombotic complications in acute leukemia are often underestimated because bleeding complications generally dominate the clinical picture. While there are many thrombogenic factors shared by both solid tumors and leukemia, many additional prothrombotic features are present in leukemia. The prothrombotic factors include hyperleukocytosis, increased expression of tissue factor and its activation in leukemic cells, and the prothrombotic adverse effects of therapeutic agents and vascular access cathethers. A 18-year old woman came with swelling on her right leg 10 days before hospital admission. Since 2 months before she had had weakness, pallor and fever without bleeding manifestation. Hematologic examinations showed anemia, leukocytosis with monoblast and thrombocytopenia. Deep vein thrombosis in right femoral and right popliteal vein was confirmed using compression ultrasonography. The treatment of such complications is challenging because of the high risk of hemorrhage in this group of patients, especially due to their severe thrombocytopenia.

Gene rearrangements in follicular lymphoma among Indonesian.

AIM: Gene rearrangement has an important role in the management of lymphoma. We investigated the rearrangements of B-cell leukaemia/lymphoma 2 (BCL2), BCL6 and Paired homeobox 5 (PAX5) genes in Indonesian follicular lymphoma (FL) patients. METHODS: We examined gene rearrangements using various kinds of polymerase chain reactions (PCRs) on 24 patients' peripheral blood DNA. RESULTS: BCL2 rearrangement was found in 58% (14 of 24 patients), 8 at mbr (major breakpoint region), 2 at mcr (minor cluster region) and 4 at icr (intermediate cluster region), respectively. No rearrangement in BCL6 and PAX5 was detected. There was a significant difference in the incidence of spleen involvement between patients with BCL-2 rearrangement and without it (50% vs. 11%, p=0.04). BCL-2 rearrangement was correlated with spleen involvement (OR=9) and anemia (OR=2.3). CONCLUSION: BCL2 rearrangement in Indonesian FL was higher than previous reports from other Asia countries (58% vs. 48%, respectively). Our method using peripheral blood DNA might be useful for the molecular diagnosis of FL.