Rudi Wisaksana

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 Coxs 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.

The effect of HIV infection on adult meningitis in Indonesia: a prospective cohort study.

Objective:Indonesia has a concentrated but rapidly growing HIV epidemic. We examined the effect of HIV on causative organisms, clinical features and prognosis of adult meningitis. Design:A prospective cohort study. Methods:All adult patients at a referral hospital who underwent cerebrospinal fluid examination for suspected meningitis were examined for HIV and included in a prospective cohort study. Microbiological testing was done for common bacterial pathogens, mycobacteria and fungi. Patients were followed for at least 6 months, and logistic regression models were used to identify risk factors for mortality. Results:Among 185 patients who mostly presented with subacute meningitis, 60% were male and the median age was 30 years. HIV infection was present in 25% of the patients; almost two-thirds were newly confirmed, and all presented with severe immunosuppression (median CD4 cell count 13/μl, range 2–98). One-third of HIV-infected patients had cryptococcal meningitis whereas two-thirds suffered from tuberculosis. After 1 month, 41% of patients had died. HIV infection was strongly associated with 1-month mortality (adjusted odds ratio 12.15; 95% confidence interval 3.04–15.72) and death during extended follow-up (hazard ratio 2.48; 95% confidence interval 1.97–5.74). Conclusion:Although HIV is still uncommon in the general population in Indonesia, its prevalence among adult meningitis cases already seems high. Mycobacterium tuberculosis and Cryptococcus neoformans are the main causes of meningitis in this setting, and mortality is very high, especially in HIV-infected patients. Our data suggest that adult meningitis cases in Indonesia should be screened routinely for HIV infection. Further studies are needed to address the high mortality.

Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia

Background HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis, but often no etiology can be established. In the absence of CT or MRI of the brain, toxoplasmosis is generally not considered as part of the differential diagnosis. Methodology/Principal Findings We performed cerebrospinal fluid real time PCR and serological testing for Toxoplasma gondii in archived samples from a well-characterized cohort of 64 HIV-infected patients presenting with subacute meningitis in a referral hospital in Indonesia. Neuroradiology was only available for 6 patients. At time of presentation, patients mostly had newly diagnosed and advanced HIV infection (median CD4 count 22 cells/mL), with only 17.2% taking ART, and 9.4% PJP-prophylaxis. CSF PCR for T. Gondii was positive in 21 patients (32.8%). Circulating toxoplasma IgG was present in 77.2% of patients tested, including all in whom the PCR of CSF was positive for T. Gondii. Clinically, in the absence of neuroradiology, toxoplasmosis was difficult to distinguish from tuberculosis or cryptococcal meningitis, although CSF abnormalities were less pronounced. Mortality among patients with a positive CSF T. Gondii PCR was 81%, 2.16-fold higher (95% CI 1.04–4.47) compared to those with a negative PCR. Conclusions/Significance Toxoplasmosis should be considered in HIV-infected patients with clinically suspected subacute meningitis in settings where neuroradiology is not available.

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/mm3 (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

BackgroundAnemia 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.MethodsPatient 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 Coxs regression were used to assess factors affecting survival. Logistic regression was used to identity parameters associated with high ferritin concentrations.ResultsAnemia 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.ConclusionHIV-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.

Injecting drug use is associated with a more rapid CD4 cell decline among treatment naive HIV-positive patients in Indonesia

It remains unclear whether the natural course of human immunodeficiency virus (HIV) differs in subjects infected through injecting drug use (IDU) and no data have been published from low‐ or middle‐income countries. We addressed this question in an urban cohort in Indonesia, which is experiencing a rapidly growing HIV epidemic strongly driven by IDU.

Costs and outcomes of VCT delivery models in the context of scaling up services in Indonesia

Objective  To evaluate costs and outcomes of voluntary counselling and testing (VCT) service delivery models in urban Indonesia.

Normal free interleukin-18 (IL-18) plasma levels in dengue virus infection and the need to measure both total IL-18 and IL-18 binding protein levels

ABSTRACT Activated monocytes/macrophages and T lymphocytes that produce a cytokine storm are assumed to play a pivotal role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine that is increased during dengue and known to induce gamma interferon (IFN-γ), which is crucial for dengue immune response. No data are available regarding the balance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) and how they interact within the inflammatory reaction of patients with dengue virus infections. Circulating levels of IL-18; IL-18BP; free, biologically active IL-18; the IL-18-dependent proinflammatory cytokine IFN-γ; monocyte-derived cytokines; and ferritin were assessed in adult Indonesian dengue patients (n = 95). Healthy individuals (n = 22) and leptospirosis (n = 19) and enteric fever (n = 6) patients served as controls. Total IL-18 levels were increased during dengue, leptospirosis, and enteric fever compared to healthy controls. However, due to a concurrent increase in IL-18BP levels, biologically active IL-18 levels remained similar in the different phases of dengue and in patients with leptospirosis. Biologically active IL-18 levels were also similar in patients with severe and nonsevere dengue. In conclusion, high total IL-18 and IL-18BP levels concur in dengue virus infections, leptospirosis, and enteric fever. This resulted in unchanged levels of free, biologically active IL-18 in dengue and leptospirosis, which underlines the importance of measuring both IL-18 and IL-18BP when studying the role of IL-18 in diseases.

Virological failure and drug resistance during first line anti‐retroviral treatment in Indonesia

The virological response and development of drug resistance during first‐line anti‐retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of drug‐resistance. As many as 575 patients starting ART between September 2007 and March 2010 in Hasan Sadikin Hospital Bandung were followed prospectively. Clinical and laboratory monitoring was performed every 6 months. Plasma samples with HIV‐RNA ≥400 copies/ml were examined for drug resistance mutations. Most patients were male (72.3%), 59.7% had a history of injecting drug use, and the median CD4+ cells count before start of ART was 35 cells/mm3 (IQR 10–104). From 438 HIV patients with HIV‐RNA measurements, 40 (9.1%) subjects had HIV‐RNA ≥400 copies/ml after 24 weeks (median follow‐up 16 (IQR 8–25) months). Of these failing patients 16 (47%) subjects had drug resistance mutations, predominantly M184V (35.3%), Y181C (23.5%), K103N (11.7%), and TAMs (11.7%). A history of treatment discontinuation ≥1 month, reported by 5.3% (23) of patients, was strongly associated with virological failure (adjusted OR 12.64, 95% CI 4.51–35.41); and a history of injecting drug use was not (OR 0.75, 95% CI 0.38–1.46). This is the largest and most systematic evaluation of virological response to first line ART in Indonesia. Patients in this cohort responded well to first line ART, with low rates of virological failure and drug resistance. A history of injecting drug use should not be a reason to withhold ART in this setting. J. Med. Virol. 85:1394–1401, 2013.

Hepatitis B virus prevalence, risk factors and genotype distribution in HIV infected patients from West Java, Indonesia.

BACKGROUND Indonesia currently faces both an increasing HIV incidence and a high hepatitis B virus (HBV) burden. OBJECTIVE The objective of our study is to examine the prevalence, risk factors, and genotypic distribution of HBV infection among HIV infected patients in West Java, Indonesia. STUDY DESIGN A cross sectional study was conducted among a cohort of HIV infected patients in 2008. Demographic and disease related variables were compared between HBV negative and positive patients. Logistic regression was applied to determine risk factors for HBV co-infection. HBV and HIV genotyping was performed in co-infected patients. RESULTS Of 636 HIV-infected patients, the rate of HBV co-infection was 7%. The proportion of males was higher in HBV/HIV co-infected patients than in HIV mono-infected patients (93% vs. 72%, P=0.001). A history of injecting drug use (IDU), but not tattooing, was associated with HBV co-infection [P=0.035 OR 2.41 (95% CI 1.06-5.47)]. In the HIV and HBV treatment naive patients, CD4 cells counts <50cells/mm(3), HIV-RNA plasma ≥10,000copies/ml and AST level above normal were more often found in patients with high HBV-DNA levels (≥20,000IU/ml) as compared to those with low HBV DNA (<20.000IU/ml) (P<0.05). As in the general population, B3 was the dominant subtype in HBV co-infected patients. CONCLUSION The prevalence of active HBV infection and the genotype distribution among HIV infected individuals is similar to the overall population in Java. However, an increased prevalence was observed in men with a history of IDU, underlining the need for routine HBV screening and monitoring.