Mao-Yuan Chen

Impact of Chronic Hepatitis B Virus (HBV) Infection on Outcomes of Patients Infected with HIV in an Area Where HBV Infection Is Hyperendemic

Between June 1994 and February 2003, a total of 111 human immunodeficiency virus (HIV)-infected patients with chronic hepatitis B virus (HBV) coinfection and 387 HIV-infected patients without HBV or hepatitis C virus coinfection were prospectively observed to assess the impact of HBV infection on outcomes of HIV-infected patients. After a median duration of observation of 25 months, coinfected patients were more likely to develop hepatitis (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [CI], 1.69-3.82) and hepatic decompensation (adjusted odds ratio [AOR], 9.94; 95% CI, 1.89-52.35). Although similar proportions of the 2 patient groups had an increase in the CD4 count by > or =100x10(6) cells/L (AOR, 0.78; 95% CI, 0.45-1.36) and development of new opportunistic illnesses (AOR, 0.94; 95% CI, 0.53-1.66), HBV-infected patients had an increased risk for virologic failure (AOR, 1.76; 95% CI, 1.03-2.99) and death (AHR, 1.71; 95% CI, 1.19-2.47) after highly active antiretroviral therapy was initiated.

Human Immunodeficiency Virus Type 1 Vpr Interacts with Antiapoptotic Mitochondrial Protein HAX-1

ABSTRACT Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death. Conversely, overexpression of HAX-1 suppressed the proapoptotic activity of Vpr.

Evolution of Hepatitis B Serological Markers in HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy

BACKGROUND Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers. RESULTS After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively. CONCLUSIONS Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.

Invasive amoebiasis: an emerging parasitic disease in patients infected with HIV in an area endemic for amoebic infection.

OBJECTIVES To describe the incidence and presentations of invasive amoebiasis (IA) in patients with HIV infection in an area endemic for amoebic infection and to assess the role of the indirect haemagglutination (IHA) assay in the diagnosis of IA in HIV-infected patients. DESIGN Retrospective study of 18 cases of IA and HIV infection. SETTING A university hospital, the largest centre for management of HIV-associated complications in Taiwan. METHODS Medical, microbiological and histopathological records of 296 HIV-infected patients and serological data of IHA assay of 126 HIV-infected patients were reviewed to identify cases of IA from 23 June 1994 to 31 March 1999. An IHA titre > or = 1 : 128 was considered positive. Clinical characteristics of HIV-infected patients with IA and without IA were compared. RESULTS Eighteen of the 296 patients (6.1%) with HIV infection were diagnosed with IA: 12 patients were diagnosed with definite IA and six with probable IA. The clinical manifestations included amoebic colitis (13 patients), amoebic liver abscess (nine), both colitis and abscess (four), and pleural effusion (two). IA was the initial presentation of HIV infection in nine patients. Co-infection with other enteric pathogens was diagnosed in six patients with IA. Compared with the 161 patients without IA who were newly diagnosed with HIV infection, the nine patients with IA had a higher median CD4+ lymphocyte count (202 x 10(6)/l versus 33 x 10(6)/l; P = 0.0017), were less likely to be diagnosed with AIDS (55.6% versus 85.4%; P = 0.039), and had fewer concurrent AIDS-defining illnesses (median number 0 versus 2; P = 0.003). Estimated mean survival duration was not significantly different between the two groups (597 days versus 611 days). Fourteen out of 126 patients (11.1%) had an IHA titre > or = 1 : 128. Of the 18 patients diagnosed with IA, 13 had a titre > or = 1 : 128. The sensitivity of IHA assay in the diagnosis of IA was 72.2% (13 out of 18) and the specificity was 99.1% (107 out of 108). The positive predictive value of IHA test for IA of this patient population was 92.9% (13 out of 14) whereas the negative predictive value was 95.5% (107 out of 112). CONCLUSION IA is an increasingly important parasitic disease among patients with HIV infection in Taiwan. IHA assay has a good specificity and high negative predictive value in diagnosis of IA.

Impact of Hepatitis D Virus Infection on the Long-Term Outcomes of Patients with Hepatitis B Virus and HIV Coinfection in the Era of Highly Active Antiretroviral Therapy: A Matched Cohort Study

BACKGROUND Triple infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis D virus (HDV) is rare. The influence of HDV infection on the responses to highly active antiretroviral therapy and hepatic complications in patients with HBV-HIV coinfection remains uncertain. METHODS Twenty-six HDV-infected case patients and 78 HDV-uninfected matched control subjects were identified between 1 January 1995 and 30 June 2003. Clinical and immunologic outcomes were noted, and HBV and HIV loads and genotypic resistance of HBV to lamivudine were determined. RESULTS Case patients had a higher rate of injection drug use (7.7% vs. 1.3%; P=.05) and lower serum levels of HBV DNA (median level, 4.04 vs. 5.75 log10 copies/mL; P=.07) than control subjects. During a median observation period of 54.7 months, HDV infection did not have an adverse impact on clinical, virological, or immunologic responses to highly active antiretroviral therapy. However, case patients had higher rates of hepatitis flares (57.7% vs. 23.1%; P=.002), hyperbilirubinemia (34.6% vs. 14.1%; P=.04), liver cirrhosis (26.9% vs. 5.1%; P=.009), hepatic decompensation (23.1% vs. 5.1%; P=.007), and death (adjusted hazard ratio, 5.41; 95% confidence interval, 1.39-23.85; P=.02), although these patients had a lower risk of genotypic resistance to lamivudine (0% vs. 57.1%; P=.003). CONCLUSIONS HDV infection did not affect clinical, virological, or immunologic responses to highly active antiretroviral therapy in patients with HBV-HIV coinfection. HDV infection increased risk of hepatitis flares, liver cirrhosis, hepatic decompensation, and death in patients with HBV-HIV coinfection.

Clinical spectrum, morbidity, and mortality of acquired immunodeficiency syndrome in Taiwan: a 5-year prospective study.

The clinical spectrum of AIDS and changes of morbidity and mortality associated with HIV infection following initiation of highly active antiretroviral therapy (HAART) are rarely described in the less developed countries in the Asia-Pacific region. We prospectively observed on a follow-up basis 309 HIV-infected patients (82.8% with AIDS) at National Taiwan University Hospital in Taiwan, where highly active antiretroviral therapy (HAART) has been provided to all patients at no charge at any stage of HIV infection since April 1, 1997, to describe the spectrum of HIV-associated opportunistic diseases and evaluate changes of morbidity and mortality from June 24, 1994 through June 23, 1999. Of the patients, 59.3% at study entry had a CD4+ lymphocyte count of <50 cells/microliter. The five leading HIV-associated opportunistic infections included oroesophageal candidiasis (195 patients), Pneumocystis carinii pneumonia (93), tuberculosis (77), mucocutaneous herpes simplex infection (74), and cytomegalovirus diseases (73). The incidence rates of seven major AIDS-defining opportunistic diseases were declining though the changes of the relative proportions varied. The median duration of hospitalization decreased from 36 days in 1995 to 12 days in 1999 (p =.0001). Overestimated mortality rate declined from 148.4 per 100 patient-years in 1995 to 7.4 per 100 patient-years in 1999 (p =.0001) whereas the underestimated mortality rate declined from 110.5 to 5.39 per 100 patient-years (p =.0001). Risk ratio (RR) for mortality in patients who received HAART compared with those who did not was 0.410 (95% confidence interval [CI], 0.249-0.674; p =.0004) and the RR was 0.250 (95% CI, 0.127-0.492; p =.0001) when the analysis was limited to patients with an initial CD4+ lymphocyte count <100 cells/microliter and follow-up duration >30 days after adjusting for their age, gender, type of risk behavior, and CD4+ lymphocyte count. Morbidity and mortality were declining with each study year even in a population consisting mainly of patients at the advanced stage of HIV infection in Taiwan. Earlier diagnosis, accumulation of clinical experience, and use of HAART were associated with lower mortality rates.

Measurement of synovial tumor necrosis factor-alpha in diagnosing emergency patients with bacterial arthritis

Because of the high morbidity and mortality in patients with bacterial arthritis, rapidly and correctly diagnosing this critical condition is a challenge to emergency clinicians. Synovial fluid samples were obtained from 75 patients with arthritis disorders who presented to an emergency service, and levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured. Twenty patients with culture-proven bacterial arthritis had higher levels of synovial TNF-alpha than patients with osteoarthritis or with inflammatory arthritis, including gouty arthritis, rheumatoid arthritis, reactive arthritis, and lupus arthritis. There was a good sensitivity for synovial TNF-alpha level in diagnosing patients with bacterial arthritis. Nearly 100% of patients with bacterial arthritis had elevated synovial TNF-alpha levels. However, synovial IL-1 beta and IL-6 levels failed to discriminate bacterial arthritis from other inflammatory arthritis. Measurement of synovial TNF-alpha level may be useful as a diagnostic aid in emergency patients with bacterial arthritis disorders.

Geographical differences in human herpesvirus 8 seroepidemiology : A survey of 1,201 individuals in Asia

Since the discovery of human herpesvirus 8 (HHV8) as a contributory cause of Kaposis sarcoma, the clinical role of this virus has been actively investigated. An understanding of HHV8 seroepidemiology is critical for the study of its pathogenesis within a specific environment. A sero‐survey is described in Taiwan of 1,201 individuals ranging in age from under 1 year to over 70. Indirect immunofluorescence assay was used to determine antibody titers against both latent and lytic antigens of HHV8. The results indicate that very few individuals (3–4%) were exposed to HHV8 before 10 years of age. Infection rate peaked (19.2%) between the ages of 21 to 40. Females showed a slightly higher seroprevalence for HHV8 than males, but the difference was not statistically significant. Pregnancy did not correlate with increased HHV8 infection rate nor with augmented HHV8 antibody titers. It is concluded that HHV8 in Taiwan is predominantly an infectious agent for adults. In this geographical locale, HHV8 is similar to herpes simplex virus type 2 in its likely transmission occurring presumptively through sexual routes. However, the study also indicates that a smaller portion of HHV8‐transmission could occur through nonsexual contacts. J. Med. Virol. 60:290–293, 2000.

restoration of Cellular Immunity Against Tuberculosis in Patients Coinfected With Hiv-1 and Tuberculosis With Effective Antiretroviral Therapy: Assessment by Determination of Cd69 Expression on T Cells After Tuberculin Stimulation

&NA;Whether immunity against opportunistic pathogens can be fully restored by control of HIV‐1 replication remains open to question. This longitudinal study was conducted to measure anti‐tuberculosis (TB) cellular immunity in 13 HIV‐1/TB‐coinfected patients effectively treated by highly active antiretroviral therapy (HAART) in a period of 12 months. In this study, anti‐TB cellular immunity was assessed by determining the frequencies of CD 69 expression on CD4+ and CD8+ T cells in response to purified protein derivative (PPD) stimulation (abbreviated as %CD4+CD69 to PPD and %CD8+CD69 to PPD). Here, we show that %CD4+CD69 to PPD correlated with the results of tuberculin skin tests and interferon‐&ggr; (IFN‐&ggr;) production from PPD‐stimulated CD4+ T cells, and %CD8+CD69 to PPD also correlated with CD8+T cell‐mediated PPD‐specific cytolysis. In overall analysis for these 13 patients, both %CD4+CD69 to PPD and %CD8+CD69 to PPD increased significantly during the 12 months (p = .003 and p < .001, respectively). However, we found %CD4+CD69 to PPD or %CD8+CD69 to PPD failed to increase substantially in some patients (i.e., immunologic nonresponders). A significantly higher proportion of patients whose baseline CD4+ count was <50 cells/mm3 were considered to be CD4+ nonresponders compared with those whose baseline CD4+ count was >50 cells/mm3. Furthermore, baseline CD4+ cell count in nonresponders is significantly lower than that in responders, although the effectiveness of HAART did not differ between them. Our results indicate that PPD‐specific frequencies of CD69 expression may be used as surrogate markers of anti‐TB cellular immunity. By this method, we show that full reconstitution of anti‐TB cellular immunity in HIV‐1/TB coinfected patients may not necessarily be achieved by “successful” HAART and may be influenced by the baseline immune status when HAART is started. These data suggest that the decision to discontinue secondary prophylaxis for opportunistic infections should be cautiously made, even when the CD4+ cell count has significantly increased.

Admissions to intensive care unit of HIV-infected patients in the era of highly active antiretroviral therapy: etiology and prognostic factors

IntroductionAlthough access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era.MethodsMedical records of all HIV-infected adults who were admitted to ICU at a university hospital in Taiwan from 2001 to 2010 were reviewed to record information on patient demographics, receipt of HAART, and reason for ICU admission. Factors associated with hospital mortality were analyzed.ResultsDuring the 10-year study period, there were 145 ICU admissions for 135 patients, with respiratory failure being the most common cause (44.4%), followed by sepsis (33.3%) and neurological disease (11.9%). Receipt of HAART was not associated with survival. However, CD4 count was independently predictive of hospital mortality (adjusted odds ratio [AOR], per-10 cells/mm3 decrease, 1.036; 95% confidence interval [CI], 1.003 to 1.069). Admission diagnosis of sepsis was independently associated with hospital mortality (AOR, 2.91; 95% CI, 1.11 to 7.62). A hospital-to-ICU interval of more than 24 hours and serum albumin level (per 1-g/dl decrease) were associated with increased hospital mortality, but did not reach statistical significance in multivariable analysis.ConclusionsRespiratory failure was the leading cause of ICU admissions among HIV-infected patients in Taiwan. Outcome during the ICU stay was associated with CD4 count and the diagnosis of sepsis, but was not associated with HAART in this study.