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Biomedical subjects

Mao-Yuan Chen

Publications and source records attributed to Mao-Yuan Chen.

At least 19 recordsLinked to original sources

Aberrant induction of regulatory activity of CD4+CD25+ T cells by dendritic cells in HIV-infected persons with amebic liver abscess.

To know why HIV-1-infected persons are particularly susceptible to amebic liver abscess (ALA), we investigated the role of CD4CD25 T cells in the susceptibility of HIV-1-infected persons to this disease. Herein we show, in early stage HIV-1-infected subjects, that CD4 T-cell responses to Entamoeba histolytica antigen (EhAg) were selectively impaired, especially in those with ALA. EhAg-specific CD4 T-cell responses were normalized by depletion of CD4CD25 cells or by addition of anti-cytotoxic T lymphocyte antigen 4 (CTLA4) antibody. Regulatory activity of CD4CD25 T cells to suppress the EhAg-specific CD4 T-cell response could be induced by EhAg-primed dendritic cells (DCs) in HIV-1-infected subjects, especially in those with ALA, but not in healthy controls. Exogenous Tat-incubated DCs derived from HIV-negative subjects also could upregulate CTLA4 expression on autologous CD4CD25 T cells and selectively suppress the EhAg-specific CD4 T-cell response. The results imply an interaction of the two pathogens: HIV-1, perhaps through the effect of Tat on DCs, may upregulate EhAg-specific regulatory T-cell activity to suppress T-cell response to E. histolytica, thus increasing the susceptibility to invasive amebiasis in even early-stage HIV-1-infected persons.

Adult↗

Genetic drift of parvovirus B19 is found in AIDS patients with persistent B19 infection.

It is generally thought that parvovirus B19 is stable genetically. Consistently, genetic drift has not been found in patients with persistent B19 infection. In this report, longitudinal genetic changes in NS1 and VP1 gene of B19 isolates from three AIDS patients with persistent B19 infection were studied. One of the three patients was not treated with highly active anti-retroviral therapy (HAART). B19 viral DNA from these patients was amplified by polymerase chain reaction (PCR) and then sequenced directly. A single genetic change was found in the B19 isolate obtained from the patient not treated with HAART on Day 10 after intravenous immunoglobulin (IVIG) treatment. The nucleotide sequences of B19 isolated from this patient, then remained unchanged over a period of 11 months. Analysis of NS1 clones derived from his longitudinal viral isolates showed the existence of quasi-species but genetic drift was not found. One of the other two patients treated with HAART experienced treatment failure; he was later treated with mega-HAART. In contrast to the genetic stability of B19 isolates from the patient not treated with HAART, multiple genetic changes were discovered in the viral isolates from the two other patients after HAART and mega-HAART, respectively. Through analysis of B19 clones, the frequency of clones containing these mutations confirmed the genetic drift. Nucleotide substitutions seen in VP2 gene of isolates with genetic drift from both patients were all non-conserved, suggesting that they are positively selected.

AIDS-Related Opportunistic Infections↗

Improved survival of persons with human immunodeficiency virus type 1 infection in the era of highly active antiretroviral therapy in Taiwan.

We assessed the survival of 1,044 HIV-infected persons enrolled in three periods: period 1, 1994 to 1997 (before the introduction of highly active antiretroviral therapy [HAART]); period 2, 1997 to 2000 (early-HAART); and period 3, 2000 to 2004 (late-HAART). As of 30 June 2005, 259 (24.8%) persons had died after a median observation duration of 985 days (range, 2 - 4,025 days). The mortality rate declined from 33.75 per 100 person-years in the pre-HAART era to 6.51 per 100 person-years in the late-HAART era (P < 0.0001). The adjusted hazard ratios for death in persons with a baseline CD4 count of <200 cells/mul in periods 2 and 3 were 0.605 (P = 0.007) and 0.371 (P < 0.0001), respectively, when compared with persons enrolled in period 1; the adjusted hazard ratio for death was 0.611 for persons enrolled in period 3 when compared to period 2 (P = 0.01). Our study suggested that the survival of persons in the late stage of HIV infection in Taiwan continued to improve in the late HAART era.

Adolescent↗

Changes in the clinical spectrum of opportunistic illnesses in persons with HIV infection in Taiwan in the era of highly active antiretroviral therapy.

We compared changes in the relative frequencies of opportunistic illnesses (OIs) among 1,044 Taiwanese persons with HIV infection who were enrolled in three study periods from June 1994 to June 2004: before the introduction of highly active antiretroviral therapy (HAART); early HAART; and late HAART. Nearly two-thirds of those newly diagnosed with HIV infection had CD4 counts below 200/mm(3). Among a total of 1,182 OIs, candidiasis, Pneumocystis carinii pneumonia, and tuberculosis were the most common in all three study periods within 3 months after enrollment. Within 3 to 12 months after enrollment, the number of OIs declined significantly. Only 81 cases of OIs were diagnosed, the most common of which were cytomegalovirus disease, tuberculosis, candidiasis, and Mycobacterium avium complex infection. Except for the decreasing frequency of Kaposi's sarcoma, there was no significant change in the relative frequency of each individual OI within 3 months and within 3-12 months after enrollment across the three study periods. We concluded that despite the significant decrease in the number of AIDS-related OIs, the relative frequencies of common OIs did not change significantly after the introduction of HAART.

AIDS-Related Opportunistic Infections↗

Invasive amebiasis as an emerging parasitic disease in patients with human immunodeficiency virus type 1 infection in Taiwan.

BACKGROUND: Whether risk of invasive amebiasis due to Entamoeba histolytica is higher among human immunodeficiency virus (HIV)-infected persons than uninfected persons remains unclear, although intestinal colonization by Entamoeba dispar is common among men who have sex with men. Our objective was to determine the prevalence of invasive amebiasis and intestinal colonization by E histolytica and E dispar in HIV-infected persons and uninfected controls. METHODS: We assessed the prevalence of invasive amebiasis by case review of 951 HIV-infected persons and by serologic studies of 634 of the 951 HIV-infected persons, 429 uninfected controls with gastrointestinal symptoms, and 178 uninfected healthy controls using indirect hemagglutination antibody assay. We assessed the rate of intestinal colonization by E histolytica and E dispar by fecal antigen and polymerase chain reaction tests in 332 asymptomatic HIV-infected persons and 144 of the 178 uninfected healthy controls. RESULTS: Forty-nine (5.2%) of 951 HIV-infected persons had 51 episodes of invasive amebiasis. A high indirect hemagglutination antibody titer was detected in 39 (6.2%) of 634 HIV-infected persons compared with 10 (2.3%) of 429 uninfected controls with gastrointestinal symptoms and 0 of 178 uninfected healthy controls (P<.001). Stool specimens from 40 (12.1%) of 332 HIV-infected persons and 2 (1.4%) of 144 uninfected healthy controls were positive for E histolytica or E dispar antigen (P<.001). Ten (25.0%) of the 40 antigen-positive stool specimens from HIV-infected persons contained E histolytica. CONCLUSION: Persons infected with HIV in Taiwan are at increased risk for invasive amebiasis and exhibit a relatively high frequency of elevated antibody titers and intestinal colonization with E histolytica.

AIDS-Related Opportunistic Infections↗

Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1.

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.

Adaptor Proteins, Signal Transducing↗

Herpes zoster in HIV-1-infected patients in the era of highly active antiretroviral therapy: a prospective observational study.

Between June 1994 and May 2003, 93 of 716 (13.0%) HIV-infected patients with a median baseline cell differentiation CD4+ count of 61 x 10(6) cells/L (range, 1-1206 x 10(6) cells/L) developed 103 episodes of herpes zoster [HZ], with an incidence of 5.67 per 100 person-years (PY). The incidence of HZ in the pre-highly active antiretroviral therapy (HAART) era (17.21 per 100 PY) was significantly higher than that in the post-HAART era (5.05 per 100 PY) (P < 0.0001). In the first six months of enrollment, the incidence of HZ was significantly higher than that between six and 12 months both in the pre-HAART (27.65 per 100 PY versus 8.43 per 100 PY, P = 0.02) and post-HAART era (17.79 per 100 PY versus 3.39 per 100 PY, P < 0.0001). In multivariate analyses, only baseline CD4+ count remained a significant risk factor associated with HZ. HZ did not increase mortality rate either in the pre-HAART or post-HAART era, although the risk for HIV progression was significantly higher in patients with HZ (adjusted odds ratio [OR], 1.747, 95% confidence interval, 1.037-2.943). We conclude that the incidence of HZ was highest in the first six months of enrollment in patients at late stage of HIV infection, which did not increase with the introduction of HAART. Baseline CD4+ lymphocyte count was the most significant risk factor associated with development of HZ. HZ was associated with increased risk for HIV progression, but not mortality.

AIDS-Related Opportunistic Infections↗

Dose reduction for the management of indinavir-related toxicity in human immunodeficiency virus type 1-infected patients in Taiwan: clinical and pharmacokinetic assessment.

This study evaluated the feasibility of reducing the indinavir (IDV) dosage in Taiwanese patients receiving the standard IDV/ritonavir (RTV) dosage of 800/100 mg twice a day who had undetectable plasma human immunodeficiency virus type 1 (HIV-1) RNA but had developed IDV-related toxicities. After dosage reduction to IDV/RTV 600/100 mg twice a day, the dose-related toxicity decreased and plasma HIV RNA remained undetectable at 24 weeks post-switch in all patients. The maximal plasma concentration (Cmax) and area under the plasma concentration-time curve of IDV decreased significantly (median, 6.3 vs 4.3 microg/mL and 1892 vs 1292 microg.min/mL, p=0.01 and 0.001, respectively) but the minimal plasma concentration remained at a similar level (median, 1.0 vs 0.8 microg/mL, p=0.12). This study found that the reduction in the dosage of IDV in HIV-1 infected patients receiving the standard IDV/RTV regimen guided by therapeutic drug monitoring decreased the Cmax, dose-related toxicity and medical cost without compromising viral control.

Acquired Immunodeficiency Syndrome↗

Clinical experience of the 23-valent capsular polysaccharide pneumococcal vaccination in HIV-1-infected patients receiving highly active antiretroviral therapy: a prospective observational study.

To assess the impact of vaccination with 23-valent pneumococcal polysaccharide vaccine on the risks for development of pneumococcal disease, all-cause community-acquired pneumonia, HIV progression, and mortality and immunologic and virologic responses among HIV-1-infected patients treated with highly active antiretroviral therapy (HAART), we conducted a 2-year prospective observational cohort study at a university hospital in Taiwan. A total of 305 HIV-1-infected patients who received 23-valent pneumococcal vaccine (vaccinees) and 203 patients who did not (non-vaccinees) were prospectively observed between 1 June 2000 and 31 October 2002. Changes of CD4+ and plasma viral load (PVL) from baseline to week 4 of vaccination were assessed in 31 randomly selected vaccinees. The incidence of pneumococcal disease and bacteremia of vaccinees was 2.1 per 1000 patient-years (PY) (95% confidence interval (95% CI), 1.7-2.5 per 1000 PY) over the median observation of 641 days (range, 37-832 days) following vaccination while that of non-vaccinee was 21.8 per 1000 PY (95% CI, 20.1-23.7 per 1000 PY) and 7.3 per 1000 PY (95% CI, 7.0-7.6 per 1000 PY), respectively, over the observation of 500 days (range, 32-851 days), with an adjusted odds ratio (AOR) for developing pneumococcal disease of 0.085 (95% CI, 0.010-0.735) and for bacteremia of 0.22 (95% CI, 0.018-2.561). The median CD4+ count increased by 45 x 10(6) l(-1) (P = 0.01) and median PVL change was 0 log(10) copies/ml (range of decrease, -0.74 to 2.47 log(10) copies/ml) after 1 month of pneumococcal vaccination among the subgroup of 31 vaccinees receiving HAART. The median CD4+ count increase from baseline to the end of study was 149 x 10(6) l(-1) for vaccinees and 107 x 10(6) l(-1) for non-vaccinees (P = 0.21). The AOR of developing all-cause community-acquired pneumonia and new AIDS-defining opportunistic illnesses (OI) of vaccinees as compared to non-vaccinees was 1.876 (95% CI, 0.785-4.485) and 0.567 (95% CI, 0.217-1.484), respectively. Death rate of vaccinees and non-vaccinees was 17.7 per 1000 PY (95% CI, 16.5-18.9 per 1000 PY) and 80.5 per 1000 PY (95% CI, 77.1-83.9 per 1000 PY), respectively. Adjusted hazard ratio for death of vaccinees as compared with non-vaccinees was 0.733 (95% CI, 0.236-2.274). Our data suggested that vaccination with 23-valent pneumococcal polysaccharide vaccine and receipt of HAART were associated with reduced risks for pneumococcal disease among HIV-1-infected patients receiving HAART. Vaccination did not increase the risks of all-cause community-acquired pneumonia, HIV progression, and mortality. Vaccination did not increase PVL or decrease CD4+ among HIV-1-infected patients receiving HAART.

Adult↗

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.

Adolescent↗

Voiding dysfunction in women with systemic lupus erythematosus.

OBJECTIVE: We sought to explore bladder dysfunction in a cohort of women with systemic lupus erythematosus (SLE). METHODS: We conducted a prospective study of 152 female patients with SLE during a 15-month period. The clinical status of SLE was determined according to the SLE Disease Activity Index (SLEDAI), and bladder function was evaluated by lower urinary tract symptoms and urodynamic studies. We adapted the American Urological Association (AUA) index questionnaire to assess lower urinary tract symptoms in patients, which were compared with those in 227 age-matched healthy women. RESULTS: The proportion of individuals reporting urinary frequency, urgency, weak urinary stream, and incomplete emptying, as well as severe lower urinary tract symptoms (AUA index score >/=20), was significantly higher in the SLE group when compared with the control group. The AUA index score showed a modest correlation with the SLEDAI score (r = 0.35, P < 0.001) but not with patient age or disease duration. There was a significant relationship between central nervous system involvement and the AUA index score. The most common urodynamic finding was a small cystometric bladder capacity (<150 ml; n = 7 patients), followed by a subnormal urinary flow rate (<12 ml/second; n = 6 patients). In 3 of 7 patients with small cystometric bladder capacities, imaging studies documented a contracted bladder with marked hydroureteronephrosis. CONCLUSION: Patients with SLE experience an increased prevalence of voiding dysfunction compared with healthy individuals. Voiding dysfunction can be attributable to either direct bladder involvement or other disease-related factors.

Adult↗

Is there an ethnic difference in the prevalence of lupus cystitis? A report of six cases.

Lupus cystitis was rare but frequently resulted in obstructive uropathy and had a strong association with gastrointestinal (GI) symptoms. We treated six patients with systemic lupus erythematosus (SLE) and obstructive uropathy from January 1996 to December 2001 in a university hospital. Evidence of cystitis was obtained from cystoscopic biopsy or the presence of thickened bladder wall in image study. Similar to other reports, five patients had GI manifestations such as abdominal pain, nausea/vomiting, diarrhoea or ileus. In addition, mesenteric lymphadenopathy or pancreatitis was noted in three patients. Two patients had been treated for idiopathic thrombocytopenic purpura (ITP), four and 20 years ago, respectively. All six patients had antibodies to double-stranded DNA (dsDNA). Five patients each had antibodies to cardiolipin (IgG aCL) or SSA. The high prevalence of anti-SSA had also been reported in Chinese lupus patients with intestinal pseudo-obstruction, a clinical manifestation frequently associated with bilateral ureterohydronephrosis. Two patients died of intractable infection after the surgical procedures for persistent ureterohydronephrosis and both patients had antibodies to ribosomal P proteins. Lupus cystitis might not be so rare in Chinese patients with SLE. The diagnosis should be kept in mind when lupus patients have urinary and/or GI symptoms.

Adult↗

Discontinuation of secondary prophylaxis in AIDS patients with disseminated non-tuberculous mycobacteria infection.

From June 1994 to June 2002, disseminated infections due to non-tuberculous mycobacteria (NTM) were diagnosed in 42 of 716 (5.9%) non-haemophiliac HIV-infected patients aged > or =15 years who were treated at National Taiwan University Hospital. The median age of these patients was 35 years (range, 27 to 60 years). The median CD4+ cell count and plasma viral load at the time of diagnosis of disseminated NTM infections were 8 x 10(6)/L (range, 0 to 892 x 10(6)/L) and 37,600 copies/mL (range, <400 to >750,000 copies/mL), respectively. The nadir CD4+ count during the observation period was 6 x 10(6)/L (range, 0 to 30 x 10(6)/L). The species of NTM isolated included Mycobacterium avium complex (MAC) [n = 35], Mycobacterium kansasii (4), Mycobacterium chelonae (1), Mycobacterium abscessus (1), and unidentified NTM (3). Co-infection with 2 species of NTM was diagnosed in 2 patients. NTMs were isolated from blood (n = 18), liver (18), lymph node (12), bone marrow (10), cerebral spinal fluid (1), ascites (1), and pericardial effusion (1). The median duration of antimycobacterial therapy of the 42 patients was 7 months (range, 0 to 24 months). Mortality during the study period was greater in the patients enrolled before highly active antiretroviral therapy (HAART) was introduced (14 of 15, 93%) than in those who received HAART (9 of 27, 33%). As of December 31, 2002, 15 patients (35.7%) had discontinued secondary prophylaxis against disseminated NTM infections when their median CD4+ count had increased to 119 x 10(6)/L (range, 25 to 465 x 10(6)/L), and 86.7% (13/15) of the patients had achieved an undetectable plasma viral load after HAART. During the median observation duration of 12 months (range, 2 to 57 months), none of the 15 patients had relapse of disseminated NTM infections. Our findings indicate that disseminated NTM infections without primary prophylaxis were associated with a high mortality rate, especially before HAART became available. In patients who received HAART and had a favorable response with viral suppression and immune restoration, discontinuation of secondary prophylaxis against disseminated NTM infections was safe.

AIDS-Related Opportunistic Infections↗

Successful discontinuation of secondary prophylaxis for histoplasmosis after highly active antiretroviral therapy.

Whether maintenance antifungal prophylaxis against histoplasmosis should be continued life-long in patients with immune restoration after highly active antiretroviral therapy (HAART) remains unclear. We report a case of disseminated histoplasmosis involving the skin, lung, gastrointestinal tract, mesentery, and retroperitoneum in a 33-year-old man with acquired immunodeficiency syndrome. His symptoms improved after use of amphotericin B and itraconazole in addition to ileostomy to relieve the intestinal obstruction. After the start of HAART, he was able to discontinue itraconazole as maintenance therapy without relapse for 24 months.

AIDS-Related Opportunistic Infections↗

Clinical course of children of human immunodeficiency virus-infected mothers in Taiwan.

The objective of this study was to describe the clinical courses of infants born to human immunodeficiency virus (HIV)-infected mothers in Taiwan. Eleven children, including 1 set of twins, born to 10 HIV-infected mothers were included in the study. HIV antibodies were assayed and HIV-1 polymerase chain reaction (HIV-PCR) or virus cultures were performed; HIV infection was established when there were at least 2 separate positive results of HIV-PCR or culture. Three sets of primers detecting LTR-gag, pol and env were used. The viral load of HIV RNA was measured and used as an indicator of the treatment response. Two of the children were HIV-infected and received combination therapy, including 2 kinds of nucleoside analogue reverse transcriptase inhibitors plus 1 protease inhibitor. Neither of these children exhibited HIV-related symptoms or signs during the study period. Both mothers of the infected children were Taiwanese and their HIV infection status was not known during pregnancy. In contrast, HIV infection was found in early pregnancy in the 4 women living in Taiwan who were from other countries, all of whom received prophylactic therapy. The other 4 mothers who did not transmit the infection to the infant were Taiwanese, 3 of whom were known to be HIV-seropositive during pregnancy. Based on these results, the vertical rate of transmission was 18% (2/11). Early detection of HIV-infected pregnancy is vital to reduce the incidence of HIV-infected births.

Anti-HIV Agents↗

Primary adrenal insufficiency in patients with acquired immunodeficiency syndrome: report of four cases.

Adrenal insufficiency, though rare, is a well-known complication of acquired immunodeficiency syndrome (AIDS). Over the past 9 years at the National Taiwan University Hospital, 4 patients were diagnosed with primary adrenal insufficiency among 854 non-hemophiliac patients with human immunodeficiency virus infection, with an incidence of 0.19 per 100 patient-years (95% confidence interval, 0.17-0.21 per 100 patient-years). All of the 4 patients were severely immunosuppressed and had been diagnosed with at least 1 AIDS-defining opportunistic illness ever reported to produce adrenal insufficiency in AIDS patients. In 1 of the patients, fluconazole was considered contributory to the development of adrenal insufficiency after treatment at a daily dose of 800 mg for 68 days.

Acquired Immunodeficiency Syndrome↗