Chin-Fu Hsiao

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.

Increased Risk for Entamoeba histolytica Infection and Invasive Amebiasis in HIV Seropositive Men Who Have Sex with Men in Taiwan

Background Incidence of Entamoeba histolytica infection and clinical manifestations and treatment response of invasive amebiasis (IA) in HIV-infected patients have rarely been investigated before. Methodology/Principal Findings At the National Taiwan University Hospital, medical records of HIV-infected patients who received a diagnosis of IA between 1994 and 2005 were reviewed. The incidence of amebiasis was investigated in serial blood and stool samples from 670 and 264 HIV-infected patients, respectively, using serological and specific amebic antigen assays. DNA extracted from stool samples containing E. histolytica were analyzed by PCR, sequenced, and compared. Sixty-four (5.8%) of 1,109 HIV-infected patients had 67 episodes of IA, and 89.1% of them were men having sex with men (MSM). The CD4 count at diagnosis of IA was significantly higher than that of the whole cohort (215 cells/µL vs. 96 cells/µL). Forty episodes (59.7%) were liver abscesses, 52 (77.6%) colitis, and 25 (37.3%) both liver abscesses and colitis. Fever resolved after 3.5 days of metronidazole therapy (range, 1–11 days). None of the patients died. The incidence of E. histolytica infection in MSM was higher than that in other risk groups assessed by serological assays (1.99 per 100 person-years [PY] vs. 0 per 100 PY; p<0.0001) and amebic antigen assays (3.16 per 100 PY vs. 0.68 per 100 PY; p = 0.12). In multiple logistic regression analysis, only MSM was significantly associated with acquisition of E. histolytica infection (adjusted odds ratio, 14.809; p = 0.01). Clustering of E. histolytica isolates by sequencing analyses from geographically-unrelated patients suggested person-to-person transmission. Conclusions/Significance HIV-infected MSM were at significantly higher risk of amebiasis than patients from other risk groups. Despite immunosuppression, amebic liver abscesses and colitis responded favorably to treatment.

Trends of mortality and causes of death among HIV-infected patients in Taiwan, 1984-2005.

The aim of this study was to analyse the trends of mortality and causes of death among HIV‐infected patients in Taiwan from 1984 to 2005.

Colonization of Human Immunodeficiency Virus-Infected Outpatients in Taiwan with Candida Species

ABSTRACT To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients in Taiwan, we have conducted a prospective cohort study of Candida colonization and its risk factors at the National Taiwan University Hospital from 1999 to 2002. More than 50% of the patients were colonized with Candida species, and 12% developed symptomatic candidiasis. Patients colonized with fluconazole-resistant strains of Candida species had a higher prevalence of candidiasis than those colonized with susceptible strains. Our analysis found that antibiotic treatment and lower CD4+ counts (<200 cells/mm3) increased the rate of oropharyngeal candidiasis in HIV-infected patients, while antiretroviral therapy protected patients from the development of candidiasis.

Correlation Between Bone Mineral Density and Plasma Lipids in Taiwan

Many studies showed that depression is correlated with osteoporosis, while others showed that low cholesterol level is also related to depression. However, these relationships still remain controversial. Since the bone mineral density (BMD) is related to depression and depression is related to hypocholesterolemia, there might exist a correlation between BMD and plasma cholesterol levels. To prove this, we enrolled 5000 individuals, 2170 males, and 2830 females, who had health check‐ups at a private clinic between 1998 and 1999. They were divided into three groups. Group 1 was composed of male subjects; Group 2, female subjects; and Group 3, females aged over 50 to exclude pre‐menopausal females. Each subject had a routine physical examination, fasting blood drawing, BMD measured by dual energy x‐ray absorptiometry (DEXA) over the wrist, and was given a questionnaire to answer. Between Groups 1 and 2, the females were significantly younger, had higher body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), and platelet, but lower BMD, fasting plasma glucose (FPG), triglycerides (TG), hemoglobin (Hgb), and white blood cell (WBC) count. As for Groups 1 and 3, all the aforementioned findings still remained the same except that the systolic blood pressure (SBP) was higher and diastolic blood pressure (DBP) was lower in Group 3. Our results showed that BMD is negatively related to age in males. In females, it is negatively correlated with age, FPG, PPG, SBP, DBP, TC, LDLC, TG, and Hgb, but positively related to BMI and platelet. However, for females in Group 3, BMD is only negatively related to age, FPG, SBP, and TG but positively related to BMI. Stepwise multiple regression analysis showed that the BMD is negatively related to age but positively related to BMI in both males and females. In Group 3, BMD is negatively related to age and FPG but positively related BMI. In conclusion, no correlation exists between BMD and cholesterol. This implies that the depression is not significantly related to cholesterol and/or BMD. This might be due to various confounding factors, which could affect their relationships. The negative correlation between BMD and FPG is only observed in females older than 50 years. Further studies are needed to clarify these relationships.

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.

Risk of Recurrent Nontyphoid Salmonella Bacteremia in HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy and an Increasing Trend of Fluoroquinolone Resistance

BACKGROUND Risk of recurrent nontyphoid Salmonella (NTS) bacteremia and trends of antimicrobial resistance of NTS remain unknown in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS Ninety-three patients who received a diagnosis of NTS bacteremia from June 1994 through June 2006 were prospectively followed up. Incidence of recurrent NTS bacteremia was compared between the pre-HAART era (June 1994-March 1997) and the HAART era (April 1997-June 2006). Prevalence of antimicrobial resistance was compared among the NTS isolates obtained in the pre-HAART era, the early HAART era (April 1997-June 2002), and the late HAART era (July 2002-June 2006). RESULTS Compared with patients enrolled in the pre-HAART era, patients who received HAART had an incidence of recurrent NTS bacteremia that was significantly reduced by 96%; the incidence of recurrent NTS bacteremia was 2.56 cases per 100 person-years in the HAART era, compared with 70.56 cases per 100 person-years in the pre-HAART era (rate ratio, 0.036; 95% confidence interval, 0.012-0.114; P<.001). In the HAART era, the incidence of recurrent NTS bacteremia did not increase among patients receiving fluoroquinolone prophylaxis for <or=30 days (1.69 cases per 100 person-years), compared with among patients receiving fluoroquinolones for >30 days (3.95 cases per 100 person-years), with a rate ratio of 0.43 (95% confidence interval, 0.07-2.58). Although resistance to ampicillin, cotrimoxazole, and chloramphenicol decreased, the proportion of NTS isolates resistant to fluoroquinolones increased from 0% in the pre-HAART era to 6.2% in the early HAART era and 34.2% in the late HAART era (P=.002). CONCLUSIONS The risk of recurrent NTS bacteremia decreased significantly in the HAART era, although NTS isolates obtained from HIV-infected patients were increasingly resistant to fluoroquinolones.

Impact of chronic hepatitis C infection on outcomes of patients with an advanced stage of HIV-1 infection in an area of low prevalence of co-infection

To ascertain whether hepatitis C (HCV) co-infection affects the progression of HIV infection, we initiated an eight-year prospective observational study at a university hospital in Taiwan where seroprevalences of HCV antibody and HIV antibody were low. Fifty-three (12.0%) consecutive non-haemophiliac HIV1-infected patients with HCV co-infection and 387 (88.0%) patients without HCV and hepatitis B co-infection were enrolled between June 1994 and June 2002 and observed until December 2002. Outcomes evaluated included the risk for acute hepatitis, hepatic decompensation, HIV disease progression and mortality, and changes of CD4+ count and plasma viral load (PVL) after initiation of highly active antiretroviral therapy (HAART) at the end of the study. The baseline CD4+ count, PVL and proportion of patients with AIDS-defining opportunistic illnesses (OI) at study entry were similar between patients with HCV co-infection and those without co-infection, but HCV-co-infected patients were older (39 versus 35 years, P = 0.01) and had a higher proportion of intravenous drug use (17.0% versus 0.8%, P < 0.001). After a total observation duration of 1137 patient-years (PY) (median, 791 days; range, 3–3053 days), the incidence of acute hepatitis in HCV-co-infected patients was 13.89 per 100 PY (95% confidence interval [CI], 13.31–14.49) and that in patients without co-infection was 6.39 per 100 PY (95% CI, 6.24–6.55 per 100 PY), with an adjusted odds ratio (OR) of 2.769 (95% CI, 1.652–4.640). At the end of the study, CD4+ count increased by 137 × 106 and 157 × 106/L in patients with and without HCV co-infection, respectively, (P = 0.47). The proportions of achieving undetectable PVL (<400 copies/mL) after HAART was similar (76.7% versus 74.9%, P = 0.79). The adjusted OR for development of new AIDS-defining OI was 1.826 (95% CI, 0.738–4.522) in HCV-co-infected patients as compared with HCV- uninfected patients. The adjusted hazards ratio for death of HCV-co-infected patients when compared with those without co-infection was 0.781 (95% CI, 0.426–1.432). Our findings suggested that HCV co-infection was associated with a significantly higher risk for acute hepatitis in HIV-infected patients receiving antiretroviral therapy, but it had no adverse impact on virological, immunological and clinical responses to HAART and survival when compared with patients without HCV and HBV co-infection.

Discontinuation of secondary prophylaxis for penicilliosis marneffei in AIDS patients responding to highly active antiretroviral therapy.

The studies of the discontinuation of antifungal prophylaxis in HIV-infected patients responding to highly active antiretroviral therapy (HAART) reported to date including the present study all involved small case numbers and short observation durations. In addition unlike the recommendations for the discontinuation of primary or secondary prophylaxis for pneumocystosis no specific cut-off value of CD4 cell count can be used as a clinical guide to discontinue secondary antifungal prophylaxis. Therefore randomized case-control studies are desperately needed to confirm those observations and to set the appropriate cut-off value of CD4 cell count for the discontinuation of secondary antifungal prophylaxis in HIV-infected patients who respond favourably to HAART. (excerpt)

Prevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis in non-haemophiliac HIV-1-infected adults in Taiwan

We assessed the seroprevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis (TE) in 844 non-haemophiliac HIV-infected patients in Taiwan between June 1994 and April 2003. Approximately 70% (69.3%) of them had a baseline CD4+ lymphocyte count of 200 × 106/L or less, and more than 70% (73.9%) having initiated highly active antiretroviral therapy. The seroprevalence of T. gondii infection was 10.2%, which did not differ with sex, age, route of transmission, birth inside or outside of Taiwan, or CD4+ lymphocyte stratifications. After a median observation duration of 603 days (range, 1–3264 days), 10 (1.2%) patients developed 11 episodes of TE after a median interval of 30 days (range, 1–941 days) between enrolment and diagnosis of TE, with an incidence of 0.59 per 100 person-years (PY) (95% confidence interval, 0.56–0.63 per 100 PY). We concluded that the incidence of TE of HIV-infected patients in Taiwan was lower than that reported in western countries because of a lower seroprevalence of T. gondii infection and use of antimicrobial prophylaxis and antiretroviral therapy, although most of the patients were at the late stage of HIV infection.