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Background: The indications for lumbar puncture in non-HIV-infected, non-transplant (NHNT) patients with cryptococcosis without meningeal signs need to be more fully defined. Objectives: This study was designed to determine the optimal predictors of central nervous system (CNS) involvement in adult NHNT patients with cryptococcosis. Methods: The study population consisted of adult NHNT patients with culture-confirmed cryptococcosis who sought care at a university hospital in Taiwan from 2002 to 2016. We used a case-control method to identify the clinical characteristics and laboratory findings associated with CNS involvement in patients who underwent a diagnostic lumbar puncture. In the sensitivity analysis, we included additional control patients who did not undergo lumbar puncture, but were followed beyond 12 months without the development of CNS involvement in the absence of exposure to any fungicidal agents. Results: We entered 270 NHNT adult patients into the study during the 15-year period. CNS involvement was confirmed in 66 (71.0%) of 93 patients who underwent lumbar puncture. A multivariable analysis revealed that presence of neurological manifestations and elevated serum CRAG titers were independently associated with a 23.97-fold (95% confidence interval [CI], 4.37–182.23) and 1.53-fold (per 2-fold increment, 95% CI 1.26–1.92) increased odds ratio for CNS involvement, respectively. Headache and focal neurologic signs were independently associated with CNS involvement. A cut-off serum CRAG titer of ≥1:64 provided the highest diagnostic performance by Youden index (sensitivity 83% and specificity 65%). Similar findings were noted in the sensitivity analysis including 198 (73%) patients. Conclusion: Lumbar puncture is indicated for NHNT patients with cryptococcosis who have neurologic manifestations or a serum CRAG titer of ≥1:64. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to describe the evolution of the seroprevalence of hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-positive patients included in two cohorts in Taiwan. Methods: We retrospectively collected the information on demographic and clinical characteristics of 4,025 and 3,856 HIV-positive Taiwanese, who were aged 18 years or older at designated hospitals around Taiwan in 2004–2007, when an outbreak of HIV infection was occurring, and 2012–2016, when the outbreak was controlled with the implementation of harm reduction program, respectively. Comparisons of HCV seropositivity were made among different age and risk groups for HIV transmission between these two cohorts. Results: The overall HCV seroprevalence of the 2004–2007 cohort and 2012–2016 cohort was 43.4% (1,288/2,974) and 18.6% (707/3,793), respectively (P<0.001). The HCV seroprevalence among injecting drug users (IDUs), though decreasing, was constantly high across the two cohorts, 96.4% and 94.0% (P = 0.02), respectively, and all age groups. In contrast, the corresponding figures among men who have sex with men (MSM) and heterosexuals in the two cohorts were 5.9% vs. 3.5% (P = 0.002) and 9.4% vs. 10.9% (P = 0.59), respectively. Among sexually transmitted HIV-positive patients, HCV seropositivity was significantly correlated with age (adjusted odds ratio [aOR], per 1-year increase, 1.03; 95% confidence interval [CI], 1.02–1.05) and a rapid plasma reagin (RPR) titer ≥1:8 (aOR, 1.58; 95% CI, 1.03–2.43) in a multivariate analysis including age, gender, route for HIV transmission, baseline CD4 count and plasma HIV RNA load, the presence of hepatitis B surface antigen, and an RPR titer ≥1:8. Compared with heterosexuals, the aOR for HCV seropositivity among MSM was 0.47 (95% CI, 0.31–0.72). Conclusions: HCV seroprevalence among HIV-positive patients in Taiwan decreased with time, probably related to the inclusion of younger adults and more non-IDUs, and remained high among IDUs. HCV seropositivity was associated with age and an RPR titer ≥1:8 among patients who acquired HIV through sexual contact. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to describe the seroprevalence of hepatitis A virus (HAV) in HIV-positive adult patients in Taiwan between 2012 and 2016 and to examine the evolution of HAV seroprevalence between 2004–2007 and 2012–2016. Methods: Clinical information and data of anti-HAV antibody results were collected from 2,860 antiretroviral-naïve HIV-positive Taiwanese aged 18 years or older who initiated combination antiretroviral therapy at 11 hospitals around Taiwan between 2012 and 2016 (2012–2016 cohort). A multivariate logistic regression model was applied to identify independent variables associated with HAV seropositivity. Comparisons of HAV seroprevalences and associated clinical characteristics were made between this 2012–2016 cohort and a previous cohort of 1580 HIV-positive patients in 2004–2007 (2004–2007 cohort). Results: Of the 2,860 HIV-positive patients between 2012 and 2016, the overall HAV seropositivity rate was 21.2% (605/2860), which was independently associated with an older age (adjusted odds ratio [AOR], per 1-year increase, 1.13; 95% confidence interval [95% CI], 1.11–1.15) and co-infection with hepatitis B virus (AOR 1.44; 95% CI, 1.08–1.93). Residence in southern Taiwan (AOR 0.49; 95% CI, 0.34–0.72) was inversely associated with HAV seropositivity. The overall HAV seroprevalence in the 2012–2016 cohort was significantly lower than that in the 2004–2007 cohort (21.2% vs 60.9%, p<0.01). The decreases of HAV seropositivity rate were observed in nearly every age-matched group, which suggested the cohort effect on HAV seroepidemiology. However, among individuals aged 25 years or younger, the HAV seropositivity rate increased from 3.8% (2/52) in the 2004–2007 cohort to 8.5% (50/587) in the 2012–2016 cohort, with 95.4% (560/587) being MSM in this age group of the latter cohort. Conclusions: HAV seroprevalence has decreased with time among HIV-positive adults in Taiwan. The cohort effect has increased the number of young HIV-positive patients that are susceptible to HAV infection in a country without nationwide childhood vaccination program against HAV. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to compare the characteristics of those ertapenem-treated adult patients with and without development of seizures, and identify the associated factors for the development of seizures. Methods: This retrospective study was conducted at Chia-Yi Christian Hospital from January 2012 to December 2014. Patients developing seizures during their ertapenem treatment course were identified as case patients. Those without seizures who had received ertapenem for at least five days were considered as the pool of control patients. For each case patient, four matched patients from the control pool were randomly selected as the final control group, based on age, gender, and the date of ertapenem prescription. Results: A total of 1706 ertapenem-treated patients were identified, 33 (1.9%) individuals developed seizures with the enrollment of 132 matched control patients. Among these 33 patients, the average age was 79.3 ± 7.5 years, and 20 (60.6%) were male. The mean Charlson co-morbidity score was 4.5 ± 2.4, and the first episode of seizure happened 3.3 ± 2.6 days after receiving ertapenem. In multivariate logistic regression analysis, the independent predictors associated with the development of ertapenem-associated seizures were old stroke (OR, 14.36; 95% CI, 4.38–47.02; p < 0.0001), undergoing brain images within one year prior to the admission (OR, 5.73; 95% CI, 1.78–18.43; p = 0.0034), low hemoglobin level (OR, 3.88; 95% CI, 1.28–12.75; p = 0.0165) and low platelet count (OR, 4,94; 95% CI, 1.56–15.68; p = 0.0067) at presentations, and protective factors against the development of seizures were heart failure (OR, 0.04; 95% CI, 0.00–0.63; p = 0.0222), concomitant use of steroids (OR, 0.19; 95% CI, 0.05–0.77; p = 0.0201), or antiplatelet agents (OR, 0.12; 95% CI, 0.02–0.63, p = 0.0123) with ertapenem. Conclusions: The development of ertapenem-associated seizures may occur more frequently and much earlier due to its widespread use in treating drug-resistant pathogens, especially when these pathogens emerged worldwide.Our study would help physician to estimate the risk of developing seizure among patients receiving ertapenem. [ABSTRACT FROM AUTHOR]

Objectives: The international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of late cART initiation in Taiwan. Methods: Between June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm3 or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART. Results: We included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm3 in 2012 to 298 cells/mm3 in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 (P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio [AOR], 1.05; 95% CI, 1.04–1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04–1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33–2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04–2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio [AHR], 5.40; 95% CI, 2.14–13.65) and older age (AHR, 1.06; 95% CI, 1.03–1.10). Conclusions: While the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population. [ABSTRACT FROM AUTHOR]

Objectives: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. Methods: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. Results: During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031–1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816–3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439–5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150–4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051–7.521) were independently associated with the development of hepatotoxicity. Conclusions: The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens. [ABSTRACT FROM AUTHOR]

The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145–0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity. [ABSTRACT FROM AUTHOR]