35 research outputs found
Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan
<div><p>Objectives</p><p>Two nucleos(<i>t</i>)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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div
Univariate analyses for factors associated with skin rash after initiation of nNRTI-containing regimens within the first 4 weeks.
<p>Univariate analyses for factors associated with skin rash after initiation of nNRTI-containing regimens within the first 4 weeks.</p
Multivariate analyses for factors associated with hepatotoxicity after initiation of nNRTI-containing regimens within the first 4 weeks (HBV/HIV co-infected vs HIV mono-infected).
<p>Multivariate analyses for factors associated with hepatotoxicity after initiation of nNRTI-containing regimens within the first 4 weeks (HBV/HIV co-infected vs HIV mono-infected).</p
Multivariate analyses for factors associated with skin rash after initiation of nNRTI-containing regimens within the first 4 weeks (patients receiving rilpivirine were excluded).
<p>Multivariate analyses for factors associated with skin rash after initiation of nNRTI-containing regimens within the first 4 weeks (patients receiving rilpivirine were excluded).</p
Univariate analyses for factors associated with hepatotoxicity after initiation of nNRTI-containing regimens within the first 4 weeks.
<p>Univariate analyses for factors associated with hepatotoxicity after initiation of nNRTI-containing regimens within the first 4 weeks.</p
Multicenter Study of Trimethoprim/Sulfamethoxazole-Related Hepatotoxicity: Incidence and Associated Factors among HIV-Infected Patients Treated for <i>Pneumocystis jirovecii</i> Pneumonia
<div><p>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 <i>Pneumocystis jirovecii</i> pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of <i>P. jirovecii</i> 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. <i>NAT1</i> and <i>NAT2</i> 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, <i>NAT1</i> and <i>NAT2</i> 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.</p></div
Multivariate logistic regression for the factors associated with trimethoprim/sulfamethoxazole-related hepatotoxicity.
<p><b>Note:</b> Data represents the point estimate of the odds ratio for developing hepatotoxicity with 95% confidence interval.</p><p><b>Abbreviations:</b> BMI, body-mass index (kg/m<sup>2</sup>); TMP/SMX, trimethoprim/sulfamethoxazole.</p><p>Multivariate logistic regression for the factors associated with trimethoprim/sulfamethoxazole-related hepatotoxicity.</p
Clinical characteristics of HIV-infected patients with and those without hepatotoxicity after receiving trimethoprim/sulfamethoxazole for treatment of <i>Pneumocystis jirovecii</i> pneumonia.
<p><b>Note:</b> Data represent the median value (range) for continuous variables and the number of cases (%) for categorical variables. N indicates the number of patients being tested.</p><p><b>Abbreviations:</b> AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; BMI, body-mass index; HBsAg, hepatitis B virus surface antigen; HCV, hepatitis C virus; IDU, injecting drug user; LDH, lactate dehydrogenase; TMP/SMX, trimethoprim/sulfamethoxazole; <i>NAT1</i>, <i>N</i>-acetyltransferase-1; <i>NAT2</i>, <i>N</i>-acetyltransferase-2.</p><p>Clinical characteristics of HIV-infected patients with and those without hepatotoxicity after receiving trimethoprim/sulfamethoxazole for treatment of <i>Pneumocystis jirovecii</i> pneumonia.</p
Risk factors associated with the development of seizures among adult patients treated with ertapenem: A matched case-control study
<div><p>Objective</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div
Trends of incidence of trimethoprim/sulfamethoxazole-related hepatotoxicity (Y-axis) and daily dose of fluconazole in mg/kg (X-axis) (<i>P</i> for trends, 0.343).
<p>Trends of incidence of trimethoprim/sulfamethoxazole-related hepatotoxicity (Y-axis) and daily dose of fluconazole in mg/kg (X-axis) (<i>P</i> for trends, 0.343).</p