Prevalence of invasive fungal disease in hematological patients at a tertiary university hospital in Singapore

<p>Abstract</p> <p>Background</p> <p>The use of newer azoles as prophylaxis in hematological patients undergoing stem cell transplantation or immunosuppressive chemotherapy has been shown to decrease the risk of developing invasive fungal disease (IFD). However, the cost-effectiveness of such a strategy is dependent on the local epidemiology of IFD. We conducted an audit of hematological patients with IFD in our institution in order to derive the prevalence and types of IFD that occur locally.</p> <p>Findings</p> <p>We conducted a retrospective chart review of all hematological patients who developed possible, probable or definite IFD according to EORTC/MSG criteria in the period from Oct 2007 to Apr 2010. The prevalence of IFD was determined via correlation with institutional database records of all hematological patients treated at our institution over the same time period.</p> <p>There were 39 cases of IFD diagnosed during the study period, with 8 (20.5%) possible, 19 (48.7%) probable and 12 (30.8%) definite cases of IFD. <it>Aspergillus </it>spp. accounted for 83.9% of all probable and definite infections. There was 1 case each of <it>Rhinocladelia </it>spp., <it>Coprinopsis cinerea</it>, <it>Exserohilum </it>spp. sinusitis and <it>Rhizopus </it>spp. sinusitis. IFD occurred in 12 of 124 (9.7%) AML and 4 of 103 (3.9%) ALL patients treated at our institution respectively. There were 10 (16.1%) infections among 62 allogeneic HSCT recipients, six of whom were having concurrent graft-versus-host disease (GVHD). Five other cases occurred after allogeneic HSCT failure, following salvage chemotherapy for disease relapse. The prevalence of IFD during induction chemotherapy was 8.9% (11 of 124 cases) for AML and 1.0% (1 of 103 cases) for ALL. Fluconazole prophylaxis had been provided for 28 out of the 39 (71.8%) cases, while 4 (10.3%) were on itraconazole prophylaxis. The in-hospital mortality was 28.2% (11 of 39 cases), of which 5 (12.8%) deaths were attributed to IFD.</p> <p>Conclusions</p> <p>The burden of IFD is high in our institution, especially in allogeneic HSCT recipients and patients on induction chemotherapy for AML. A prophylactic strategy directed against invasive mould infections for local high-risk patients may be considered as the comparative costs of treatment, prolonged hospitalisation and subsequent delayed chemotherapy favours such an approach.</p

Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium

Objectives: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. Methods: Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL. Results: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67–0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97–1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71–0.91], p<0.001) and PI/b (0.87 [CI 0.76–0.99], p = 0.04). Conclusion: In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes

Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium

BACKGROUND: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. METHODS: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. RESULTS: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively). INTERPRETATION: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences