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Background Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings. Methods Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an RCT comparing the effects of early (within 14 days of CM) and late (14–56 days after CM) ART on all-cause mortality, adjusting for potential confounders. Results Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33–44) years; the median CD4+ T-cell count, 19/μL (10–56/μL); and median HIV viral load, 5.3 (4.9–5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval,.64–2.56) and 1.40 (.66–2.95), respectively. Conclusions We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non‐liver malignancies in people living with HIV (PLWH). Methods: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. Results: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person‐years of follow‐up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94–8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47–12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV‐positive versus HBV‐negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00–1.51]. Compared to HBV‐negative individuals, HBsAg‐positive/HBV‐DNA‐positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00–1.89) and NHL (aIRR 2.57; 95% CI 1.16–5.68). There was no significant association between HBV and lung or anal cancer. Conclusions: We found increased rates of nonliver malignancies in HBsAg‐positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV‐positive subjects with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Introduction: Since the beginning of the HIV epidemic in resource‐rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS‐defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV‐RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time‐updated CD4 counts, HIV‐RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV‐RNA was stratified as low (<400), medium (400 to 10,000) or high (>10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person‐years (py) in 10,476 patients. The PjP incidence in the different plasma HIV‐RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV‐RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. [ABSTRACT FROM AUTHOR]

The article offers information of the challenges in solid organ transplantation (SOT) in HIV-infected patients. Topics discussed include challenges of poor outcomes of combined kidney- liver transplantation (CKLT) and simultaneous kidney- pancreas transplantation (SKPT) in HIV-infected patients; information of antiretroviral therapy (ART) has made HIV for HIV-infected patients; and rapid evolution in SOT in HIV-infected patients which involve Living-donor liver transplantation (LDLT.).

Summary Liver transplantation is increasingly performed in selected HIV-infected patients in most developed countries, with excellent results reported in patients with liver diseases unrelated to HCV. In contrast, survival in HCV/HIV-coinfected liver recipients is poorer than in HCV-monoinfected patients, due to more aggressive recurrence of HCV and consequent graft loss and death. Results from American, French, and Spanish cohort studies showed a 5-year survival rate of only 50–55%. Therefore, it is debated whether liver transplantation should be offered to HCV/HIV-coinfected patients. Studies have shown that the variables more consistently associated with poor outcome are: (1) the use of old or HCV-positive donors, (2) dual liver-kidney transplantation, (3) recipients with very low body mass index and (4) less site experience. However, the most effective factor influencing transplantation outcome is the successful treatment of HCV recurrence with anti-HCV. Survival is 80% in patients whose HCV infection resolves. Unfortunately, the rates of sustained virological response with pegylated-interferon plus ribavirin in coinfected recipients are low, particularly for genotype 1 (only 10%). Here we present a non-systematic review of the literature based on our own experience in different liver transplant scenarios. This review covers selection criteria in HIV-infected patients, pre- and post-LT management, donor selection, anti-HCV treatment, drug interactions with antiretrovirals and anti-HCV direct antiviral agents, hepatocellular carcinoma, and liver retransplantation. Recommendations are rated. Finally, we explain how the introduction of new effective and more tolerable direct antiviral agents may improve significantly the outcome of HCV/HIV-coinfected liver recipients. [ABSTRACT FROM AUTHOR]

The author reflects on the prevalence of enterococci, which are the third most etiologic agent of infective endocarditis. The author states that enterococcal infections are relevant among the elderly and patients with comorbid conditions in the health-care setting. He mentions that about 90% cases of enterococcal endocarditis are caused by enterococcus faecalis. He also adds that the percentage of patients requiring cardiac surgery is 42% and the 1-year mortality rate is 29%.

Objectives: We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods: Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997-2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30-270 days after AIDS event) cART. Results: The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/μL and 5.2 (4.5, 5.7) log10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20). Conclusions: Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting. [ABSTRACT FROM AUTHOR]

The periannular extension of infection in prosthetic valve endocarditis (PVE) is a serious complication of infective endocarditis associated with high mortality. Periannular lesions in PVE occasionally rupture into adjacent cardiac chambers, leading to aortocavitary fistulae and intracardiac shunting. It is unknown whether the prognosis of patients with aortocavitary fistulae is worse than that of those with nonruptured abscesses. The aims of this study were to determine the distinctive clinical characteristics of patients with PVE and either aortocavitary fistulization or nonruptured abscesses. In a retrospective multicenter study of >872 PVE episodes, 150 patients (17%) with periannular complications in PVE in the aortic position were identified (29 with aortocavitary fistulization and 121 with nonruptured abscesses). Early-onset PVE was present in 73 patients (49%). Rates of heart failure (p = 0.09), ventricular septal defect (p <0.01), and third-degree atrioventricular block (p = 0.07) were higher in patients with fistulization. Surgical treatment was undertaken in 128 patients (83%). In-hospital mortality in the overall population was 39%. Multivariate analysis identified heart failure (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.6 to 6.8), renal failure (OR 2.5, 95% CI 1.2 to 5.2), and co-morbidity (OR 2.4, 95% CI 1.1 to 5.1) as independent risk factors for death. Fistulous tract formation was not associated with increased in-hospital mortality (OR 1.6, 95% CI 0.7 to 3.7). The actuarial 5-year survival rate in surgical survivors was 100% in patients with fistulae and 78% in patients with nonruptured abscesses (log-rank p = 0.14). In conclusion, aortocavitary fistulous tract formation in PVE complicated with periannular complications is associated with higher rates of heart failure, ventricular septal defect, and atrioventricular block than nonruptured abscesses. Despite the frequent complications, fistulous tract formation in the current era of infective endocarditis is not an independent risk factor for mortality. [Copyright &y& Elsevier]

The extension of infection in native valve infective endocarditis (IE) from valvular structures to the periannular tissue is incompletely understood. It is unknown, for example, whether the prognosis of patients with aortocavitary fistulae is worse than that of those with nonruptured abscesses. The aims of this study were to determine the distinct clinical characteristics of patients with aortocavitary fistulae and nonruptured abscesses in native valve IE and to evaluate the impact of fistulization on the outcomes of patients with native aortic valve IE complicated with periannular lesions. In a retrospective multicenter study of 2,055 native valve IE episodes, 201 patients (9.8%) with periannular complications in aortic valve IE were identified (46 with aortocavitary fistulization and 155 with nonruptured abscesses). Rates of heart failure (p = 0.07), ventricular septal defect (p <0.001), and third-degree atrioventricular block (p = 0.07) were higher in patients with fistulization. Surgical treatment was undertaken in 172 patients (86%), and in-hospital mortality in the overall population was 29%. Multivariate analysis identified age >60 years (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.3 to 5.2), renal failure (OR 3.0, 95% CI 1.5 to 6.0), and moderate or severe heart failure (OR 2.5, 95% CI 1.2 to 5.2) as independent risk factors for death. There was a trend toward increased in-hospital mortality in patients with aortocavitary fistulae (OR 1.5, 95% CI 0.7 to 3.0). The actuarial 5-year survival rate in surgical survivors was 80% in patients with fistulae and 92% in patients with nonruptured abscesses (log-rank p = 0.6). In conclusion, aortocavitary fistulous tract formation in the setting of native valve IE is associated with higher rates of heart failure, ventricular septal defect, and atrioventricular block than nonruptured abscess. Despite these higher rates of complications, fistulous tract formation in the current era of IE is not an independent risk factor for mortality. [Copyright &y& Elsevier]

The purpose of this investigation was to study the influence of diabetes mellitus (DM) on outcomes of infective endocarditis (IE). Outcomes were compared between 150 diabetic and 905 non-diabetic patients with IE from the International Collaboration on Endocarditis Merged Database. Compared to non-diabetic patients, diabetic patients were older (median age 63 vs 57 y, p [ABSTRACT FROM AUTHOR]

Background. To our knowledge, no randomized trials have evaluated whether prophylaxis against toxoplasmic encephalitis can be safely discontinued after the CD4+ T cell count increases in response to highly active antiretroviral therapy. Methods. We conducted a randomized, nonblinded, multicenter clinical trial of the discontinuation of primary or secondary prophylaxis against toxoplasmic encephalitis in human immunodeficiency virus (HIV)-infected patients with a sustained response to antiretroviral therapy (defined as a CD4+ T cell count of ⩾200 cells/mm3 and a plasma HIV type 1 [HIV-1] RNA level of <5000 copies/mL for at least 3 months). Prophylaxis was restarted if the CD4+ T cell count decreased to <200 cells/mm3. Results. The 381 patients receiving primary prophylaxis had a median CD4+ T cell count on study entry of 343 cells/mm3, and 318 (83%) of 381 patients had undetectable HIV-1 RNA in plasma. After a median followup period of 25 months (409 person-years), there were no episodes of toxoplasmic encephalitis among the 196 patients who discontinued prophylaxis (at 1 year, the upper limit of the 95% confidence interval for relapse rate was 2.40%). For the 57 patients receiving secondary prophylaxis, the median CD4+ T cell count on entry was 407 cells/mm3, and 49 (86%) of 57 patients had undetectable HIV-1 RNA in plasma. After a median follow-up period of 30.5 months (69 person-years), there were no episodes of toxoplasmic encephalitis among the 28 patients who discontinued prophylaxis (at 1 year, the upper limit of the 95% confidence interval for relapse rate was 16%). Conclusions. In HIV-infected adult patients receiving effective highly active antiretroviral therapy, primary and secondary prophylaxis against toxoplasmic encephalitis can be safely discontinued after the CD4+ T cell count has increased to ⩾200 cells/mm3 for >3 months. [ABSTRACT FROM AUTHOR]

The aims of this study were to determine the clinical characteristics and outcome of patients who had definite infective endocarditis (IE) complicated by aortic ring abscess formation that was detected with transesophageal echocardiography (TEE) and to determine the prognostic significance of abscess formation in aortic valve IE. Patients who had aortic valve IE were selected from the International Collaboration on Endocarditis Merged Database (ICE-MD) if they underwent TEE. Among 311 patients who had definite aortic valve IE, 67 (22%) had periannular abscesses. They were more likely to have infection in the setting of a prosthetic valve (40% vs 19%, p <0.001) and coagulase-negative staphylococcal IE (18% vs 6%, p < 0.01) and less likely to have streptococcal IE than were patients who did not develop abscess (28% vs 46%, p = 0.01). Systemic embolization, central nervous system events, and heart failure did not differ between those who developed abscess and those who did not, but power was limited. Patients who had abscess were more likely to undergo surgery (84% vs 36%, p <0.001), and their in-hospital mortality rate was higher (19% vs 11%, p = 0.09). Multivariate analysis of prognostic factors of mortality in aortic IE identified age (odds ratio [OR] 1.6, 95% confidence interval [CI]1.2 to 2.1), Staphylococcus aureus (S. aureus) infection (OR 2.4, 95% CI 1.1 to 5.2), and heart failure (OR 2.9, 95% CI 1.4 to 6.1) as variables that were independently associated with increased risk of death. Periannular abscess formation showed a nonsignificant trend toward an increased risk of death (OR 1.9, 95% CI 0.9 to 3.8). Multivariate analysis of prognostic factors of mortality in complicated aortic IE with abscess formation identified S. aureus infection (OR 6.9, 95% CI 1.6 to 29.4) as independently associated with increased risk of death. In conclusion, in the current era of TEE and high use of surgical treatment, periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. S. aureus infection is an independent prognostic factor for mortality in patients who have abscess formation. [Copyright &y& Elsevier]

Context The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown. Objectives To document the international emergence of health care–associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE. Design, Setting, and Participants Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003. Main Outcome Measure In-hospital mortality. Results S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care-associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons). Conclusions S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation. [ABSTRACT FROM AUTHOR]

Details a study which examined the effect of penicillin resistance of Streptococcus pneumoniae on the treatment of pneumococcal endocarditis (PE) in adults. Incidence of PE; Clinical presentation and complications of PE; Treatment of PE according to the antimicrobial susceptibility of isolates.

Introduction: HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). Methods: We included people living with HIV from 25 European cohorts 1983–2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. Results: We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3–10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193–540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300–103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02–3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5–2.2). Conclusions: Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important. [ABSTRACT FROM AUTHOR]

Presents the results of a study which examined the impact of human immunodeficiency virus (HIV) infection on the clinical characteristics and outcome of infective endocarditis (IE) in intravenous drug users. Methodology used in the study; Characteristics of IE in HIV-infected and non-HIV-infected intravenous drug users; Comparison of complications; What the findings of the study showed.

Evaluates the efficacy of sulfadiazine-pyrimethamine maintenance therapy administered twice weekly to prevent toxoplasmic encephalitis relapse in Spanish patients with AIDS. Study design and setting; Selection of patients; Clinical and biological evaluations; Follow-up.

During the past 6 decades, there have been numerous changes in prosthetic valve endocarditis (PVE), currently affecting an older population and increasing in incidence in patients with transcatheter-implanted valves. Significant microbiologic (molecular biology) and imaging diagnostic (fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography) advances have been incorporated into the 2023 Duke-International Society for Cardiovascular Infectious Diseases infective endocarditis diagnostic criteria, thus increasing the diagnostic sensitivity for PVE without sacrificing specificity in validation studies. PVE is a life-threatening disease requiring management by multidisciplinary endocarditis teams in cardiac centers to improve outcomes. Novel surgical options are now available, and an increasing set of patients may avoid surgical intervention despite indication. Selected patients may complete parenteral or oral antimicrobial treatment at home. Finally, patients with prosthetic valves implanted surgically or by the transcatheter approach are candidates for antibiotic prophylaxis before invasive dental procedures. [Display omitted] • PVE occurs in an increasingly aged population, including patients with transcatheter-implanted valves, and is associated with high mortality. • Recently revised diagnostic criteria for PVE incorporate advances in microbiology and molecular and imaging modalities. • Ongoing clinical studies are evaluating oral antimicrobial regimens to complete therapy at home and provide effective prophylaxis. [ABSTRACT FROM AUTHOR]

Background The 2023 Duke–International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required. Methods We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria. Results A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P <.001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P <.001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact. Conclusions The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE. [ABSTRACT FROM AUTHOR]

The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection. [ABSTRACT FROM AUTHOR]

Background While both the burden of therapy and the individual drugs in bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and dolutegravir/lamivudine differ, it is unclear whether their real-life tolerability may be also different. Methods Single-centre, clinical cohort analysis of all virologically suppressed persons with HIV (PWH) who were first prescribed bictegravir as BIC/TAF/FTC or dolutegravir as dolutegravir/lamivudine and had taken ≥1 dose of study medication. Major outcomes were discontinuations either for any reason or due to toxicity. Incidence was calculated as number of episodes per 100 person-years adjusted through propensity score analysis. Results Relative to persons treated with BIC/TAF/FTC (n  = 1231), persons treated with dolutegravir/lamivudine (n  = 821) were older and had more AIDS-defining conditions although better HIV control. After a median follow-up of 52 weeks, adjusted incidence rates for discontinuation were 6.68 (95% CI 5.18–8.19) and 8.44 (95% CI 6.29–10.60) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.26 (95% CI 0.89–1.78) relative to BIC/TAF/FTC (P  = 0.1847). Adjusted incidence rates for discontinuation due to toxicity were 3.88 (95% CI 2.70–5.06) and 4.62 (95% CI 3.05–6.19) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.19 (95% CI 0.75–1.90) relative to BIC/TAF/FTC (P  = 0. 4620). Adverse events leading to discontinuation were neuropsychiatric (n  = 42; 2%), followed by gastrointestinal (n  = 23; 1%), dermatological (n  = 15; 1%) and weight increase (n  = 15; 1%), without differences between regimens. Conclusions Switching to BIC/TAF/FTC or dolutegravir/lamivudine showed no difference in the risks of overall or toxicity-related discontinuations or in the profile of adverse events leading to discontinuation. [ABSTRACT FROM AUTHOR]

For infective endocarditis (IE) with extensive perivalvular lesions or end-stage cardiac failure, heart transplantation (HT) may be the last resort. We retrospectively collected all cases of HT for IE within the International Collaboration on Endocarditis (ICE) network. Between 1991 and 2021, 20 patients (5 women, 15 men), median age 50 years [interquartile range, 29–61], underwent HT for IE in Spain (n = 9), France (n = 6), Switzerland (n = 2), Colombia, Croatia, and USA (n = 1). IE affected prosthetic (n = 10), and native valves (n = 10), primarily aortic (n = 11) and mitral (n = 6). The main pathogens were oral streptococci (n = 8), Staphylococcus aureus (n = 5), and Enterococcus faecalis (n = 2). The major complications included heart failure (n = 18), peri-annular abscess (n = 10), and prosthetic valve dehiscence (n = 4). Eighteen patients had previous cardiac surgery for this episode of IE, and four were on circulatory support before HT (left ventricular assist-device and extra-corporeal membrane oxygenation, 2 patients each). The median time interval between first symptoms of IE and HT was 44.5 days [22–91.5]. The main post-HT complication was acute rejection (n = 6). Seven patients died (35%), four during the first month post-HT. Thirteen (81%) of the 16 patients discharged from the hospital survived with a median follow-up of 35.5 months [4–96.5] after HT, and no relapse of IE. IE is not an absolute contraindication for HT: Our case series and the literature review support that HT may be considered as a salvage treatment in highly-selected patients with intractable IE. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has exponentially increased during the last years. It is necessary to develop new antimicrobial drugs to prevent and treat infectious diseases caused by multidrug- or extensively-drug resistant (MDR/XDR)-bacteria. Host Defense Peptides (HDPs) have a versatile role, acting as antimicrobial peptides and regulators of several innate immunity functions. The results shown by previous studies using synthetic HDPs are only the tip of the iceberg, since the synergistic potential of HDPs and their production as recombinant proteins are fields practically unexplored. The present study aims to move a step forward through the development of a new generation of tailored antimicrobials, using a rational design of recombinant multidomain proteins based on HDPs. This strategy is based on a two-phase process, starting with the construction of the first generation molecules using single HDPs and further selecting those HDPs with higher bactericidal efficiencies to be combined in the second generation of broad-spectrum antimicrobials. As a proof of concept, we have designed three new antimicrobials, named D5L37βD3, D5L37D5L37 and D5LAL37βD3. After an in-depth exploration, we found D5L37D5L37 to be the most promising one, since it was equally effective against four relevant pathogens in healthcare-associated infections, such as methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis (MRSE) and MDR Pseudomonas aeruginosa, being MRSA, MRSE and P. aeruginosa MDR strains. The low MIC values and versatile activity against planktonic and biofilm forms reinforce the use of this platform to isolate and produce unlimited HDP combinations as new antimicrobial drugs by effective means. [ABSTRACT FROM AUTHOR]

A response by Jose M. Miro and colleagues to a letter to the editor about their article on the safety of discontinuing prophylaxis against Pneumocystis carinii pneumonia following an antiretroviral therapy in the January 18, 2005 issue of the "New England Journal of Medicine" is presented.

Background: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. Methods: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiretroviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and a plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. Results: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (388 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (65 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.57 episodes per 100 person-years). Conclusions: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months. (N Engl J Med 2001;344:159-67.) [ABSTRACT FROM AUTHOR]

The objective was to produce a cascade of care for Catalonia to gain a public health perspective on the overall quality of HIV services and allow comparison with other countries. It was constructed using the Integrated Epidemiological Surveillance System of HIV in Catalonia and data from the PISCIS Cohort. Estimates of the number of people living with HIV in Catalonia are modelled using Spectrum Projection Package 2011 (UNAIDS/WHO). Totals for each stage in the cascade are obtained by applying to the preceding stage a proportion estimated from available surveillance and cohort data. Undiagnosed HIV was estimated from the European literature. The proportions retained in care, on ART and virally suppressed were derived from the PISCIS cohort. Programmatic data on ART consumption was used to validate estimates. By the end of 2011 there were about 33,000 people living with HIV in Catalonia, 71% of which had been both diagnosed and linked to care. We estimate that 61% of all HIV infected persons were retained in care, 56% were on ART and 48% were virally suppressed. These figures data are comparable, although slightly lower, than that of France or the UK. The Cascade of HIV Care in Catalonia is similar to other western European countries such as France and the UK. Direct estimates of the undiagnosed HIV population and linkage to care are desirable but the contribution of cohort data to the cascade highlights their continued importance in HIV surveillance and design of evidence-based health strategies. [ABSTRACT FROM AUTHOR]

Background: Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting.Objectives: We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH).Methods: We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes.Results: After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78-1.04] or hospitalization (aOR 0.93; 95% CI, 0.60-1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or hospitalization (aOR 0.51; 95% CI, 0.15-1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10-1.07) compared with TAF/FTC.Conclusions: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management. [ABSTRACT FROM AUTHOR]

Background. Coagulase-negative staphylococci (CoNS) are an infrequent cause of native valve endocarditis (NVE), and our understanding of NVE caused by CoNS is incomplete. Method. The International Collaboration on Endocarditis-Prospective Cohort Study includes patients with endocarditis from 61 centers in 28 countries. Patients with definite cases of NVE caused by CoNS who were enrolled during the period June 2000-August 2006 were compared with patients with definite cases of NVE caused by Staphylococcus aureus and patients with NVE caused by viridans group streptococci. Multivariable logistic regression was used to determine factors associated with death in patients with NVE caused by CoNS. Results. Of 1635 patients with definite NVE and no history of injection drug use, 128 (7.8%) had NVE due to CoNS. Health care-associated infection occurred in 63 patients (49%) with NVE caused by CoNS. Comorbidities, long-term intravascular catheter use, and history of recent invasive procedures were similar among patients with NVE caused by CoNS and among patients with NVE caused by S. aureus. Surgical treatment for endocarditis occurred more frequently in patients with NVE due to CoNS (76 patients [60%]) than in patients with NVE due to S. aureus (150 [33%]; P<.01) or in patients with NVE due to viridans group streptococci (149 [44%]; P<.01). Despite the high rate of surgical procedures among patients with NVE due to CoNS, the mortality rates among patients with NVE due to CoNS and among patients with NVE due to S. aureus were similar (32 patients [25%] and 124 patients [27%], respectively; P = .44); the mortality rate among patients with NVE due to CoNS was higher than that among patients with NVE due to viridans group streptococci (24 [7.0%]; P<.01). Persistent bacteremia (odds ratio, 2.65; 95% confidence interval, 1.08-6.51), congestive heart failure (odds ratio, 3.35; 95% confidence interval, 1.57-7.12), and chronic illness (odds ratio, 2.86; 95% confidence interval, 1.34-6.06) were independently associated with death in patients with NVE due to CoNS (c index, 0.73). Conclusions. CoNS have emerged as an important cause of NVE in both community and health care settings. Despite high rates of surgical therapy, NVE caused by CoNS is associated with poor outcomes. [ABSTRACT FROM AUTHOR]

Infective endocarditis is a relatively rare, but deadly infection, with an overall mortality of around 20% in most series. Clinical manifestations have evolved in response to significant epidemiological shifts in industrialized nations, with a move toward a nosocomial or health-care-related pattern, in older patients, with more episodes associated with prostheses and/or intravascular electronic devices and a predominance of staphylococcal and enterococcal etiology.Diagnosis is often challenging and is based on the conjunction of clinical, microbiological, and imaging information, with notable progress in recent years in the accuracy of echocardiographic data, coupled with the recent emergence of other useful imaging techniques such as cardiac computed tomography (CT) and nuclear medicine tools, particularly 18F-fluorodeoxyglucose positron emission/CT.The choice of an appropriate treatment for each specific case is complex, both in terms of the selection of the appropriate agent and doses and durations of therapy as well as the possibility of using combined bactericidal antibiotic regimens in the initial phase and finalizing treatment at home in patients with good evolution with outpatient oral or parenteral antimicrobial therapies programs. A relevant proportion of patients will also require valve surgery during the active phase of treatment, the timing of which is extremely difficult to define. For all the above, the management of infective endocarditis requires a close collaboration of multidisciplinary endocarditis teams. [ABSTRACT FROM AUTHOR]

Longitudinal studies in HIV-1-infected individuals have indicated that 2 to 3 years of infection are required to develop broadly neutralizing antibodies. However, we have previously identified individuals with broadly neutralizing activity (bNA) in early HIV-1 infection, indicating that a vaccine may be capable of bNA induction after short periods of antigen exposure. Here, we describe 5 HIV-1 envelope sequences from individuals who have developed bNA within the first 100 days of infection (early neutralizers) and selected two of them to design immunogens based on HIV-1-Gag virus-like particles (VLPs). These VLPs were homogeneous and incorporated the corresponding envelopes (7 to 9 mg of gp120 in 1010 VLPs). Both envelopes (Envs) bound to well-characterized broadly neutralizing antibodies (bNAbs), including trimer-specific antibodies (PGT145, VRC01, and 35022). For immunogenicity testing, we immunized rabbits with the Env-VLPs or with the corresponding stabilized soluble envelope trimers. A short immunization protocol (105 days) was used to recapitulate the early nAb induction observed after HIV-1 infection in these two individuals. All VLP and trimeric envelope immunogens induced a comparably strong anti-gp120 response despite having immunized rabbits with 30 times less gp120 in the case of the Env-VLPs. In addition, animals immunized with VLP-formulated Envs induced antibodies that cross-recognized the corresponding soluble stabilized trimer and vice versa, even though no neutralizing activity was observed. Nevertheless, our data may provide a new platform of immunogens, based on HIV-1 envelopes from patients with early broadly neutralizing responses, with the potential to generate protective immune responses using vaccination protocols similar to those used in classical preventive vaccines. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess the clinical characteristics associated with the use of two-drug regimens (2DRs) and the factors associated with specific antiretrovirals in 2DRs in a large single-centre HIV cohort.Methods: Retrospective analysis of demographics, HIV characteristics and AIDS events, antiretroviral prescription, virological failure and genotypic resistance testing, and laboratory results from all adult people with HIV (PWH) prospectively followed at the Hospital Clinic of Barcelona who were receiving a 3DR or a 2DR in January 2020. We assessed factors associated with the probability of receiving 2DRs relative to three-drug regimens (3DRs) using a logistic regression model, controlling for age, sex and year of HIV diagnosis. The same methodology was applied to identify factors associated with the prescription of integrase inhibitor-based regimens or PI-based regimens among PWH receiving 2DRs.Results: There were 3432 (88%) PWH receiving 3DRs and 463 (12%) receiving 2DRs. In the final adjusted model, ≥2 previous virological failures, previous resistance mutations, previous AIDS diagnosis, longer time on current regimen, higher total cholesterol or triglycerides and lower baseline haemoglobin were independent factors associated with 2DRs. The majority of 2DRs included an integrase inhibitor or/and a PI. We identified independent factors associated with the inclusion of integrase inhibitors (lower HDL cholesterol) or PIs (prior AIDS, prior genotypic resistance mutations and lower CD4/CD8 ratio) in the 2DR.Conclusions: In this large single-centre HIV cohort, a worse cardiometabolic status or more archived resistance were key factors associated with inclusion of integrase inhibitors or PIs, respectively, in 2DRs. [ABSTRACT FROM AUTHOR]

Background Using data from the COHERE collaboration, we investigated whether primary prophylaxis for pneumocystis pneumonia (PcP) might be withheld in all patients on antiretroviral therapy (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count. Methods We implemented an established causal inference approach whereby observational data are used to emulate a randomized trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤200 cells/µL in line with existing recommendations. We compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/µL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio (HR) to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring. Results A total of 4813 patients (10 324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR,.8; 95% confidence interval,.6–1.1; P  = .2). Conclusions This study suggests that primary PcP prophylaxis might be safely withheld in confirmed virologically suppressed patients on ART, regardless of their CD4 count. [ABSTRACT FROM AUTHOR]

Background A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH. Methods PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations. Results We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296–552)/mm3, 936 (670–1304)/mm3, and 0.43 (0.28–0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2–37) and 18 (7–42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23–3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58–6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60–6.56] for KS; HR = 5.28 [95% CI = 2.17–12.83] for NHL). Conclusions Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3. [ABSTRACT FROM AUTHOR]

Background Little is known about the characteristics and impact of septic shock (SS) on the outcomes of infective endocarditis (IE). We aimed to investigate the characteristics and outcomes of patients with IE presenting with SS and to compare them to those of IE patients with sepsis (Se) and those with neither Se nor SS (no-Se-SS). Methods This is a prospective cohort study of 4864 IE patients from 35 Spanish centers (2008 to 2018). Logistic regression analyses were performed to identify risk factors for SS and mortality. Results Septic shock and Se presented in 597 (12.3%) and 559 (11.5%) patients, respectively. Patients with SS were younger and presented significantly higher rates of diabetes, chronic renal and liver disease, transplantation, nosocomial acquisition, Staphylococcus aureus , IE complications, and in-hospital mortality (62.5%, 37.7% for Se and 18.2% for no-Se-SS, P  < .001). Staphylococcus aureus (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.34–2.81; P  < .001), Gram negative (OR, 2.21; 95% CI, 1.25–3.91; P =.006), nosocomial acquisition (OR, 1.44; 95% CI, 1.07–1.94; P =.015), persistent bacteremia (OR, 1.82; 95% CI, 1.24–2.68; P =.002), acute renal failure (OR, 3.02; 95% CI, 2.28–4.01; P  < .001), central nervous system emboli (OR, 1.48; 95% CI, 1.08–2.01; P =.013), and larger vegetation size (OR, 1.01; 95% CI, 1.00–1.02; P. = 020) were associated with a higher risk of developing SS. Charlson score, heart failure, persistent bacteremia, acute renal failure, mechanical ventilation, worsening of liver disease, S aureus , and receiving aminoglycosides within the first 24 hours were associated with higher in-hospital mortality, whereas male sex, native valve IE, and cardiac surgery were associated with lower mortality. Conclusions Septic shock is frequent and entails dismal prognosis. Early identification of patients at risk of developing SS and early assessment for cardiac surgery appear as key factors to improve outcomes. [ABSTRACT FROM AUTHOR]

Background: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. Methods and Results: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. Conclusions: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations. [ABSTRACT FROM AUTHOR]

Candida infective endocarditis (IE) is increasingly common, yet most reports have been single-center reviews. We evaluated 16 patients with Candida IE nested within a cohort of 2,022 patients with IE. Prosthetic valve IE was more common in patients with Candida (50% vs 17%); mortality was 37% for patients with Candida. [ABSTRACT FROM AUTHOR]

Background: Enterococcal cardiovascular implantable electronic device (CIED) infections are not well characterized. Methods: Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective study of CIED infections, were used for descriptive analysis of adults with enterococcal CIED infections. Results: Of 433 patients, 21 (4.8%) had enterococcal CIED infection. Median age was 71 years. Twelve patients (57%) had permanent pacemakers, five (24%) implantable cardioverter defibrillators, and four (19%) biventricular devices. Median time from last procedure to infection was 570 days. CIED‐related bloodstream infections occurred in three patients (14%) and 18 (86%) had infective endocarditis (IE), 14 (78%) of which were definite by the modified Duke criteria. IE cases were classified as follows: valvular IE, four; lead IE, eight; both valve and lead IE, six. Vegetations were demonstrated by transesophageal echocardiography in 17 patients (81%). Blood cultures were positive in 19/19 patients with confirmed results. The most common antimicrobial regimen was penicillin plus an aminoglycoside (33%). Antibiotics were given for a median of 43 days. Only 14 patients (67%) underwent device removal. There was one death during the index hospitalization with four additional deaths within 6 months (overall mortality 24%). There were no relapses. Conclusions: Enterococci caused 4.8% of CIED infections in our cohort. Based on the late onset after device placement or manipulation, most infections were likely hematogenous in origin. IE was the most common infection syndrome. Only 67% of patients underwent device removal. At 6 months follow‐up, no CIED infection relapses had occurred, but overall mortality was 24%. [ABSTRACT FROM AUTHOR]

• Preliminary survey results and in-person presentations highlighted heterogeneity in dalbavancin use, confirming the need for expert guidance. • Experts suggest that a total dose of 3000 mg dalbavancin in 4 weeks covers treatment for 4–6 weeks. • Flexibility in dosing schedule is possible, depending on the healthcare setting. • Therapeutic drug monitoring should be used to guide the administration of a dose beyond 3000 mg and start between Day 28 and Day 35 where > 6 weeks of dalbavancin treatment duration is expected. Dalbavancin is a lipoglycopeptide with a long elimination half-life and is currently licensed for the treatment of acute bacterial skin and skin structure infections in adults. Dalbavancin's potential in treating off-label complex Gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking. This study aimed to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require > 2 weeks of treatment. A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin, which highlighted the heterogeneity in the regimens that were used. After review of the survey data and recent literature, this study presents expert panel proposals that accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to or exceeding 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3000 mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring > 2 weeks of treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in cases of renal failure. Specific dosing recommendations for other special populations require further investigation. These proposals based on expert opinion have been defined to encourage best practice with dalbavancin, to optimise its administration beyond the current approved licenced dose across different healthcare settings. [ABSTRACT FROM AUTHOR]

Abstract Background Pericardial effusion is a frequent finding in the setting of infective endocarditis. Limited data exists on clinical characteristics and outcomes in this group of patients. We aimed to determine the associated factors, clinical characteristics, and outcomes of patients who had pericardial effusion and native valve infective endocarditis. Methods and results A total of 1205 episodes of infective endocarditis from 25 Spanish centers between June 2007 and March 2013 within the Spanish Collaboration on Endocarditis (GAMES) registry were included. Echocardiogram at admission, clinical and microbiological variables, and one-year follow-up were analyzed. Pericardial effusion was observed in 7.8% (94/1205 episodes) of episodes of infective endocarditis, most of them being mild or moderate (93.6%). The presence of pericardial effusion was associated with a higher risk of heart failure during admission (OR 1.9; CI 95% 1.2–3.0). Patients with pericardial effusion had a higher rate of surgery (53.2% vs. 41.1%; p = 0.02); however, this association was no longer significant after adjusting for possible confounders (OR 1.4; CI 95% 0.9–2.2; p = 0.10). The presence of pericardial effusion was not associated with a higher in-hospital or one-year mortality (33.0% vs. 25.2%; p = 0.10 and 40.2% vs. 37.3%; p = 0.60 respectively). Conclusions The prevalence of pericardial effusion in patients with infective endocarditis was lower than previously reported. The presence of pericardial effusion is associated with the development of heart failure during hospitalization making it a warning sign, possibly reflecting indirectly a mechanical complication, which, however, if treated surgically in a timely manner does not change the final outcome of patients. Highlights • The prevalence of pericardial effusion in patients with infective endocarditis was lower than previously reported. • The presence of pericardial effusion is associated with the development of heart failure during hospitalization. • Pericardial effusion was not associated with a worse clinical outcome. [ABSTRACT FROM AUTHOR]

Among the viridans group streptococci, S. mitis-oralis strains are frequently resistant to multiple β-lactams and tolerant to vancomycin (VAN). This scenario has led to the proposed clinical use of newer agents, like daptomycin (DAP) for such S. mitis-oralis strains. However, recent recognition of the rapid and durable emergence of high-level DAP-resistance (DAP-R; DAP MICs > 256 µg/ml) induced by DAP exposures in vitro and in vivo has dampened enthusiasm for such approaches. In this study, we evaluated a broad range of DAP combination regimens in vitro for their capacity to prevent emergence of high-level DAP-R in a prototype S. mitis-oralis strain (351) during serial passage experiments, including DAP + either gentamicin (GEN), rifampin (RIF), trimethoprim-sulfamethoxazole (TMP-SMX), imipenem (IMP), ceftaroline (CPT), tedizolid (TDZ), or linezolid (LDZ). In addition, we assessed selected DAP combination regimens for their ability to exert either an early bactericidal impact and/or synergistically kill the S. mitis-oralis study strain. During serial passage, three of the eight antibiotic combinations (DAP + GEN, CPT, or TMP- SMX) exhibited significantly reduced DAP MICs (≈ by 8-40 fold) vs serial exposure in DAP alone (DAP MICs > 256 µg/ml). In addition, combinations of DAP + GEN and DAP + CPT were both bactericidal and synergistic in early time-kill curve interactions. [ABSTRACT FROM AUTHOR]

Background: There is little information concerning infective endocarditis (IE) in patients with bicuspid aortic valve (BAV) or mitral valve prolapse (MVP). Currently, IE antibiotic prophylaxis (IEAP) is not recommended for these conditions.Objectives: This study sought to describe the clinical and microbiological features of IE in patients with BAV and MVP and compare them with those of IE patients with and without IEAP indication, to determine the potential benefit of IEAP in these conditions.Methods: This analysis involved 3,208 consecutive IE patients prospectively included in the GAMES (Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España) registry at 31 Spanish hospitals. Patients were classified as high-risk IE with IEAP indication (high-risk group; n = 1,226), low- and moderate-risk IE without IEAP indication (low/moderate-risk group; n = 1,839), and IE with BAV (n = 54) or MVP (n = 89).Results: BAV and MVP patients had a higher incidence of viridans group streptococci IE than did high-risk group and low/moderate-risk group patients (35.2% and 39.3% vs. 12.1% and 15.0%, respectively; all p < 0.01). A similar pattern was seen for IE from suspected odontologic origin (14.8% and 18.0% vs. 5.8% and 6.0%; all p < 0.01). BAV and MVP patients had more intracardiac complications than did low/moderate-risk group (50% and 47.2% vs. 30.6%, both p < 0.01) patients and were similar to high-risk group patients.Conclusions: IE in patients with BAV and MVP have higher rates of viridans group streptococci IE and IE from suspected odontologic origin than in other IE patients, with a clinical profile similar to that of high-risk IE patients. Our findings suggest that BAV and MVP should be classified as high-risk IE conditions and the case for IEAP should be reconsidered. [ABSTRACT FROM AUTHOR]

INTRODUCTION: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. METHODS: We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. RESULTS: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). CONCLUSIONS: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival. [ABSTRACT FROM AUTHOR]

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. [ABSTRACT FROM AUTHOR]

Treatment completion is essential for the effectiveness of any latent tuberculosis infection (LTBI) regimen. The Tuberculosis Trials Consortium (TBTC) Study 33 (iAdhere) combined self-report and pill counts – standard of care (SOC) with a medication event monitoring system (MEMS) to determine treatment completion for 12-dose once-weekly isoniazid and rifapentine (3HP). Understanding the performance of SOC relative to MEMS can inform providers and suggest when interventions may be applied to optimize LTBI treatment completion. iAdhere randomized participants to directly observed therapy (DOT), SAT, or SAT with text reminders in Hong Kong, South Africa, Spain and the United States (U.S.). This post-hoc secondary analysis evaluated treatment completion in both SAT arms, and compared completion based on SOC with MEMS to completion based on SOC only. Treatment completion proportions were compared. Characteristics associated with discordance between SOC and SOC with MEMS were identified. Overall 80.8% of 665 participants completed treatment per SOC, compared to 74.7% per SOC with MEMS, a difference of 6.1% (95%CI: 4.2%, 7.8%). Among U.S. participants only, this difference was 3.3% (95% CI: 1.8%, 4.9%). Differences in completion was 3.1% (95% CI: −1.1%, 7.3%) in Spain, and 36.8% (95% CI: 24.3%, 49.4%) in South Africa. There was no difference in Hong Kong. When used for monitoring 3HP, SOC significantly overestimated treatment completion in U.S. and South Africa. However, SOC still provides a reasonable estimate of treatment completion of the 3HP regimen, in U.S., Spain, and Hong Kong. • Pill count with self-report overstates treatment completion compared to MEMS. • Reasonable estimate provided by pill count with self-report in most settings. • Interventions may help current smokers or household clusters in absence of MEMS. [ABSTRACT FROM AUTHOR]

Background: Total CD4+ T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals. Methods: CD4+ count and CD4/CD8 ratio were analyzed using data from 2 cohorts: SPARTAC trial and the UK HIV Seroconverters Cohort where primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models, we examined the effect of CD4/ CD8 ratio at seroconversion on disease progression (CD4 ,350 cells per cubic millimeter/ART initiation) and factors associated with time from ART initiation to CD4/CD8 normalization (ratio .1.0). Findings: Of 573 seroconverters, 482 (84%) had abnormal CD4/ CD8 ratios at HIV seroconversion. Individuals with higher CD4/ CD8 ratio at seroconversion were significantly less likely to reach the disease progression endpoint [adjusted hazard ratio (aHR) (95% CI) < 0.52 (0.32 to 0.82), P < 0.005]. The longer the interval between seroconversion and ART initiation [HR (95% CI) < 0.98 per month increase (0.97, 0.99), P , 0.001], the less likely the CD4/ CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) = 2.47 (1.67 to 3.67), P , 0.001] than those initiating later. Interpretation: Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio. [ABSTRACT FROM AUTHOR]