Clinical Infectious Diseases最新文献

Endocarditis from melioidosis is rarely reported; only 14 cases have been reported in the literature. We present a fatal case of native aortic valve endocarditis due to Burkholderia pseudomallei complicated by embolic stroke and subdural empyema that occurred in a traveler who returned from Thailand to the United States.

A remote, motivational interviewing-informed intervention using self-administered point-of-care urine tenofovir testing improved long-term pre-exposure prophylaxis (PrEP) adherence among young U.S. men-who-have-sex-with-men in a pilot randomized trial. Participants increased hair tenofovir levels by one to two tablets weekly, with high feasibility and acceptability, supporting further implementation.

Background: The effect of archived lamivudine resistance mutations in the efficacy of dolutegravir plus lamivudine (DTG/3TC) remains unclear. We evaluated whether proviral-DNA M184V/I detection is associated with virological outcomes in the VOLVER-GESIDA 11820 study.

Methods: This open-label, single-arm, multicentre phase IIa trial (NCT04880785) enrolled virologically suppressed adults with documented or suspected historical lamivudine resistance if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Participants switched to DTG/3TC and were followed through week 96. Proviral-DNA M184V/I was assessed retrospectively by next-generation sequencing (NGS) of peripheral blood mononuclear cells at baseline and week 96.

Results: Of 121 participants, 94% had documented historical M184V/I. Proviral-DNA NGS detected M184V/I at ≥5% frequency in 37 (30.6%; 32 M184V, 5 M184I) at baseline and/or week 96: 12 only at baseline, 13 only at week 96, and 12 at both timepoints. Two virological failures occurred within the first 48 weeks; none were observed thereafter. No treatment-emergent resistance was detected. In the ITT-e population (Snapshot analysis), HIV-1 RNA <50 copies/mL at week 96 was maintained in 85.7% (72/84) with no detection of M184V/I, 66.7% (8/12) with detection only at baseline, and 100% with detection only at week 96 (13/13) or both time points (12/12). Among those with M184V/I at both time points, the proportion of proviral sequences carrying the mutation increased from 30% to 45% (p = 0.0037).

Conclusions: Proviral-DNA M184V/I detection was not associated with virological outcomes in participants receiving DTG/3TC supporting its limited clinical value in this specific setting.

Background: Adherence to antituberculosis therapy is an important determinant of treatment outcome in rifampicin-resistant tuberculosis (RR-TB). Understanding adherence to contemporary treatment regimens in routine care is needed to support implementation in TB programs. We aimed to characterize temporal adherence patterns among people receiving oral treatment for RR-TB.

Methods: We conducted a prospective observational cohort study at a referral TB hospital in South Africa. People ≥15 years with pulmonary RR-TB starting an oral 9-12-month regimen were included. Treatment adherence was measured using a digital pillbox during ambulatory care and with directly observed therapy during hospital care. The primary outcome was proportion of adherence days through nine months. Latent class group-based trajectory modelling was used to identify temporal adherence patterns.

Results: 209/248 (84.3%) participants had assessable adherence data from the digital pillbox or directly observed therapy. Overall median adherence was 82% (IQR 63-98) with combined measures, and 72% (IQR 51-92) with digital pillbox only. Four distinct adherence patterns were identified. Adherence was 93-100% in the first month. Two groups, representing 136 (65.1%) individuals, had small reductions in adherence over time, separated by higher and lower early adherence. In the other two groups, there was a 50% reduction in adherence by months three (48/209, 23.0%) and six (25/209, 12.0%), respectively. Lower adherence over time was associated with having exclusive ambulatory care, treatment with the shorter regimen only, and age <40 years.

Conclusions: Treatment adherence declined over time in distinct temporal patterns. Group characteristics could identify individuals who may benefit from enhanced treatment support.

Doxycycline postexposure prophylaxis (doxy-PEP) is used to prevent chlamydia, syphilis, and gonorrhea infections in sexual and gender minority men and transgender women. We describe a systematic process for developing algorithms that allow for the identification of doxy-PEP prescriptions. Using an identified algorithm will allow improved monitoring of implementation and effectiveness.

Background: Before the advent of effective antiretroviral therapy, intensive care unit (ICU) admission rates for people with advanced human immunodeficiency virus HIV disease (AHD) were low, reflecting high mortality and limited treatment options. Despite improvements in ICU and HIV care, longitudinal outcome data in critically ill people with AHD are limited.

Methods: We performed a retrospective cohort study of ICU admissions in Australia and New Zealand between January 1993 and December 2022 in patients with a comorbid diagnosis of AHD. AHD was defined according to Acute Physiology and Chronic Health Assessment-IIIj (APACHE-IIIj), requiring an HIV diagnosis plus AHD-defining complication. Descriptive analysis was performed. Longitudinal changes in mortality were reported. Admissions were stratified by decade.

Results: There were 1505 ICU admissions with comorbid AHD over the study period. Between the first and third decades, the Sequential Organ Failure Score increased (median 3, interquartile range [IQR] 2-5 vs median 4, IQR 2-6, P < .001), as did patient age (median 41 years, IQR 34-52 vs median 53 years, IQR 44-63, P < .001). The proportion of patients with 1 or more chronic comorbidities using APACHE-IIIj scoring increased over time (18% vs 26%; P = .009). Crude hospital mortality reduced significantly from 36% in 1993-2002 to 14% in 2013-2022 (P < .001). Mortality improvements remained significant after adjustment for acute and chronic illness severity (using APACHE-IIIj risk of death) and hospital type (adjusted odds ratio of death by decade 0.43; 95% confidence interval, .35-.53).

Conclusions: Despite advances in HIV care, a subset of people with AHD require ICU admission. Mortality in this group has improved by more than 50%.

Background: Stagnating decreases in Kaposi sarcoma (KS) among men with HIV (MWH) following Treat-All policies necessitate evaluating changes in clinical drivers of KS. We examined clinical factors and their associations with KS rates among MWH in North America.

Methods: Among MWH in the North American AIDS Cohort Collaboration on Research and Design, we estimated annual KS rates (per 100 000 person-years [PY]) by viral suppression (<200 copies/mL), CD4 count (<500 vs ≥500 cells/mm3), and time since ART initiation (<1 year/naive vs ≥1 year) from 2009-2019. We quantified associations between clinical factors and KS rates using negative binomial regression, estimating incidence rate ratios (IRRs) with 95% CIs. Among MWH with KS, we estimated average annual percentage changes (AAPCs) in clinical factor distribution using joinpoint regression.

Results: There were 61 155 MWH (370 624 PY) contributing 262 KS diagnoses. KS decreased from 132 to 43 cases per 100 000 PY between 2009 and 2019. Viral suppression (IRR2009: .09 [95% CI: .04-.20]; IRR2019: .69 [.31-1.54]), recent/no ART initiation (IRR2009: .14 [.07-.30]; IRR2019: 1.16 [.53, 2.56]), and CD4 count ≥500 cells/mm3 (IRR2009: .13 [.05-.31]; IRR2019: .44 [.18-1.10]) were associated with reduced KS rates, attenuating over time. Unsuppressed viral load at KS diagnosis decreased by 10.6% (-15.8%, -4.8%) as did those on ART ≤1 year/naive (70%-40%; AAPC: -6.3% [-13.8%, 2.1%]).

Conclusions: Our findings underscore the importance of early HIV diagnosis/treatment in reducing KS burden. Attenuating associations with HIV factors indicate that those successfully managing HIV increasingly represent KS patients. KS drivers are evolving, requiring patient/population-level monitoring.