Clinical Infectious Diseases最新文献

Background: Longer-term outcome data following second-line antiretroviral therapy initiation in resource-limited settings is limited, especially in regions where genotypic resistance is inaccessible. This analysis evaluated extended efficacy and tolerability data from the D2EFT study.

Methods: D2EFT is a completed, multicenter, phase IIIB/IV, randomized, open-label trial in 14 low- and middle-income countries. People with human immunodeficiency virus (HIV) who had failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens were switched to 1 of ritonavir-boosted darunavir plus 2 nucleoside reverse transcriptase inhibitors (DRV/r + 2NRTIs), ritonavir-boosted darunavir plus dolutegravir (DTG + DRV/r), or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine (DTG + TDF/XTC), with or without pre-switch genotyping. Here we report virological suppression at 96 weeks, defined as HIV RNA <50 copies/mL in a modified intention-to-treat population.

Results: Between November 2017 and January 2022, 1190 participants were screened, 828 were randomized, and 826 were included in the analysis. At week 96, the proportions of participants with HIV RNA <50 copies/mL were 191/251 (76.1%) in DRV/r + 2NRTIs, 215/251 (85.7%) in DTG + DRV/r, and 231/283 (81.6%) in DTG + TDF/XTC. The treatment differences (95% confidence intervals [CIs]) in proportions achieving virological suppression were 9.6% (2.7, 16.4) in DTG + DRV/r and 9.0% (1.4, 16.6) in DTG + TDF/XTC, compared to DRV/r + 2NRTIs. Intermediate or high-level dolutegravir resistance was identified in 3/27 (13%) of virological failures in individuals taking DTG + TDF/XTC but in no one taking DTG + DRV/r. No darunavir resistance was observed.

Conclusions: After 96 weeks of follow-up, DTG + DRV/r and DTG + TDF/XTC demonstrated virological superiority over DRV/r + 2NRTIs after first-line NNRTI-failure. However, emerging dolutegravir resistance, which was observed only in individuals taking DTG + TDF/XTC, requires ongoing global surveillance.

Background: As coronavirus disease 2019 (COVID-19) is integrated into existing infectious disease control programs, it is important to understand the comparative clinical impact of COVID-19 and other respiratory diseases.

Methods: We conducted a retrospective cohort study of patients with symptomatic healthcare-associated COVID-19 or influenza reported to the nationwide, hospital-based surveillance system in Switzerland. Included patients were adults (aged ≥18 years) hospitalized for ≥3 days in tertiary care and large regional hospitals. Patients had COVID-19 symptoms and a real-time polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection ≥3 days after hospital admission between 1 February 2022 and 30 April 2023, or influenza symptoms and a real-time polymerase chain reaction-confirmed influenza A or B infection ≥3 days after hospital admission between 1 November 2018 and 30 April 2023. Primary and secondary outcomes were 30-day in-hospital mortality and admission to intensive care unit, respectively. Cox regression (Fine-Gray model) was used to account for time dependency and competing events, with inverse probability weighting to adjust for confounding.

Results: We included 2901 patients with symptomatic, healthcare-associated COVID-19 (Omicron) and 868 patients with symptomatic, healthcare-associated influenza from 9 hospitals. We found a similar case fatality ratio between healthcare-associated COVID-19 (Omicron) (6.2%) and healthcare-associated influenza (6.1%) patients; after adjustment, patients had a comparable subdistribution hazard ratio for 30-day in-hospital mortality (0.91; 95% confidence interval, .67-1.24). A similar proportion of patients were admitted to the intensive care unit (2.4% COVID-19; 2.6% influenza).

Conclusions: COVID-19 and influenza continue to cause severe disease among hospitalized patients. Our results suggest that in-hospital mortality risk of healthcare-associated COVID-19 (Omicron) and healthcare-associated influenza are comparable.

Background: Timely HIV diagnosis and treatment is critical to preventing transmission. The US Centers for Disease Control and Prevention (CDC) provides funding for HIV testing to local health departments and community organizations. We sought to estimate the number of additional HIV infections that would result from ending or interrupting CDC funding for HIV tests in US states.

Methods: We used a validated model of HIV transmission to simulate HIV epidemics in 18 US states. We projected incidence forward under three scenarios where all CDC-funded HIV testing ends in October 2025 and (1) never resumes, (2) returns to previous levels between January and December 2027, and (3) returns from January to December 2029. We calculated the excess incident HIV infections compared to a scenario where CDC-funded testing continues uninterrupted.

Results: If CDC funding for HIV tests were to end on October 1, 2025, we project 12,719 additional HIV infections across 18 states by 2030 (95% Credible Interval 4,547 to 21,896) - an increase of 10%. The projected effects varied by state, ranging from a 2.7% increase in Washington (1.0 to 4.7%) to a 29.9 increase in Louisiana (9.4 to 59.9%). States that perform more CDC-funded tests and states with more rural HIV epidemics were projected to see greater rises in incidence.

Conclusions: Disruptions to CDC-funded HIV testing would substantially increase new infections, particularly in states with more rural epidemics. These findings demonstrate the value of the CDC's HIV testing activities in curbing the spread of HIV in the US.

Background: Screening for syphilis increasingly relies on positive treponemal rather than nontreponemal tests (rapid plasma reagin [RPR]). We compared ocular syphilis in patients with nonreactive versus positive RPR.

Methods: We conducted a retrospective observational cohort study of ocular syphilis treated at 2 New England hospitals during 1996-2021 based on ophthalmologist-diagnosed eye findings and positive treponemal serology, regardless of RPR. We excluded patients with alternative diagnoses. We categorized RPR into nonreactive RPR, low-titer RPR (<1:8), and high-titer RPR (≥1:8) and compared early and long-term response to therapy.

Results: Our sample included 115 patients with ocular syphilis (median follow-up, 2.5 years): 25 (22%) with nonreactive RPR, 21 (18%) low-titer RPR, and 69 (60%) high-titer RPR. Compared with nonreactive and low-titer RPR, people with high-titer RPR were younger (mean 47 years, P < .001), more likely to be male (93%, P < .001) and more likely to be diagnosed with human immunodeficiency virus (49%, P < .001). People with nonreactive and low-titer RPR were less likely than those with high-titer RPR to have posterior uveitis/panuveitis (32% and 29% vs 75%, P < .001) or abnormal cerebrospinal fluid (26% and 35% vs 75%, P < .001), and more likely to present with chronic eye findings (20% and 29% vs 1%, P < .001). In long-term follow-up, eye findings improved and did not recur in most patients (62% nonreactive, 68% low-titer, 96% high-titer RPR); improved but recurred in 29%, 11%, and 4%, respectively; and were stable in 10%, 21%, and 0%, respectively.

Conclusions: Patients with ocular syphilis and nonreactive RPR are similar to patients with low-titer RPR, and antibiotic therapy is beneficial in most.

Background: We assessed the impact of pneumococcal conjugate vaccine (PCV) implementation on respiratory syncytial virus-positive, community-acquired alveolar pneumonia (RSV-CAAP) in young children in southern Israel.

Methods: This study was nested within a prospective population-based active surveillance system during 2004-2019. All children <60 months old residing in the region and served by the region's only hospital were included. A negative binomial regression model was used to evaluate the impact of PCV on the incidence of all-cause CAAP and RSV-CAAP and was the basis for estimating averted episodes.

Results: A total of 7640 all-cause CAAP episodes were observed; 50% were tested for RSV, of which 42% were positive. Shortly after PCV13 implementation, all-cause CAAP and RSV-CAAP rates markedly declined, stabilizing within 3-4 years. The mean annual hospitalization rates for all-cause CAAP and RSV-CAAP declined by 47% (95% CI: 40%-53%) and 29% (95% CI: -2% to 51%), respectively, during the late-PCV period, compared with the expected rates. This translated to a reduction in the mean annual incidence of 3.73 cases of all-cause CAAP/1000 children (95% CI: 2.98-4.58) and 0.50 cases of RSV-CAAP per 1000 children (95% CI: -.05 to 1.13). The highest incidences of averted cases occurred in children aged 12-23 months.

Conclusions: The observed dynamics of hospitalizations due to all-cause CAAP and RSV-CAAP following PCV implementation are consistent with the notion of a synergistic role of RSV and pneumococcus in CAAP in young children.