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Background People living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and prone to statin-related adverse events from drug-drug interactions with certain antiretroviral regimens. Objectives This study sought to evaluate the efficacy and safety of evolocumab in dyslipidemic PLHIV. Methods BEIJERINCK is a randomized, double-blind, multinational trial comparing monthly subcutaneous evolocumab 420 mg with placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia taking maximally-tolerated statin therapy. The primary endpoint was the percent change (baseline to week 24) in low-density lipoprotein cholesterol (LDL-C); secondary endpoints included achievement of LDL-C Results A total of 464 patients were analyzed (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). ASCVD was documented in 35.6% of patients, and statin intolerance/contraindications to statin use were present in 20.7% of patients. Evolocumab reduced LDL-C by 56.9% (95% CI: 61.6%, 52.3%) from baseline to week 24 versus placebo. An LDL-C level of Conclusions Evolocumab was safe and significantly reduced lipid levels in dyslipidemic PLHIV on maximally-tolerated statin therapy. Evolocumab is an effective therapy for lowering atherogenic lipoproteins in PLHIV with high cardiovascular risk.

People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52 weeks in PWH.This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420 mg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24 weeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART.Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined.Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP.Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events.NCT02833844.http://links.lww.com/QAD/C441.

Treatment of Stenotrophonomas maltophilia infections is difficult due to its predilection to form biofilms and susceptibility to a limited number of antibiotics. We report a case of S. maltophilia-associated periprosthetic joint infection successfully treated with a combination of the novel therapeutic agent, cefiderocol, and trimethoprim-sulfamethoxazole after debridement and implant retention.

Highlights • 22.5% of adult patients with H1N1 developed bacterial co-infection. • Staphylococcus aureus was the most common cause of co-infection. • Bacterial and viral co-infections were associated with death in bivariate. • Patients with a bacterial co-infection had greater use of resources., Background Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. Objectives To describe the spectrum and clinical impact of co-infections. Study design Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. Results Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23–0.73], p = 0.003), leukocytosis (>11 K/μl, OR 3.7 [2.2–6.2], p

Human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) sequences were characterized from six mother-infant pairs following vertical transmission. The LTR sequences exhibited a low degree of heterogeneity within mothers, within infants, and between epidemiologically linked mother-infant pairs. However, LTR sequences were more heterogeneous between epidemiologically unlinked individuals compared with linked mother-infant pairs. These data were further supported by low estimates of genetic diversity and clustering of each mother-infant pair's sequences into a separate subtree as well as the presence of common signature sequences between mother-infant pairs. The functional domains essential for LTR (promoter) function, including the promoter (TATAA), enhancers (three Sp-I and two NF-kappaB), the modulatory regions (two AP-I sites, two NFAT, one NF-IL6 site, one Ets-1, and one USF-1), and the TAR region were generally conserved among mother-infant pairs. Taken together, limited heterogeneity and conservation of functional domains in the LTR following vertical transmission support the notion that a functional LTR is critical in viral replication and pathogenesis in HIV-1-infected mothers and their infected infants.

Author(s): Shah, Nirav S; Greenberg, Jared A; McNulty, Moira C; Gregg, Kevin S; Riddell, James; Mangino, Julie E; Weber, Devin M; Hebert, Courtney L; Marzec, Natalie S; Barron, Michelle A; Chaparro-Rojas, Fredy; Restrepo, Alejandro; Hemmige, Vagish; Prasidthrathsint, Kunatum; Cobb, Sandra; Herwaldt, Loreen; Raabe, Vanessa; Cannavino, Christopher R; Hines, Andrea Green; Bares, Sara H; Antiporta, Philip B; Scardina, Tonya; Patel, Ursula; Reid, Gail; Mohazabnia, Parvin; Kachhdiya, Suresh; Le, Binh-Minh; Park, Connie J; Ostrowsky, Belinda; Robicsek, Ari; Smith, Becky A; Schied, Jeanmarie; Bhatti, Micah M; Mayer, Stockton; Sikka, Monica; Murphy-Aguilu, Ivette; Patwari, Priti; Abeles, Shira R; Torriani, Francesca J; Abbas, Zainab; Toya, Sophie; Doktor, Katherine; Chakrabarti, Anindita; Doblecki-Lewis, Susanne; Looney, David J; David, Michael Z | Abstract: BackgroundInfluenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season.MethodsA retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.ResultsA total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (g65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], Pl.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], Pl.001).ConclusionRisk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.

Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America. After successful vector control programs, congenital transmission remains as a challenge to disease elimination. We used the PRECEDE-PROCEED planning model to develop strategies for neonatal screening of congenital Chagas disease in rural communities of Guatemala. These communities have persistent high triatomine infestations and low access to healthcare. We used mixed methods with multiple stakeholders to identify and address maternal-infant health behaviors through semi-structured interviews, participatory group meetings, archival reviews and a cross-sectional survey in high risk communities. From December 2015 to April 2016, we jointly developed a strategy to illustratively advertise newborn screening at the Health Center. The strategy included socioculturally appropriate promotional and educational material, in collaboration with midwives, nurses and nongovernmental organizations. By March 2016, eight of 228 (3.9%) pregnant women had been diagnosed with T. cruzi at the Health Center. Up to this date, no neonatal screening had been performed. By August 2016, seven of eight newborns born to Chagas seropositive women had been parasitologically screened at the Health Center, according to international standards. Thus, we implemented a successful community-based neonatal screening strategy to promote congenital Chagas disease healthcare in a rural setting. The success of the health promotion strategies developed will depend on local access to maternal-infant services, integration with detection of other congenital diseases and reliance on community participation in problem and solution definition., Author summary Chagas disease is caused by a parasite transmitted by insects that infest households living in extreme poverty conditions. The parasite can also be transmitted from mother to child during pregnancy. If detected at birth, the infection can be treated effectively with available drugs. However, access to professional neonatal healthcare is limited in rural communities such as those affected by Chagas disease. We developed a strategy to promote access to a simple neonatal diagnostic test in a rural region of Guatemala considered at risk for Chagas disease. The strategy included collaboration between Health Center personnel, midwives and non-governmental organizations that play a local role in maternal-infant care. During the implementation of a health promotion campaign, screening revealed previous infection in almost one of every 25 pregnant women. Most babies born to positive women were tested at the Health Center for parasites in blood. The implementation of similar strategies to prevent congenital Chagas in other rural areas should consider local maternal-infant care practices. This strategy of collaboration between Ministry of Health, community health workers, non-government organizations, academia and external governmental support could be expanded to screen for other diseases, such as Zika, that require early detection to improve overall infant health.