Perspectives on a peer-driven intervention to promote pre-exposure prophylaxis (PrEP) uptake among men who have sex with men in southern New England: a qualitative study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities. METHODS: We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection. RESULTS: Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects. CONCLUSIONS: Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.

Perceived Versus Actual Costs of HIV Pre-Exposure Prophylaxis Among Gay, Bisexual, and Other Men Who Have Sex with Men in the United States.

Gay, bisexual, and other men who have sex with men (GBMSM) account for the highest proportion of HIV diagnoses in the United States, with daily pre-exposure prophylaxis (PrEP) significantly reducing transmission risk. Since 2021, the Affordable Care Act rules have required PrEP and accompanying care visits to be free for most Americans; nevertheless, insurers have found ways to circumvent no-cost PrEP and some employers are receiving exemptions from including it in their formularies. Despite this, perceived costs and indirect expenses still hinder PrEP adoption. This study examines the differences between perceived and actual costs among GBMSM who have and have not used PrEP. We conducted a one-time online survey with 692 adults from six New England states between May 2020 and October 2021. Participants who had never used PrEP estimated its cost, while those with prior PrEP experience reported their actual expenses. Bivariate analysis and multi-variable logistic regression were used to assess the data. Results showed a 60% difference between perceived ($48) and actual ($30) median monthly costs. Higher perceived costs among nonusers were linked to race and income, while high actual costs for prior users were associated with insurance type, income, wealth, race, and self-rated consumer credit. This significant disparity in PrEP cost perceptions highlights the need for targeted outreach and messaging to improve PrEP uptake among at-risk populations who have not yet accessed it.

Enhanced Nitric Oxide Delivery Through Self-Assembling Nanoparticles for Eradicating Gram-Negative Bacteria.

In the current battle against antibiotic resistance, the resilience of Gram-negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self-assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1-2.8 µg mL-1), which is at least ten times lower than the reported data for NO donors (≥200 µg mL-1). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self-assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next-generation antimicrobial agents.

"Why Not Just go on PrEP?": A Study to Inform Implementation of an HIV Prevention Intervention Among Hispanic/Latino Men Who Have Sex With Men in the Northeastern United States.

BACKGROUND: Preexposure prophylaxis (PrEP) is an effective biological option for HIV prevention yet persistent disparities in PrEP uptake and retention exist among Hispanic/Latino men who have sex with men (MSM). We evaluated barriers and facilitators to PrEP care among Hispanic/Latino MSM at risk for and living with HIV. SETTING: A small urban setting in the Northeastern United States. METHODS: This was a mixed-methods, exploratory, sequential, qualitative and quantitative pilot study among Latino MSM at-risk and/or living with HIV across (1) semistructured qualitative interviews (N = 15) and (2) cross-sectional survey (N = 98). RESULTS: Participants reported a diverse range of sexual identities, HIV statuses, and PrEP statuses. Qualitative participants described feelings of isolation in both Hispanic/Latino and queer communities that made it challenging to learn about HIV prevention or PrEP from peers. Participants in the survey indicated that they would be more inclined to uptake PrEP if PrEP were offered in primary care settings (n = 61; 62.2%); there were specific LGBTQ+ affirming medical settings (n = 36; 36.7%); and/or they could meet other people who are currently on PrEP and sharing experiences online (n = 46; 46.9%) or in person (n = 38; 38.8%). Findings were organized to reflect determinants and implementation strategies that could be used to improve PrEP uptake among this population. CONCLUSIONS: This mixed-methods study identified several challenges and opportunities for increasing the reach of PrEP to Hispanic/Latino MSM. These findings should be used to inform tailored implementation strategies to promote PrEP uptake among this at-risk yet currently underserved population.

Symptoms and Health-Related Quality of Life Among Older Adults Living With HIV.

BACKGROUND: As individuals living with HIV age, they often experience both physical and psychological symptoms-along with potential reductions in social support-which can significantly affect their health-related quality of life (HRQOL)-a crucial measure in HIV care. However, research exploring the potential predictive roles of social support and symptom experiences in HRQOL among older people living with HIV (PLWH) is limited. OBJECTIVES: This cross-sectional study aimed to investigate relationships between social support, symptom experiences, and HRQOL in older adults with HIV. METHODS: Older adults with HIV aged ≥50 years completed surveys on demographic and HIV-related characteristics, social support, four symptoms, and HRQOL. Hierarchical multiple linear regression analyses were used to determine predictors for six HRQOL domains. RESULTS: Among the 141 PLWH, significant associations were found between fatigue and health perceptions, physical functioning, and role functioning. Sleep disturbance was a significant predictor of health perceptions and social functioning. Anxiety displayed associations with physical functioning, role functioning, mental health, and pain. Depression was linked to health perceptions and mental health aspects of HRQOL. Notably, social support was not associated with any HRQOL domains. DISCUSSION: These findings underscore the importance of assessing a range of common symptoms to enhance HRQOL among older adults living with HIV, necessitating tailored symptom management strategies for this growing population.

Identifying Effective Components of a Social Marketing Campaign to Improve Engagement With Express Sexual Health Services Among Gay, Bisexual, and Other Men Who Have Sex With Men: Case Study.

Background: Little is known about how best to reach people with social marketing messages promoting use of clinical HIV and sexually transmitted infection (STI) services. Objective: We evaluated a multiplatform, digital social marketing campaign intended to increase use of HIV/STI testing, treatment, and prevention services among gay, bisexual, and other men who have sex with men (MSM) at an LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and/or questioning) community health center. Methods: We evaluated engagement with a social marketing campaign launched by Open Door Health, the only LGBTQ+ community health center in Rhode Island, during the first 8 months of implementation (April to November 2021). Three types of advertisements encouraging use of HIV/STI services were developed and implemented on Google Search, Google Display, Grindr, and Facebook. Platforms tracked the number of times that an advertisement was displayed to a user (impressions), that a user clicked through to a landing page that facilitated scheduling (clicks), and that a user requested a call to schedule an appointment from the landing page (conversions). We calculated the click-through rate (clicks per impression), conversion rate (conversions per click), and the dollar amount spent per 1000 impressions and per click and conversion. Results: Overall, Google Search yielded the highest click-through rate (7.1%) and conversion rate (7.0%) compared to Google Display, Grindr, and Facebook (click-through rates=0.4%-3.3%; conversion rates=0%-0.03%). Although the spend per 1000 impressions and per click was higher for Google Search compared to other platforms, the spend per conversion-which measures the number of people intending to attend the clinic for services-was substantially lower for Google Search (US $48.19 vs US $3120.42-US $3436.03). Conclusions: Campaigns using the Google Search platform may yield the greatest return on investment for engaging MSM in HIV/STI services at community health clinics. Future studies are needed to measure clinical outcomes among those who present to the clinic for services after viewing campaign advertisements and to compare the return on investment with use of social marketing campaigns relative to other approaches.

Clinician Specialty and HIV PrEP Prescription Reversals and Abandonments.

Importance: Clinicians are a key component of preexposure prophylaxis (PrEP) care. Yet, no prior studies have quantitatively investigated how PrEP adherence differs by clinician specialty. Objective: To understand the association between prescribing clinician specialty and patients not picking up (reversal/abandonment) their initial PrEP prescription. Design, Setting, and Participants: This cross-sectional study of patients who were 18 years or older used pharmacy claims data from 2015 to 2019 on new insurer-approved PrEP prescriptions that were matched with clinician data from the US National Plan and Provider Enumeration System. Data were analyzed from January to May 2022. Main Outcomes and Measures: Clinician specialties included primary care practitioners (PCPs), infectious disease (ID), or other specialties. Reversal was defined as a patient not picking up their insurer-approved initial PrEP prescription. Abandonment was defined as a patient who reversed and still did not pick their prescription within 365 days. Results: Of the 37 003 patients, 4439 (12%) were female and 32 564 (88%) were male, and 77% were aged 25 to 54 years. A total of 24 604 (67%) received prescriptions from PCPs, 3571 (10%) from ID specialists, and 8828 (24%) from other specialty clinicians. The prevalence of reversals for patients of PCPs, ID specialists, and other specialty clinicians was 18%, 18%, and 25%, respectively, and for abandonments was 12%, 12%, and 20%, respectively. After adjusting for confounding, logistic regression models showed that, compared with patients who were prescribed PrEP by a PCP, patients prescribed PrEP by ID specialists had 10% lower odds of reversals (odds ratio [OR], 0.90; 95% CI, 0.81-0.99) and 12% lower odds of abandonment (OR, 0.88; 95% CI, 0.78-0.98), while patients prescribed by other clinicians had 33% higher odds of reversals (OR, 1.33; 95% CI, 1.25-1.41) and 54% higher odds of abandonment (OR, 1.54; 95% CI, 1.44-1.65). Conclusion: The results of this cross-sectional study suggest that PCPs do most of the new PrEP prescribing and are a critical entry point for patients. PrEP adherence differs by clinician specialties, likely due to the populations served by them. Future studies to test interventions that provide adherence support and education are needed.

Rhodium(I)-Catalyzed Cascade Annulation of 1,n-Diynyl Nitrones to 3,4-Fused Fully Substituted Furans.

A method for the assembly of fully substituted furans containing a 3,4-fused 5-8-membered carbocycle, heterocycle, or spirocycle from rhodium(I)-catalyzed and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)-assisted cascade annulation of 1,n-diynyl nitrones has been developed.

The effects of regular home delivery of HIV self-testing and follow-up counselling on HIV testing and prevention outcomes in men who have sex with men who test infrequently in the United States: a pragmatic, virtual randomized controlled trial.

INTRODUCTION: Past research shows that HIV self-testing (HIVST) can increase testing and facilitate more HIV diagnoses relative to clinic testing. However, in the United States, the use of HIVSTs is limited due to concerns that those who use HIVST could be less likely to be linked to care. METHODS: From January 2019 to April 2022, we recruited 811 men who have sex with men (MSM) in the United States who tested infrequently using an online marketing campaign and randomized them 1:1:1 to receive one of the following every 3 months for a year: (1) text message reminders to get tested at a local clinic (control); (2) mailed HIVST kits with access to a free helpline (standard HIVST); and (3) mailed HIVST kits with counselling provided within 24 hours of opening a kit (eTest). Quarterly follow-up surveys assessed HIV testing, sexually transmitted infection (STI) testing, pre-exposure prophylaxis (PrEP) use and sexual risk behaviour. FINDINGS: Eight participants were diagnosed with HIV, and all but one were through HIVST. Participants in either HIVST condition, standard or eTest, had significantly higher odds of any testing (OR = 7.9, 95% CI = 4.9-12.9 and OR = 6.6, 95% CI = 4.2-10.5) and repeat testing (>1 test; OR = 8.5, 95% CI = 5.7-12.6; OR = 8.9, 95% CI = 6.1-13.4) over 12 months relative to the control group. Rates of STI testing and PrEP uptake did not differ across study condition, but those in the eTest condition reported 27% fewer sexual risk events across the study period relative to other groups. CONCLUSIONS: HIVST vastly increased testing, encouraged more regular testing among MSM, and identified nearly all new cases, suggesting that HIVST could diagnose HIV acquisition earlier. Providing timely follow-up counselling after HIVST did not increase rates of STI testing or PrEP use, but some evidence suggested that counselling may have reduced sexual risk behaviour. To encourage more optimal testing, programmes should incorporate HIVST and ship kits directly to recipients at regular intervals.

Long-Term HIV Pre-Exposure Prophylaxis Persistence and Reinitiation in Connecticut from 2012 to 2018.

HIV pre-exposure prophylaxis (PrEP) is a highly effective biomedical prevention for HIV infections. PrEP persistence is critical to achieving optimal protection against HIV infection. However, little is known about PrEP persistence in the United States. This study utilized the Connecticut All-Payer Claims Database (APCD) to identify PrEP persistence among patients who filled their PrEP prescriptions in the state. The authors identified 1,576 PrEP patients who picked up PrEP prescriptions and extracted medical and pharmacy claims to evaluate a longitudinal cohort during 2012-2018 based on the Connecticut APCD. Patients who did not pick up medication for one consecutive month (ie, 30 days) were defined as discontinuing PrEP. Kaplan-Meier Survival Curve and proportional hazard regression were used to describe PrEP persistence. Of the 1,576 patients who picked up PrEP prescriptions, the median age was 32.0 (interquartile range [IQR]: 22.0-44.0). The majority were male individuals (93%). Of 1,040 patients who discontinued PrEP, 702 (67.5%) restarted PrEP at least once. The median time of PrEP persistence was 3 months (IQR: 1-6 months) for initial PrEP use. The median time on PrEP was also around 3 months in the following episodes of PrEP use. Being female, being on parent's insurance, and having high co-pays were associated with shorter periods of PrEP persistence. PrEP persistence was low among patients who picked up PrEP prescriptions. Although many patients restarted PrEP, persistence remained low during follow-up PrEP use and possibly led to periods of increased HIV risk. Effective interventions are needed to improve PrEP persistence and reduce HIV incidence.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

BACKGROUND: Bivalent SARS-CoV-2 vaccines were developed to counter increasing susceptibility to emerging SARS-CoV-2 variants. We evaluated the durability of immunity and protection following first bivalent vaccination among nursing home residents. METHODS: We evaluated anti-spike and neutralization titers from blood in 653 community nursing home residents before and after each monovalent booster, and a bivalent vaccine. Concurrent clinical outcomes were evaluated using electronic health record data from a separate cohort of 3783 residents of Veterans Affairs (VA) nursing homes who had received at least the primary series monovalent vaccination. Using target trial emulation, we compared VA residents who did and did not receive the bivalent vaccine to measure vaccine effectiveness against infection, hospitalization, and death. FINDINGS: In the community cohort, Omicron BA.5 neutralization activity rose after each monovalent and bivalent booster vaccination regardless of prior infection history. Titers declined over time but six months post-bivalent vaccination, BA.5 neutralization persisted at detectable levels in 75% of infection-naive and 98% of prior-infected individuals. In the VA nursing home cohort, bivalent vaccine added effectiveness to monovalent booster vaccination by 18.5% for infection (95% confidence interval (CI) -5.6, 34.0%), and 29.2% for hospitalization or death (95% CI -14.2, 56.2%) over five months. INTERPRETATION: The level of protection declined after bivalent vaccination over a 6 month period and may open a window of added vulnerability before the next updated vaccine becomes available, suggesting a subset of nursing home residents may benefit from an additional vaccination booster. FUNDING: CDC, NIH, VHA.

Factors Correlated with Anticoagulation Choice in Primary Care Patients with Atrial Fibrillation and High Stroke Risk.

BACKGROUND: The available data on anticoagulation therapy in real-world primary care settings for atrial fibrillation (AF) patients at high risk of stroke is limited. OBJECTIVE: To evaluate anticoagulation therapy and elucidate the factors associated with the selection between direct oral anticoagulants (DOACs) and warfarin. DESIGN AND PARTICIPANTS: This is a retrospective cohort study that included patients ≥ 18 years old at a large primary care outpatient group, a network of twenty clinics in the northeast United States between January 4, 2021 - January 4, 2023. MAIN MEASURES: Oral anticoagulation therapy in AF patients with high risk of stroke (CHA2DS2-VASc score of ≥ 2 in men or ≥ 3 in women). KEY RESULTS: Among the 3,118 adult patients with AF and high risk of stroke (median age 77.90, IQR 71.66-84.50 years; male 57.6%), we found that older age (aOR 1.40, p = 0.003), greater BMI (25-29.9: aOR 1.32, p = 0.048; ≥ 30 aOR 1.42, p = 0.010), and taking more than five medications (aOR 2.28, p < 0.001) were more likely to be on an oral anticoagulant. Among those taking an OAC, having Medicare as the sole coverage (aOR 0.53, p = 0.032), male gender (aOR 0.69, p = 0.011), worse renal function (aOR 0.80, p = 0.021), and higher CHA2DS2-VASc score (aOR 0.88, p = 0.024) are more likely to be on warfarin than a DOAC. Patients taking more than five medications daily (6-10 medications: aOR 1.92, p = 0.013; ≥ 16: aOR = 2.10, p = 0.006) were more likely to be on an anticoagulant and may receive a DOAC over warfarin. CONCLUSIONS: AF with high stroke risk adult patients are more likely to be on an oral anticoagulant if they are older, having BMI ≥ 25, or taking more than five medications. Medicare as the sole coverage, male gender, worse renal function, and higher CHA2DS2-VASc scores are factors associated with greater warfarin usage, while patients taking over five daily medications are more likely to be prescribed DOACs.

CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024.

No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.

Early adopters of doxycycline as post-exposure prophylaxis to prevent bacterial sexually transmitted infections in a real-world clinical setting.

OBJECTIVES: Doxycycline as post-exposure prophylaxis (DoxyPEP) is a novel prevention approach which has demonstrated efficacy in preventing bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW) including people who are living with HIV and those on HIV pre-exposure prophylaxis (PrEP). We evaluated patient knowledge and interest in DoxyPEP, as well as early adopters of its use. METHODS: In 2023, patients presenting for HIV and STI services at a primary care and sexual health clinic were asked about DoxyPEP knowledge, interest and use. Bivariate and multivariate analyses were used to evaluate demographics and behaviours associated with these outcomes. RESULTS: A total of n=421 people presented for care. Of these, 314 were MSM/TGW. Fifteen percent were Black/African-American, and 21% were Hispanic/Latino. A total of 50% of MSM/TGW had heard of DoxyPEP, 49% were interested and 18% reported prior DoxyPEP use. Having a history of STI infection ever (adjusted OR (aOR) 5.95, 95% CI 2.69 to 13.13) and in the past 12 months (aOR 2.99, 95% CI 1.56 to 5.72) were both associated with DoxyPEP use. Individuals who had ever used HIV PrEP had nearly three times the odds of ever taking DoxyPEP (aOR 2.88, 95% CI 1.56 to 5.30). There was no association between the use of DoxyPEP and race, ethnicity or HIV status. CONCLUSIONS: Among MSM and TGW, there is already significant awareness, interest and use of DoxyPEP to prevent bacterial STIs. Public health efforts should focus on improving access and delivery of this STI prevention intervention to MSM and TGW.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

Enantioselective and Regiodivergent Gold and Chiral Brønsted Acid Catalyzed Cycloisomerization/Diels-Alder Reaction of 1,10-Dien-4-yn-3-yl Acetates: Synthesis of Norbornene-Embedded Tricarbocycles.

A synthetic method for the enantioselective and regiodivergent synthesis of hexahydro-2H-2,4a-methanonaphthalen-4-yl and octahydro-2,4-methanoazulen-1-yl esters that relies on the gold(I)- and chiral Brønsted acid-catalyzed cycloisomerization/Diels-Alder (CDA) reaction of (E)-1,10-dien-4-yn-3-yl acetates is described.

Gold-Catalyzed Double Spirocyclization of 3-Ene-1,7-diyne Esters to Dispiroheterocycles.

A synthetic method to prepare dispiroheterocycles containing two all-carbon quaternary centers efficiently that relies on the gold(I)-catalyzed double spirocyclization of 3-ene-1,7-diyne esters is described. The suggested mechanism delineates a rare example of a dispirocyclization featuring two 1,n-acyloxy shifts comprising a 1,3-acyloxy migration and an interrupted 1,5-acyl migration that was achieved with the assistance of residual water in the reaction media.

HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS: Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

Integration of Partner Notification Services at a Sexually Transmitted Infections Clinic.

OBJECTIVES: PNS is critical to prevent the spread of STIs. We evaluated the feasibility of integrating PNS into an STI clinic focused on MSM. DESIGN/METHODS: The RI STI Clinic, in partnership with the RIDOH, implemented a PNS program in 2019. Interviews with patients diagnosed with gonorrhea/ syphilis were conducted. RIDOH attempted outreach to partners identified. We utilized interview data among MSM diagnosed with gonorrhea/syphilis in clinic from 1/1/19-12/31/2021. Bivariate analyses/multivariable logistic regression were conducted. RESULTS: 341 MSM were diagnosed with gonorrhea/syphilis during the three-year period, and 233 (68%) interviews were completed. Partner information was provided in 173 (74%) interviews. At least one workable partner was provided in 110 (47%) interviews. No statistically significant associations between provision of workable partners and index patient age/race/ethnicity were found. CONCLUSIONS: PNS at an STI clinic was successful, but challenges led to suboptimal information. Research is needed to identify barriers to integrate/optimize PNS in STI clinics.