Machine learning (ML) algorithms may be effective at improving the HCV care cascade. One ML algorithm, developed using U.S. ambulatory electronic medical records (EMR), demonstrated the ability to identify people infected with HCV earlier than conventional testing strategies among those with indications for screening. We evaluated the potential cost-effectiveness of ML-enabled screening for the early identification of undiagnosed HCV among people in care in the U.S. An HCV natural history Markov model was developed to evaluate the cost-effectiveness of the ML algorithm-enabled screening compared to conventional testing over the training data period. Based on the training data, the ML algorithm identified patients on average 6.5 months earlier than conventional testing strategies. We compared the status quo to intervention scenarios using the ML algorithm at different recall levels (proportion of HCV patients identified, 5-100%). We identified the optimal algorithm recall level, which maximized health (measured in quality-adjusted life years, QALYs) while staying under a willingness-to-pay threshold of USD$100,000/QALY gained. ML-enabled screening was cost-effective (ICER < $100 k/QALY gained) in identifying undiagnosed HCV patients for recall levels up to 30%. The optimal recall level was 30% (Precision 0.27%), which resulted in a mean ICER of $94,022/QALY gained. ML-enabled screening for the early identification of undiagnosed HCV patients could be cost-effective in the U.S. Prospective evaluation of real-world effectiveness is warranted.

Respiratory syncytial virus (RSV) vaccine clinical trials reported higher frequencies of atrial fibrillation in intervention compared with control groups. In this large, population-based, propensity-matched study, we found that RSV vaccine was not associated with increased risk of new-onset or recurrent atrial fibrillation within 1-42 days, compared with influenza or tetanus, diphtheria, and pertussis (Tdap) vaccines.

OBJECTIVE:To evaluate virological outcomes of people with HIV (PWH) and adherence challenges to oral antiretroviral therapy (ART) who initiate long-acting injectable ART. DESIGN:Observational cohort study. SETTING:Single-center urban HIV primary care clinic at the University of California San Diego. PARTICIPANTS:All PWH who initiated long-acting injectable (LAI)-ART between November 2021 and September 2023 with documented adherence challenges to oral ART. MAIN OUTCOME MEASURES:The primary outcomes were virologic failure (two consecutive viral loads ≥200 copies/ml, one viral load ≥1000 copies/ml, or one viral load ≥200 copies/ml with evidence of resistance mutation to LAI-ART ≥30 days after initiation of LAI-ART) or discontinuation of LAI-ART for any reason within 96 weeks of initiation. RESULTS:Of the 62 eligible individuals, 48 (77.4%) remained virologically suppressed on LAI-ART and 14 (22.6%) discontinued therapy by 96 weeks. Of these 14 individuals, 3 experienced virologic failure (at 28, 40, and 42 weeks) and 3 were lost to follow-up. There were similar outcomes among the 26 participants with active substance use, of whom 18 (69%) remained suppressed on LAI-ART at 96 weeks. The remaining participants discontinued LAI-ART due to preference, adverse events, insurance issues, or death. CONCLUSION:High rates of viral suppression were achieved and maintained at 96 weeks, supporting the use of LAI-ART among those with adherence challenges to oral ART, including those with significant barriers to care, including substance use disorder and psychiatric comorbidities.

Long-acting injectable cabotegravir/rilpivirine (LAI-CAB/RPV) may improve outcomes among persons with human immunodeficiency virus (PWH) with adherence difficulties to oral therapy. In this real-world observational study, over 85% of PWH remained on therapy and virally suppressed 48 weeks after initiating LAI-CAB/RPV. Providers should consider LAI therapy among PWH with adherence difficulties.

Introduction: Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is being used to mitigate disease in the current global mpox outbreak, but a global vaccine shortage may limit large scale vaccination.Methods: Participants were randomized 1:1:1 to receive two doses of MVA-BN administered 28 days apart: intradermal (ID) 2 × 107 TCID50 (2 × 107 ID), ID 1 × 107 TCID50 (1 × 107 ID), or standard dose subcutaneous (SC) 1 × 108 TCID50 (1 × 108 ID). The primary objective was non-inferiority testing of each ID regimen compared to the standard SC regimen using vaccinia virus plaque reduction neutralizing titer assay (PRNT) geometric mean titers (GMT) at Day 43 (2 weeks post-second vaccination). Secondary objectives were non-inferiority testing of individual peak humoral immune responses, comparison of humoral immune responses, vaccinia virus-specific PRNT half-life (t½), and safety.Results: Day 43 non-inferiority by PRNT GMT was established for the 2 × 107 ID regimen but not the 1 × 107 ID regimen. The 2 × 107 ID regimen was also non-inferior to the SC dose at Days 15 and 29, prior to the second dose; the 1 × 107 ID regimen did not meet the non-inferiority criteria at any point post-vaccination. The three study regimens had similarly high seroconversion rates and similar anti-vaccinia PRNT half-lives.Most participants experienced injection site and systemic reactogenicity of moderate severity or less and only mild unsolicited adverse events (mostly skin discoloration and nodules at the injection site).Conclusion: The 2 × 107 ID regimen, but not the 1 × 107 ID regimen, was non-inferior to the SC regimen on Day 43. The study supports use of the 2 × 107 ID regimen if needed.Clinicaltrials.gov NCT05512949

BACKGROUND:Covid-19 vaccines are updated to match circulating strains based on reasoning that better strain-matched immunogenicity should provide better protection. Randomized evidence with disease endpoints to support strain matching is lacking. We evaluated COVID-19 incidence among adults randomized to a second booster of Prototype or Omicron-based vaccines. METHODS:COVAIL was a four-stage Phase 2 clinical trial; results from Stages 1 (mRNA-1273 [Moderna]) and 2 (BNT162b2 [Pfizer/BioNTech]) are described here. Adults who had received a primary series and one booster of an authorized COVID-19 vaccine were eligible. Participants received one dose of either Prototype vaccine or a monovalent or bivalent Omicron BA.1 vaccine. SARS-CoV-2 neutralization titers (ID50) were measured pre- and post-vaccination. Covariate-adjusted cumulative COVID-19 incidence and Cox regression analyses were conducted separately for each stage. RESULTS:706 participants with pre- and day 15 post-vaccination ID50 titers (n = 503 in Stage 1, n = 203 in Stage 2) were included. Within stages, participant characteristics and baseline ID50 titers were similar between Prototype and Omicron-based arms. There was no difference in cumulative COVID-19 incidence for Prototype vs. Omicron-based vaccine in Stage 1 (RR 1.04, 95 % CI 0.73-1.48), while incidence was higher among Prototype recipients in Stage 2 (RR 2.56, 1.44-4.52). Cox regression analysis showed no difference in Stage 1 (HR 1.04, 0.68-1.58), but higher incidence for Prototype recipients in Stage 2 (HR 2.95, 1.52-5.72). CONCLUSIONS:Omicron-based vaccines as second boosters were more protective against COVID-19 relative to Prototype among those receiving BNT162b2 but not mRNA-1273. Differences between stages such as force of infection, antigen matching, and vaccine differences may explain this finding. CLINICALTRIALS:govRegistry Number: NCT05289037.

BACKGROUND:Effective antiretroviral therapy to maintain durable viral suppression is key to ending the HIV epidemic in the United States. We evaluated the ability of machine learning algorithms to predict people with HIV (PWH) at risk of unsuppressed viral load. SETTING:Retrospective study among PWH from San Diego County (n = 18,916). The study used reported public health HIV data (2017-2022) to predict the outcome of HIV viral load >200 copies/mL during a year-long prediction window. METHODS:The data was partitioned by calendar date into two training and one validation datasets to accurately assess performance for predicting future observations. A random forest model was used to generate outcome predictions for the overall population and stratified by race. Mediation analysis was undertaken to assess underlying causality. RESULTS:The model had an area under the receiver operating characteristic curve of 82.2 (95% CI: 79.3 to 85.0), a sensitivity of 33.8% (95% CI: 28.6 to 39.0), and specificity of 96.9% (95% CI: 95.7 to 97.2) corresponding to a positive predictive value of 55.7% (95% CI: 48.7 to 62.8) and negative predictive value of 91.7% (95% CI: 90.6 to 92.8). The area under the receiver operating characteristic was similar across races. Prior viral load characteristics were identified as the most important variables; however, they partially acted as mediators of underlying demographic (eg, race) and HIV infection risk (eg, injection drug use). CONCLUSIONS:Machine learning algorithms using mandatory reported public health HIV data can predict which PWH will have future unsuppressed viral load. Future work will assess its clinical utility compared to existing data-to-care initiatives.

Long-acting injectable cabotegravir/rilpivirine (LAI-CAB/RPV) may improve outcomes among persons with human immunodeficiency virus (PWH) with adherence difficulties to oral therapy. In this real-world observational study, over 85% of PWH remained on therapy and virally suppressed 48 weeks after initiating LAI-CAB/RPV. Providers should consider LAI therapy among PWH with adherence difficulties.

Background Standard-of-care nucleic acid amplification tests (routine NAATs) for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) can take several days to result and therefore delay treatment. Rapid point-of-care GC/CT NAAT (rapid NAAT) could reduce the time to treatment and therefore onward transmission. This study evaluated the incremental cost per infectious day averted and overall cost of implementation associated with rapid compared with routine NAAT. Methods Prospective sexually transmitted infection (STI) treatment data from men who have sex with men and transgender women in San Diego who received rapid NAAT between November 2018 and February 2021 were evaluated. Historical time from testing to treatment for routine NAAT was abstracted from the literature. Costs per test for rapid and routine NAAT were calculated using a micro-costing approach. The incremental cost per infectious day averted comparing rapid to routine NAAT and the costs of rapid GC/CT NAAT implementation in San Diego Public Health STI clinics were calculated. Results Overall, 2333 individuals underwent rapid NAAT with a median time from sample collection to treatment of 2 days compared with 7 to 14 days for routine NAAT equating to a reduction of 5 to 12 days. The cost of rapid and routine GC/CT NAAT was $57.86 and $18.38 per test, respectively, with a cost-effectiveness of between $2.43 and $5.82 per infectious day averted. The incremental cost of rapid NAAT improved when at least 2000 tests were performed annually. Conclusions Although rapid GC/CT NAAT is more expensive than routine testing, the reduction of infectious days between testing and treatment may reduce transmission and provide improved STI treatment services to patients.

BACKGROUND:Many persons with HIV remain out of care (PWH-OOC). We evaluated InstaCare, a complex intervention integrating the brief behavioral intervention 60 minutes for Health with the rapid restart of antiretroviral therapy (rapid ART). SETTING:Prospective open-label randomized controlled trial among PWH-OOC in San Diego, USA. METHODS:PWH-OOC were randomized 1:1 to InstaCare or a time-and-attention control integrating a diet-and-nutrition behavioral intervention also with rapid ART initiation (restart ≤7 days from enrollment). All participants had access to support services (free transport, HIV peer navigation, adherence counseling, and linkage to care) and primary care services (mental health, case management, social work, medication-assisted treatment, and specialist pharmacy). The primary outcomes were viral suppression (<50 copies/mL) and re-engagement with care (≥2 HIV care visits >90 days apart) by 24 weeks. Outcomes were reported on an intention-to-treat basis. RESULTS:Between November 2020 and August 2022, 52 PWH-OOC were enrolled. Baseline substance use in the preceding month (49%), unstable housing (51%), moderate/severe depression (49%), and moderate/severe anxiety (41.7%) were prevalent. Rapid ART was provided for all participants. At week 24, the proportion with HIV viral load <50 copies/mL was 37.3% (19/51) (InstaCare 28.0%, control 46.2%, P = 0.25). Fourteen (27.5%) were engaged with care (InstaCare 7/25 [28.0%], control 7/26 [26.9%], P = 1.00). Most participants (94%) reported low or very low emotional distress associated with rapid ART. Study lost to follow-up by week 24 was high (23/51, 45%). CONCLUSIONS:The InstaCare complex intervention did not improve viral suppression or reengagement with care among PWH-OOC. Investigation of high-intensity, individually adapted interventions is needed among PWH-OOC.

Comprehensive whole genome sequencing (WGS) with hybrid assembly of a multi-drug resistant (MDR) Candida albicans (CA) isolate causing cerebral abscess was performed using Illumina paired end and Oxford Nanopore long read technologies. The innovative technologies utilized here enabled us to resolve fragmented assemblies, and implement comprehensive and detailed genomic analyses involved in antifungal resistance of Candida spp. Functionally important genes (MDR1, CDR2 and SQN2) involved in antifungal resistance were identified and a phylogenetic analysis of the clinical isolate was performed. Additionally, our clinical isolate was found to share 4 single nucleotide polymorphisms with two other sequenced strains of MDR C. auris (381 and 386) including translation elongation factor EF1α and EF3, ATPase activity associated proteins, and the lysine tRNA ligase.

BACKGROUND:While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. METHODS:In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. FINDINGS:Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. INTERPRETATION:Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. FUNDING:National Institutes of Health.

Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID 50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID 50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .

BACKGROUND:The transition between inpatient and outpatient care for hospitalized people with HIV represents an opportunity for linkage and re-engagement in care. We evaluated whether attendance at a post-hospitalization visit ('discharge clinic') within 1-2 weeks of discharge would reduce readmissions and improve retention in care (RIC) among people with HIV in San Diego, California, USA. METHODS:This was a retrospective cohort study of people with HIV hospitalized between June 2020 and November 2021. Our primary outcome was 30-day readmissions among people with HIV who did or did not attend a discharge clinic visit. Secondary outcomes included the effect of discharge clinic attendance on RIC, along with the impact of attendance at any HIV clinic visit within 30 days of discharge on readmissions and RIC. RESULTS:We evaluated 114 people with HIV, of whom 77 (67.5%) and 90 (78.9%) attended a discharge clinic visit or any HIV clinic visit within 30 days of discharge, respectively. Active substance use disorder (SUD) was associated with failing to attend a discharge clinic visit (odds ratio 0.31; 95% confidence interval 0.13-0.77). We observed no significant differences in readmissions between people with HIV who did or did not attend a discharge clinic visit; however, the former had significantly higher 6-month RIC (79.2% vs. 35.1%, p < 0.001). People with HIV attending any HIV clinic visit within 30 days of discharge had significantly fewer 30-day readmissions (8.9% vs. 29.2%, p = 0.02) and better 6-month RIC (75.6% vs. 25%, p < 0.001) than those who did not attend. CONCLUSION:Early hospital follow-up care was associated with a reduction in readmissions among people with HIV. Active SUD was a significant barrier to linkage to outpatient follow-up and RIC.

US regulations mandate annual N95 mask fit testing for healthcare workers, but the optimal testing interval is unknown. In our study using data from 12,565 healthcare workers, the probability of survival free from fit-test failure after 3 years was 99.4%, suggesting that less frequent fit testing every 3 years would be safe.

ABSTRACTThe objective of this study was to determine hospital costs and revenue of universal opt-out HIV ED screening. An electronic medical record (EMR)-directed, automated ED screening program was instituted at an academic medical center in San Diego, California. A base model calculated net income in US dollars for the hospital by comparing annual testing costs with reimbursements using payor mixes and cost variables. To account for differences in payor mixes, testing costs, and reimbursement rates across hospitals in the US, we performed a probabilistic sensitivity analysis. The base model included a total of 12,513 annual 4th generation HIV tests with the following payor mix: 18% Medicare, 9% MediCal, 28% commercial and 8% self-payers, with the remainder being capitated contracts. The base model resulted in a net profit for the hospital. In the probabilistic sensitivity analysis, universal 4th generation HIV screening resulted in a net profit for the hospital in 81.9% of simulations. Universal 4th generation opt-out HIV screening in EDs resulted in a net profit to an academic hospital. Sensitivity analysis indicated that ED HIV screening results in a net-profit for the majority of simulations, with higher proportions of self-payers being the major predictor of a net loss.

Journal Article Reply to Montastruc et al Get access Morgan Birabaharan, Morgan Birabaharan Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, California, USA Correspondence: M. Birabaharan, Division of Infectious Diseases and Global Public Health, University of California, 9500 Gilman Dr, La Jolla, San Diego, CA 92093 (mbirabaharan39@gmail.com). Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas C S Martin, Thomas C S Martin Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, California, USAInfectious Diseases Section, VA Healthcare San Diego, San Diego, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Sanjay R Mehta Sanjay R Mehta Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, California, USAInfectious Diseases Section, VA Healthcare San Diego, San Diego, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 76, Issue 11, 1 June 2023, Page 2045, https://doi.org/10.1093/cid/ciad091 Published: 21 February 2023 Article history Received: 30 January 2023 Editorial decision: 02 February 2023 Published: 21 February 2023 Corrected and typeset: 17 March 2023

Background The benefits of direct-acting antivirals towards the elimination of hepatitis C virus (HCV) in people living with HIV are decreased when individuals are reinfected with HCV following treatment. We aimed to systematically review the existing evidence of HCV reinfection risk after treatment among people living with HIV, including people who inject drugs and men who have sex with men (MSM), and to identify the factors that explain heterogeneity in the incidence of HCV reinfection. Methods For this systematic review and meta-analysis, we searched PubMed, Scopus, Web of Science, Cochrane, PsycINFO, and conference presentations from date of database inception to Jan 10, 2022, for clinical trials and cohort studies providing data that could be used to calculate the incidence of HCV reinfection following HCV treatment. Random-effect meta-analysis models were used to calculate rate estimates. Study-level factors contributing to heterogeneity of reinfection estimates were assessed using meta-regression. This study is registered with PROSPERO, CRD42019146973. Findings 41 studies, predominantly conducted in Europe, were included, with a total of 9024 participants. The incidence of reinfection was 3 center dot 76 cases per 100 person-years of follow-up (95% CI 2 center dot 80-5 center dot 05; I-2 85 center dot 9%) among people living with HIV overall, 6 center dot 01 (4 center dot 54-7 center dot 95; 74 center dot 1%) among MSM, and 3 center dot 29 (2 center dot 01-5 center dot 39; 83 center dot 9%) among people who inject drugs. A similar incidence of reinfection was observed following interferon-based therapy (4 center dot 92 cases per 100 person-years of follow-up, 3 center dot 30-7 center dot 32; I-2 78 center dot 3%) and direct-acting antiviral therapy (3 center dot 88, 2 center dot 51-6 center dot 01; 85 center dot 4%). A higher proportion (>= 85%) of MSM in the study population (adjusted rate ratio 2 center dot 66, 95% CI 1 center dot 37-5 center dot 15) and recent HCV infection (2 center dot 22, 1 center dot 09-4 center dot 55) were associated with an increased incidence of reinfection; a longer duration of follow-up after treatment (0 center dot 97, 0 center dot 96-0 center dot 99) was associated with a decreased incidence. Interpretation Risk of HCV reinfection following treatment in people living with HIV was highest among MSM and those with recent HCV infection. Continued scale-up of HCV treatment and ongoing HCV screening and treatment of infection in this patient population should reduce viraemic burden and risk of reinfection. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved.

Tixagevimab and cilgavimab treatment was associated with higher rates of cardiovascular events in a post hoc analysis of a phase 3 trial. In this large population-based propensity-matched study, we found no increased risk of cardiovascular events up to 90 days after tixagevimab and cilgavimab administration, including in patients with pre-existing cardiovascular disease.