Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

Sexually Transmitted Infection Prevention Perspectives in Black Men Who Have Sex With Men Taking Preexposure Prophylaxis in New Orleans.

INTRODUCTION: Profound sexual health disparities exist for Black men who have sex with men (MSM) in the US South, including a high prevalence of sexually transmitted infections (STIs). Sexually transmitted infection prevention strategies beyond condoms are needed for Black MSM taking preexposure prophylaxis (PrEP). METHODS: We conducted in-depth interviews with Black MSM taking PrEP in New Orleans, Louisiana. Informed by the Health Belief Model, we asked about participants' perceived susceptibility, severity, and concerns regarding STIs, and perceived benefits of STI prevention. We also asked about willingness to use various STI prevention strategies, including antibiotic prophylaxis. Interviews were audio-recorded and analyzed using applied thematic analysis. RESULTS: We interviewed 24 Black MSM aged 18 to 36 years; half had a recent STI diagnosis. Most participants were concerned about receiving an STI diagnosis, noting shame or disappointment; physical effects were concerning but infrequently considered. Participants described being less likely to use condoms with routine partners or those taking PrEP. Most reported being willing to engage in each of the 6 prevention strategies discussed. CONCLUSIONS: Black MSM taking PrEP voiced concern about STIs, and many noted that they infrequently use condoms. They were willing to engage in methods focused on preventing STIs on an individual or population level.

Development of a Human Immunodeficiency Virus Risk Prediction Model Using Electronic Health Record Data From an Academic Health System in the Southern United States.

BACKGROUND: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is underutilized in the southern United States. Rapid identification of individuals vulnerable to diagnosis of HIV using electronic health record (EHR)-based tools may augment PrEP uptake in the region. METHODS: Using machine learning, we developed EHR-based models to predict incident HIV diagnosis as a surrogate for PrEP candidacy. We included patients from a southern medical system with encounters between October 2014 and August 2016, training the model to predict incident HIV diagnosis between September 2016 and August 2018. We obtained 74 EHR variables as potential predictors. We compared Extreme Gradient Boosting (XGBoost) versus least absolute shrinkage selection operator (LASSO) logistic regression models, and assessed performance, overall and among women, using area under the receiver operating characteristic curve (AUROC) and area under precision recall curve (AUPRC). RESULTS: Of 998 787 eligible patients, 162 had an incident HIV diagnosis, of whom 49 were women. The XGBoost model outperformed the LASSO model for the total cohort, achieving an AUROC of 0.89 and AUPRC of 0.01. The female-only cohort XGBoost model resulted in an AUROC of 0.78 and AUPRC of 0.00025. The most predictive variables for the overall cohort were race, sex, and male partner. The strongest positive predictors for the female-only cohort were history of pelvic inflammatory disease, drug use, and tobacco use. CONCLUSIONS: Our machine-learning models were able to effectively predict incident HIV diagnoses including among women. This study establishes feasibility of using these models to identify persons most suitable for PrEP in the South.

Cost-Effectiveness of Long-Acting Injectable HIV Preexposure Prophylaxis in the United States : A Cost-Effectiveness Analysis.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP). OBJECTIVE: To identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States. DESIGN: Simulation, cost-effectiveness analysis. DATA SOURCES: Trial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine-tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed. TARGET POPULATION: 476 700 MSM/TGW at very high risk for HIV (VHR). TIME HORIZON: 10 years. PERSPECTIVE: Health care system. INTERVENTION: CAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP. OUTCOME MEASURES: Primary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP. RESULTS OF BASE-CASE ANALYSIS: Compared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price <$4100 per year). RESULTS OF SENSITIVITY ANALYSIS: In a PrEP-eligible population at high risk for HIV, rather than at VHR (n = 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most $100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year). LIMITATION: Uncertain clinical and economic benefits of averting future transmissions. CONCLUSION: Effective oral PrEP limits the additional price society should be willing to pay for CAB-LA. PRIMARY FUNDING SOURCE: FHI 360; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; the Reich HIV Scholar Award; and the Steve and Deborah Gorlin MGH Research Scholars Award.

Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial.

Importance: Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. Objective: To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. Design, Setting, and Participants: Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. Interventions: Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587). Main Outcomes and Measures: The primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. Results: The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%; odds ratio, 0.43 [95% CI, 0.28-0.68]; P < .001; absolute risk difference, -6.6 [95% CI, -10.7 to -2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). Conclusions and Relevance: Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT04497987.

Minimal Impact of Implemented Early Warning Score and Best Practice Alert for Patient Deterioration.

OBJECTIVES: Previous studies have looked at National Early Warning Score performance in predicting in-hospital deterioration and death, but data are lacking with respect to patient outcomes following implementation of National Early Warning Score. We sought to determine the effectiveness of National Early Warning Score implementation on predicting and preventing patient deterioration in a clinical setting. DESIGN: Retrospective cohort study. SETTING: Tertiary care academic facility and a community hospital. PATIENTS: Patients 18 years old or older hospitalized from March 1, 2014, to February 28, 2015, during preimplementation of National Early Warning Score to August 1, 2015, to July 31, 2016, after National Early Warning Score was implemented. INTERVENTIONS: Implementation of National Early Warning Score within the electronic health record and associated best practice alert. MEASUREMENTS AND MAIN RESULTS: In this study of 85,322 patients (42,402 patients pre-National Early Warning Score and 42,920 patients post-National Early Warning Score implementation), the primary outcome of rate of ICU transfer or death did not change after National Early Warning Score implementation, with adjusted hazard ratio of 0.94 (0.84-1.05) and 0.90 (0.77-1.05) at our academic and community hospital, respectively. In total, 175,357 best practice advisories fired during the study period, with the best practice advisory performing better at the community hospital than the academic at predicting an event within 12 hours 7.4% versus 2.2% of the time, respectively. Retraining National Early Warning Score with newly generated hospital-specific coefficients improved model performance. CONCLUSIONS: At both our academic and community hospital, National Early Warning Score had poor performance characteristics and was generally ignored by frontline nursing staff. As a result, National Early Warning Score implementation had no appreciable impact on defined clinical outcomes. Refitting of the model using site-specific data improved performance and supports validating predictive models on local data.

Determinants of Left Ventricular Hypertrophy and Diastolic Dysfunction in an HIV Clinical Cohort.

OBJECTIVE: The aim of this work was to investigate determinants of structural myocardial abnormalities in persons living with human immunodeficiency virus (PLWH). METHODS AND RESULTS: We reviewed archived transthoracic echocardiograms (TTEs) performed on PLWH at Duke University Medical Center from 2001 to 2012. The primary outcomes were presence of left ventricular hypertrophy (LVH) or diastolic dysfunction (DD). TTEs for 498 human immunodeficiency virus-infected persons were reviewed (median age 44 years, 38% female, 72% black, 34% with hypertension, 15% with diabetes). Among those with usable images, LVH was detected in 174 of 473 persons (37%) according to LV mass criteria and in 99 of 322 persons (31%) according to American Society of Echocardiography LV mass index criteria. Definite DD was detected in 18 of 224 persons (8%). LVH was more common in PLWH with a CD4 count ≤ 200 cells/mm3 proximal to TTE (adjusted OR 1.68, 95% CI 1.08-2.62), CD4 nadir ≤ 200 cells/mm3 (adjusted OR 1.63, 95% CI 1.04-2.54) and less common in persons with viral suppression (OR 0.46, 95% CI 0.27-0.80). Lower CD4 nadirs (P = .002) and proximal CD4 counts (P = .002) were also associated with DD. CONCLUSIONS: Persons with a history of advanced human immunodeficiency virus-associated immune suppression are at higher risk of LVH and DD than infected persons with preserved immune function.

Metabolites predict cardiovascular disease events in persons living with HIV: a pilot case-control study.

Introduction: Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking. Methods: Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis. Results: Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p = 0.08) and glutamine/valine (p = 0.003) were elevated in CAD cases compared to controls. Conclusion: SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.

An educational initiative in response to identified PrEP prescribing needs among PCPs in the Southern U.S.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but many primary care physicians (PCPs) have not incorporated PrEP into practice. While PrEP may be a key strategy to reducing high HIV transmission rates in the southern US, knowledge about PrEP prescribing patterns among PCPs in this region is lacking. An online survey was sent to a large network of PCPs at an academic medical center in North Carolina in October 2015. The survey was repeated in September 2016, after an educational intervention that included on-site trainings at 14 PCP offices. Chi-square tests were used to compare PrEP prescribing patterns among providers. The initial survey was sent to 389 PCPs, with 115 (30%) responding. Of these, 78% reported seeing men who have sex with men (MSM). Only 17% had prescribed PrEP. The most frequently identified barrier was lack of knowledge (60%). When the survey was repeated after the educational initiative, 79 PCPs (20%) responded. Of these, 90% reported seeing MSM, and 35% had prescribed PrEP. PCPs who had attended a training were more likely to have prescribed PrEP (OR 4.84, CI 1.77-13.21). In conclusion, PrEP prescribing among PCPs in the southern US is low. A survey among PCPs identified lack of knowledge as a barrier to prescribing, motivating an institutional-wide educational campaign in response. Further efforts are needed to continue to raise awareness and educate PCPs in the South about PrEP.

Screening Veterans for Syphilis: Implementation of the Reverse Sequence Algorithm.

We evaluated the syphilis reverse sequence algorithm (RSA) in a Veteran Affairs facility, finding 5.5% reactive Treponema pallidum enzyme immunoassay (EIA) tests. In a subset of EIA+/VDRL-/TP-PA+ cases, 48% were previously treated. Of veterans with unknown/no prior therapy, only 45% had documentation of subsequent treatment, suggesting suboptimal interpretation of RSA results.

Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. METHODS: We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40-75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. RESULTS: Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). CONCLUSIONS: Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations.

Treatment of syphilis: a systematic review.

IMPORTANCE: The incidence of syphilis in the United States is increasing; it is estimated that more than 55,000 new infections will occur in 2014. Treatment regimens are controversial, especially in specific populations, and assessing treatment response based on serology remains a challenge. OBJECTIVE: To review evidence regarding penicillin and nonpenicillin regimens, implications of the "serofast state," and treatment of specific populations including those with neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women. EVIDENCE REVIEW: We searched MEDLINE for English-language human treatment studies dating from January 1965 until July 2014. The American Heart Association classification system was used to rate quality of evidence. FINDINGS: We included 102 articles in our review, consisting of randomized trials, meta-analyses, and cohort studies. Case reports and small series were excluded unless they were the only studies providing evidence for a specific treatment strategy. We included 11 randomized trials. Evidence regarding penicillin and nonpenicillin regimens was reviewed from studies involving 11,102 patients. Data on the treatment of early syphilis support the use of a single intramuscular injection of 2.4 million U of benzathine penicillin G, with studies reporting 90% to 100% treatment success rates. The value of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals. Less evidence is available regarding therapy for late and late latent syphilis. Following treatment, nontreponemal serologic titers should decline in a stable pattern, but a significant proportion of patients may remain seropositive (the "serofast state"). Serologic response to treatment should be evident by 6 months in early syphilis but is generally slower (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy. CONCLUSIONS AND RELEVANCE: The mainstay of syphilis treatment is parenteral penicillin G despite the relatively modest clinical trial data that support its use.

Client Perspectives on the Development of a Rapid PrEP Initiative at a Sexual Health Center in New Orleans, Louisiana.

Uptake of PrEP remains suboptimal, especially in the Southern United States. Same-day or "Rapid PrEP Initiatives" (RPIs) in sexual health centers (SHCs) could facilitate access and overcome barriers to PrEP. We studied the adaptation of an RPI from Denver, Colorado to an SHC in New Orleans, Louisiana. Through focus group discussions (FGDs) with local SHC staff and PrEP providers, we developed a preliminary RPI model. In 5 FGDs with SHC clients referred for or taking PrEP, we gathered adaptation recommendations and feedback on model acceptability, feasibility, and utility. Providers and clients voiced unanimous support for the RPI. Clients favored the ease of same-day PrEP initiation and emphasized a desire for navigational support, financial counseling, and integration of PrEP care with their other clinical needs. Clients recommended that SHC providers discuss PrEP and HIV with all patients, regardless of providers' perception of risk. Next steps include small-scale implementation and evaluation.

Client Perspectives on the Development of a Same-Day PrEP Initiation Protocol at a Sexual Health Center in New Orleans, LouisianaUptake of PrEP remains low, especially in the Southern United States. Same-day or "Rapid PrEP Initiatives" (RPIs) in sexual health centers (SHCs) could facilitate access and overcome barriers to PrEP. RPIs provide eligible clients with an opportunity to start PrEP on the same day they receive screening for sexually transmitted infections. We studied the adaptation of an RPI from Denver, Colorado, to an SHC in New Orleans, Louisiana. Through focus group discussions (FGDs) with local SHC staff and PrEP providers, we developed a preliminary RPI model. In five FGDs with SHC clients referred for or taking PrEP, we gathered adaptation recommendations and feedback on RPI model acceptability, feasibility, and utility. Providers and clients voiced unanimous support for the RPI. Clients favored the ease of same-day PrEP initiation and emphasized a desire for navigational support, financial counseling, and integration of PrEP care with their other clinical needs. Clients recommended that SHC providers discuss PrEP and HIV with all patients, regardless of providers' perception of risk. Next steps include small-scale implementation and evaluation.

Identifying Implementation Strategies to Enhance HIV Pre-Exposure Prophylaxis Uptake Among Black Cisgender Women in New Orleans, Louisiana.

There is an unmet need for HIV prevention among Black cisgender women. From January to November 2020, we conducted formative research to develop locally informed implementation strategies to enhance pre-exposure prophylaxis (PrEP) uptake among Black cisgender women in New Orleans, Louisiana. Following an iterative process, we conducted in-depth interviews (IDIs) with Black women who were not taking PrEP and used those findings to inform IDIs with Black women taking PrEP. We asked about PrEP awareness, social support, PrEP-related norms, medical mistrust, motivation to take PrEP, and potential implementation strategies. Data were analyzed using applied thematic analysis. We established the Black Women and PrEP (BWAP) Task Force-a diverse group of 25 Black female community representatives who reviewed the IDI findings and identified strategies to address these determinants of PrEP uptake. We interviewed 12 Black women who were not taking PrEP and 13 Black women who were taking PrEP. Two main PrEP uptake barriers were identified from the IDI findings and Task Force discussions. First, Black women do not know of other Black women taking PrEP. Women perceived PrEP as a drug for gay men. Most said that testimonials from Black women taking PrEP would make its use more relatable. Second, Black women are not frequently offered PrEP by their providers. Many preferred accessing PrEP through women's health providers. The Task Force identified two strategies to address these barriers: a social media campaign for women and an educational initiative to train providers to discuss and prescribe PrEP. These implementation strategies require further study.

Characteristics of Mpox Infections in Louisiana in the 2022 Outbreak.

The 2022 outbreak of mpox in Louisiana was limited to just >300 cases, perhaps an unexpected outcome given the state's high rates of HIV and other sexually transmitted infections (STIs). We aimed to describe the local outbreak within two health centers in the New Orleans region, partnering with the Louisiana Department of Health to offer additional statewide data. We reviewed charts of persons testing positive for mpox in New Orleans from July to November 2022 at two local health centers that together accounted for half of local cases. We abstracted data on HIV status, immune function [CD4 count, viral load (VL)], antiretroviral therapy regimen, symptoms and severity of infection, vaccination status, and whether tecovirimat was administered. We present local data relative to statewide data (July 2022-January 2023). Of 103 individuals in our network for whom charts were reviewed, 96 (93%) identified as male, 52 (50%) were Black, and 69 (67%) had HIV, including 12 (17%) with uncontrolled HIV (CD4 < 200 cells/mm3 or VL >200 copies/mL). The most common presenting symptoms were rash (n = 71, 69%), fever (n = 36, 35%), and rectal pain (n = 33, 32%). Of six (6%) patients hospitalized, four (67%) were persons with HIV (PWH). Two were hospitalized for severe mpox infection with >100 lesions at presentation; both were PWH, and one had uncontrolled infection. Across the state, 307 cases have been identified and 24 have been hospitalized. Of those hospitalized, 18 (75%) were PWH, including 9 (50%) with uncontrolled HIV. The demographic data from Louisiana, a state with high prevalence of STIs and HIV/AIDS, are consistent with prior reports describing the 2022 mpox outbreak. Our results contribute to accumulating data on the severity of infection in individuals with HIV-related immunocompromise.

A Multicomponent Intervention to Train and Support Family Medicine Providers to Promote Pre-exposure Prophylaxis (PrEP) for Adolescent Girls and Young Women in the Deep South: Protocol for the PrEP-Pro Study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective biomedical prevention intervention and a major strategy for reducing the HIV burden in the United States. However, PrEP provision and uptake remain lower than estimated needs, and in ways that may exacerbate HIV disparities among Black adolescent girls and young women in the southern United States. Data suggest that gaps in provider knowledge of HIV epidemiology and PrEP and skills assessing sexual health practices are important barriers to provision and uptake, with limited evidence-based interventions to address these gaps. OBJECTIVE: This paper describes the "PrEP-Pro" intervention, a multicomponent intervention to train and support family medicine (FM) trainees to promote PrEP for adolescent girls and young women in Alabama. METHODS: The PrEP-Pro intervention comprises 3 main components guided by the Capability-Opportunity-Motivation-Behavior (COM-B) model for behavioral change and the Consolidated Framework for Implementation Research (CFIR): (1) provider HIV epidemiology and PrEP education, (2) sexual history taking, and (3) PrEP Champions. In phase 1, we will work with community advisory boards (providers and clients) and then conduct focus groups with FM trainees to adapt content to train FM residents on HIV epidemiology and PrEP and develop implementation strategies, including provider-facing tools and client-facing educational materials. In phase 2, we will pretest and then pilot-test the initially adapted PrEP-Pro intervention with FM trainees. FM trainees will complete baseline, 3-, and 6-month questionnaires post PrEP-Pro intervention. We will also conduct in-depth interviews (IDIs) with FM pilot participants, adolescent girls and young women who accessed care after the PrEP-Pro pilot, and key stakeholders. The primary outcomes are PrEP-Pro acceptability and feasibility, which would be assessed using validated instruments at months 3 (among pretest participants) and 6 (among pilot participants). Secondary outcomes will also be assessed, including PrEP knowledge, sexual history-taking attitudes and practices, PrEP prescriptions among adolescent girls and young women encounters, and sexually transmitted infections (STIs) and HIV testing among adolescent girls and young women encounters in 6 months. RESULTS: Study results will be disseminated to practices, state health officials, and other key stakeholders to solicit feedback on implementation opportunities and challenges to inform a hybrid effectiveness implementation trial. Our results will also be presented at local and national conferences and submitted to peer-reviewed journals. CONCLUSIONS: As PrEP grows, there is a pressing need to train FM providers and develop appropriate, contextually relevant tools to support PrEP implementation. The PrEP-Pro intervention is a multicomponent intervention to train FM residents across Alabama on sexual history-taking, PrEP provision for adolescent girls and young women, and supporting practice-based PrEP Champions. The PrEP-Pro intervention is anticipated to increase PrEP prescriptions for adolescent girls and young women and expand comprehensive sexual and reproductive health care for adolescent girls and young women in rural and urban Alabama. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44908.

Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial.

BACKGROUND: Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study. METHODS: The HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094. FINDINGS: Of the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation. INTERPRETATION: Long-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance. FUNDING: Division of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.

HIV Prevention During the COVID-19 Pandemic: Sexual Activity and PrEP Use Among Black Same-Gender-Loving Men and Black Cisgender Women.

Black populations in the U.S. South are disproportionally affected by HIV and COVID-19 due to longstanding inequalities. We conducted 20 in-depth interviews-12 with Black same-gender-loving men and 8 with Black cisgender women-to explore the impact of the initial phase of the COVID-19 pandemic on sexual activities and PrEP use. Almost all participants reduced the frequency of sex and number of partners. Women described little interest in sex, whereas men began to connect with some sexual partners after stay-at-home orders were lifted. Both populations were concerned about contracting COVID-19 through sexual partners, and men described selecting partners based on perceived COVID-19 risk. Participants valued PrEP and could access it, although several men who were not having sex stopped taking it. Risk of acquiring HIV during this time was likely limited. Future qualitative research is needed to understand how sexual behaviors and PrEP use changed as the pandemic continued.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.

Background: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. Methods: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Results: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.