Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. CONCLUSIONS: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).

Relative Cost and Infectious Days Averted Associated With Rapid Gonorrhea and Chlamydia Testing Among Men Who Have Sex With Men.

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.

Prioritization of ethical concerns regarding HIV molecular epidemiology by public health practitioners and researchers.

BACKGROUND: HIV molecular epidemiology (HIV ME) can support the early detection of emerging clusters of new HIV infections by combining HIV sequence data routinely obtained during the clinical treatment of people living with HIV with behavioral, geographic, and sociodemographic information. While information about emerging clusters promises to facilitate HIV prevention and treatment efforts, the use of this data also raises several ethical concerns. We sought to assess how those working on the frontlines of HIV ME, specifically public health practitioners (PHPs) and researchers, prioritized these issues. METHODS: Ethical issues were identified through literature review, qualitative in-depth interviews, and stakeholder engagement. PHPs and researchers using HIV ME prioritized the issues using best-worst scaling (BWS). A balanced incomplete block design was used to generate 11 choice tasks each consisting of a sub-set of 5 ethical concerns. In each task, respondents were asked to assess the most and least concerning issue. Data were analyzed using conditional logit, with a Swait-Louviere test of poolability. Latent class analysis was then used to explore preference heterogeneity. RESULTS: In total, 57 respondents completed the BWS experiment May-June 2023 with the Swait-Louviere test indicating that researchers and PHPs could be pooled (p = 0.512). Latent class analysis identified two classes, those highlighting "Harms" (n = 29) (prioritizing concerns about potential risk of legal prosecution, individual harm, and group stigma) and those highlighting "Utility" (n = 28) (prioritizing concerns about limited evidence, resource allocation, non-disclosure of data use for HIV ME, and the potential to infer the directionality of HIV transmission). There were no differences in the characteristics of members across classes. CONCLUSIONS: The ethical issues of HIV ME vary in importance among stakeholders, reflecting different perspectives on the potential impact and usefulness of the data. Knowing these differences exist can directly inform the focus of future deliberations about the policies and practices of HIV ME in the United States.

Immunogenicity of a 2-Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.

Immunogenicity of the BA.1 and BA.4/BA.5 Severe Acute Respiratory Syndrome Coronavirus 2 Bivalent Boosts: Preliminary Results From the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Association between where men who have sex with men (MSM) meet sexual partners and chlamydia/gonorrhoea infection before and during the COVID-19 pandemic in San Diego, California.

BACKGROUND: Meeting sex partners online is associated with increased risk of acquiring sexually transmitted infections. We examined whether different venues where men who have sex with men (MSM) meet sex partners was associated with prevalent Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, and whether prevalence increased during (vs before) the COVID-19 pandemic. METHODS: We conducted a cross-sectional analysis of data from San Diego's 'Good To Go' sexual health clinic from two enrolment periods: (1) March-September 2019 (pre-COVID-19) and (2) March-September 2021 (during COVID-19). Participants completed self-administered intake assessments. This analysis included males aged ≥18 years self-reporting sex with males within 3 months before enrolment. Participants were categorised as (1) meeting new sex partners in-person only (eg, bars, clubs), (2) meeting new sex partners online (eg, applications, websites) or (3) having sex only with existing partners. We used multivariable logistic regression, adjusting for year, age, race, ethnicity, number of sex partners, pre-exposure prophylaxis use and drug use to examine whether venue or enrolment period were associated with CT/NG infection (either vs none). RESULTS: Among 2546 participants, mean age was 35.5 (range: 18-79) years, 27.9% were non-white and 37.0% were Hispanic. Overall, CT/NG prevalence was 14.8% and was higher during COVID-19 vs pre-COVID-19 (17.0% vs 13.3%). Participants met sex partners online (56.9%), in-person (16.9%) or only had existing partners (26.2%) in the past 3 months. Compared with having only existing sex partners, meeting partners online was associated with higher CT/NG prevalence (adjusted OR (aOR) 2.32; 95% CI 1.51 to 3.65), while meeting partners in-person was not associated with CT/NG prevalence (aOR 1.59; 95% CI 0.87 to 2.89). Enrolment during COVID-19 was associated with higher CT/NG prevalence compared with pre-COVID-19 (aOR 1.42; 95% CI 1.13 to 1.79). CONCLUSIONS: CT/NG prevalence appeared to increase among MSM during COVID-19, and meeting sex partners online was associated with higher prevalence.

Estimating contact network properties by integrating multiple data sources associated with infectious diseases.

To effectively mitigate the spread of communicable diseases, it is necessary to understand the interactions that enable disease transmission among individuals in a population; we refer to the set of these interactions as a contact network. The structure of the contact network can have profound effects on both the spread of infectious diseases and the effectiveness of control programs. Therefore, understanding the contact network permits more efficient use of resources. Measuring the structure of the network, however, is a challenging problem. We present a Bayesian approach to integrate multiple data sources associated with the transmission of infectious diseases to more precisely and accurately estimate important properties of the contact network. An important aspect of the approach is the use of the congruence class models for networks. We conduct simulation studies modeling pathogens resembling SARS-CoV-2 and HIV to assess the method; subsequently, we apply our approach to HIV data from the University of California San Diego Primary Infection Resource Consortium. Based on simulation studies, we demonstrate that the integration of epidemiological and viral genetic data with risk behavior survey data can lead to large decreases in mean squared error (MSE) in contact network estimates compared to estimates based strictly on risk behavior information. This decrease in MSE is present even in settings where the risk behavior surveys contain measurement error. Through these simulations, we also highlight certain settings where the approach does not improve MSE.

4th Generation HIV screening in the emergency department: net profit or loss for hospitals?

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.

Modeling homophily in dynamic networks with application to HIV molecular surveillance.

BACKGROUND: Efforts to control the HIV epidemic can benefit from knowledge of the relationships between the characteristics of people who have transmitted HIV and those who became infected by them. Investigation of this relationship is facilitated by the use of HIV genetic linkage analyses, which allows inference about possible transmission events among people with HIV infection. Two persons with HIV (PWH) are considered linked if the genetic distance between their HIV sequences is less than a given threshold, which implies proximity in a transmission network. The tendency of pairs of nodes (in our case PWH) that share (or differ in) certain attributes to be linked is denoted homophily. Below, we describe a novel approach to modeling homophily with application to analyses of HIV viral genetic sequences from clinical series of participants followed in San Diego. Over the 22-year period of follow-up, increases in cluster size results from HIV transmissions to new people from those already in the cluster-either directly or through intermediaries. METHODS: Our analytical approach makes use of a logistic model to describe homophily with regard to demographic, clinical, and behavioral characteristics-that is we investigate whether similarities (or differences) between PWH in these characteristics are associated with their sequences being linked. To investigate the performance of our methods, we conducted on a simulation study for which data sets were generated in a way that reproduced the structure of the observed database. RESULTS: Our results demonstrated strong positive homophily associated with hispanic ethnicity, and strong negative homophily, with birth year difference. The second result implies that the larger the difference between the age of a newly-infected PWH and the average age for an available cluster, the lower the odds of a newly infected person joining that cluster. We did not observe homophily associated with prior diagnosis of sexually transmitted diseases. Our simulation studies demonstrated the validity of our approach for modeling homophily, by showing that the estimates it produced matched the specified values of the statistical network generating model. CONCLUSIONS: Our novel methods provide a simple and flexible statistical network-based approach for modeling the growth of viral (or other microbial) genetic clusters from linkage to new infections based on genetic distance.

Lessons learned from the Last Gift study: ethical and practical challenges faced while conducting HIV cure-related research at the end of life.

The Last Gift is an observational HIV cure-related research study conducted with people with HIV at the end of life (EOL) at the University of California San Diego. Participants agree to voluntarily donate blood and other biospecimens while living and their bodies for a rapid research autopsy postmortem to better understand HIV reservoir dynamics throughout the entire body. The Last Gift study was initiated in 2017. Since then, 30 volunteers were enrolled who are either (1) terminally ill with a concomitant condition and have a prognosis of 6 months or less or (2) chronically ill with multiple comorbidities and nearing the EOL.Multiple ethical and logistical challenges have been revealed during this time; here, we share our lessons learnt and ethical analysis. Issues relevant to healthcare research include surrogate informed consent, personal and professional boundaries, challenges posed conducting research in a pandemic, and clinician burnout and emotional support. Issues more specific to EOL and postmortem research include dual roles of clinical care and research teams, communication between research personnel and clinical teams, legally required versus rapid research autopsy, identification of next of kin/loved ones and issues of inclusion. Issues specific to the Last Gift include logistics of body donation and rapid research autopsy, and disposition of the body as a study benefit.We recommend EOL research teams to have clear provisions around surrogate informed consent, rotate personnel to maintain boundaries, limit direct contact with staff associated with clinical care and have a clear plan for legally required versus research autopsies, among other recommendations.

MrHAMER yields highly accurate single molecule viral sequences enabling analysis of intra-host evolution.

Technical challenges remain in the sequencing of RNA viruses due to their high intra-host diversity. This bottleneck is particularly pronounced when interrogating long-range co-evolved genetic interactions given the read-length limitations of next-generation sequencing platforms. This has hampered the direct observation of these genetic interactions that code for protein-protein interfaces with relevance in both drug and vaccine development. Here we overcome these technical limitations by developing a nanopore-based long-range viral sequencing pipeline that yields accurate single molecule sequences of circulating virions from clinical samples. We demonstrate its utility in observing the evolution of individual HIV Gag-Pol genomes in response to antiviral pressure. Our pipeline, called Multi-read Hairpin Mediated Error-correction Reaction (MrHAMER), yields >1000s of viral genomes per sample at 99.9% accuracy, maintains the original proportion of sequenced virions present in a complex mixture, and allows the detection of rare viral genomes with their associated mutations present at <1% frequency. This method facilitates scalable investigation of genetic correlates of resistance to both antiviral therapy and immune pressure and enables the identification of novel host-viral and viral-viral interfaces that can be modulated for therapeutic benefit.

Enumeration of Public Health Nurses in the United States: Limits of Current Standards.

Recent national initiatives in nursing and public health have emphasized the need for a robust public health nursing (PHN) workforce. In this article, we analyze the extent to which recent national enumeration surveys base their counts of this workforce on the definitions, scope, and standards for practice and practice competencies of the PHN nursing specialty. By and large, enumeration surveys continue to rely on practice setting to define the PHN workforce, which is an insufficient approach for meeting the goals of major nursing and public health initiatives. We make recommendations for the development of new standards for PHN enumeration to strengthen the broader public health infrastructure and evaluate PHN contributions to population-level outcomes. (Am J Public Health. 2022;112(S3):S292-S297. https://doi.org/10.2105/AJPH.2022.306782).

Incorporating metadata in HIV transmission network reconstruction: A machine learning feasibility assessment.

HIV molecular epidemiology estimates the transmission patterns from clustering genetically similar viruses. The process involves connecting genetically similar genotyped viral sequences in the network implying epidemiological transmissions. This technique relies on genotype data which is collected only from HIV diagnosed and in-care populations and leaves many persons with HIV (PWH) who have no access to consistent care out of the tracking process. We use machine learning algorithms to learn the non-linear correlation patterns between patient metadata and transmissions between HIV-positive cases. This enables us to expand the transmission network reconstruction beyond the molecular network. We employed multiple commonly used supervised classification algorithms to analyze the San Diego Primary Infection Resource Consortium (PIRC) cohort dataset, consisting of genotypes and nearly 80 additional non-genetic features. First, we trained classification models to determine genetically unrelated individuals from related ones. Our results show that random forest and decision tree achieved over 80% in accuracy, precision, recall, and F1-score by only using a subset of meta-features including age, birth sex, sexual orientation, race, transmission category, estimated date of infection, and first viral load date besides genetic data. Additionally, both algorithms achieved approximately 80% sensitivity and specificity. The Area Under Curve (AUC) is reported 97% and 94% for random forest and decision tree classifiers respectively. Next, we extended the models to identify clusters of similar viral sequences. Support vector machine demonstrated one order of magnitude improvement in accuracy of assigning the sequences to the correct cluster compared to dummy uniform random classifier. These results confirm that metadata carries important information about the dynamics of HIV transmission as embedded in transmission clusters. Hence, novel computational approaches are needed to apply the non-trivial knowledge collected from inter-individual genetic information to metadata from PWH in order to expand the estimated transmissions. We note that feature extraction alone will not be effective in identifying patterns of transmission and will result in random clustering of the data, but its utilization in conjunction with genetic data and the right algorithm can contribute to the expansion of the reconstructed network beyond individuals with genetic data.

A Cross-Sectional Study to Evaluate the Effects of Age and Duration of HIV Infection on Anxiety and Depression in Cisgender Men.

This observational cross-sectional study of 152 people with HIV (PWH) examined the effects of age and estimated duration of HIV infection (EDI) on depressive and anxiety symptoms. All participants were cisgender men and completed the Profile of Moods State (POMS), a self-report inventory of current (i.e., past week) mood states. Overall, study results confirmed higher levels of anxiety and depression in PWH compared to individuals without HIV. Age group (< 50 or ≥ 50 years) moderated the effect of EDI (< 3 or ≥ 3 years) on mood disturbance. Specifically, younger PWH with early diagnosed infection exhibited the highest levels of depression and anxiety, whereas depression and anxiety were attenuated in older PWH with early infection such that their POMS scores did not significantly differ from the HIV-negative and chronically HIV-infected groups. Despite the small sample size and other important limitations in our study design, our preliminary findings confirm previous observations that older people may have some adaptive ability to better handle the acute psychological stressors associated with recent HIV infection.

Coronavirus disease 2019 vaccination is protective of clinical disease in solid organ transplant recipients.

BACKGROUND: Clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in solid organ transplant recipients (SOTRs) is not well documented despite multiple studies demonstrating sub-optimal immunogenicity. METHODS: We reviewed medical records of eligible SOTRs at a single center to assess vaccination status and identify cases of symptomatic COVID-19 from January 1 to August 12, 2021. We developed a Cox proportional hazards model using the date of vaccination and time since transplantation as a time-varying covariate with age and gender as potential time-invariant confounders. Survival curves were created using the parameters estimated from the Cox model. RESULTS: Among 1904 SOTRs, 1362 were fully vaccinated (96% received mRNA vaccines) and 542 were either unvaccinated (n = 470) or partially vaccinated (n = 72). There were 115 cases of COVID-19, of which 12 occurred in fully vaccinated individuals. Cox regression with the date of vaccination and time since transplantation as the time-varying co-variates showed that after baseline adjustment for age and sex, being fully vaccinated had a significantly lower hazard for COVID-19, hazard ratio (HR) = 0.29 and 95% confidence interval ([CI] 0.09, 0.91). CONCLUSION: We found that 2-dose mRNA COVID-19 vaccination was protective of symptomatic COVID-19 in vaccinated versus unvaccinated SOTRs. TWEET: COVID-19 vaccination was associated with a significantly lower hazard for symptomatic COVID-19 (HR 0.29; 95% CI 0.09, 0.91) among 1904 SOT recipients at a single center from January 1 to August 12, 2021.

Ethical and practical considerations for HIV cure-related research at the end-of-life: a qualitative interview and focus group study in the United States.

BACKGROUND: One of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it. METHODS: We conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable. RESULTS: All four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants' comfort and needs at the EOL. CONCLUSION: Because of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research's impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings.

To stay or leave: Public health nurse workforce retention in North Carolina.

States across the country have been experiencing a steady decline in public health nursing workforce, including North Carolina (NC). OBJECTIVES: To better understand retention in the NC Public Health Nurses (PHNs) workforce through an assessment of perceptions of the working environment, stress, intent to stay, and job satisfaction. DESIGN: A cross-sectional online survey using closed and open-ended questions. SAMPLE: The study population comprised of non-supervisory PHNs (n = 672) working at NC local health departments (LHD). MEASUREMENTS: Retention problem, working environment, and job satisfaction measures were adapted from the revised Casey-Fink Registered Nurse Retention Survey© (2009) to fit public health settings. RESULTS: Despite high levels of job satisfaction (79.76%, n = 473), 53% of respondents (n = 323) acknowledged a retention problem within their LHD; 35.32% (n = 203) planned to/considered leaving their position in the next 3 years for reasons other than retirement. ANOVAs and Kruskal Wallis Test results showed that those planning to leave had statistically lower scores on perceived working environment and job satisfaction and demonstrated higher negative stress levels. CONCLUSION: Like other states, NC is experiencing a PHN shortages predicted to worsen in coming years. To retain the current workforce, LHDs need to work to improve PHNs working environment, increase PHNs' pay, and alleviate stressors.

Rapid Antiretroviral Therapy Among Individuals With Acute and Early HIV.

HIV transmission is increased during acute and early HIV (AEH). Rapid antiretroviral therapy may shorten the duration of infectivity. We show rapid antiretroviral therapy in AEH is acceptable and effective, with 69.0% of participants starting ART within 7 days of HIV diagnosis disclosure, and 88.1% achieving suppression by 48 weeks.

Effective Human Immunodeficiency Virus Molecular Surveillance Requires Identification of Incident Cases of Infection.

BACKGROUND: Ending the human immunodeficiency virus (HIV) epidemic requires knowledge of key drivers of spread of HIV infection. METHODS: Between 1996 and 2018, 1119 newly and previously diagnosed, therapy-naive persons with HIV (PWH) from San Diego were followed. A genetic distance-based network was inferred using pol sequences, and genetic clusters grew over time through linkage of sequences from newly observed infections. Cox proportional hazards models were used to identify factors associated with the rate of growth. These results were used to predict the impact of a hypothetical intervention targeting PWH with incident infection. Comparison was made to the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic (EHE) molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections. RESULTS: Overall, 219 genetic linkages to incident infections were identified over a median follow-up of 8.8 years. Incident cluster growth was strongly associated with proportion of PWH in the cluster who themselves had incident infection (hazard ratio, 44.09 [95% confidence interval, 17.09-113.78]). The CDC EHE molecular surveillance strategy identified 11 linkages to incident infections a genetic distance threshold of 0.5%, and 24 linkages at 1.5%. CONCLUSIONS: Over the past 2 decades, incident infections drove incident HIV cluster growth in San Diego. The current CDC EHE molecular detection and response strategy would not have identified most transmission events arising from those with incident infection in San Diego. Molecular surveillance that includes detection of incident cases will provide a more effective strategy for EHE.