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BackgroundHIV molecular epidemiology (ME) is the analysis of sequence data together with individual-level clinical, demographic, and behavioral data to understand HIV epidemiology. The use of ME has raised concerns regarding identification of the putative source in direct transmission events. This could result in harm ranging from stigma to criminal prosecution in some jurisdictions. Here we assessed the risks of ME using simulated HIV genetic sequencing data.MethodsWe simulated social networks of men-who-have-sex-with-men, calibrating the simulations to data from San Diego. We used these networks to simulate consensus and next-generation sequence (NGS) data to evaluate the risks of identifying direct transmissions using different HIV sequence lengths, and population sampling depths. To identify the source of transmissions, we calculated infector probability and used phyloscanner software for the analysis of consensus and NGS data, respectively.ResultsConsensus sequence analyses showed that the risk of correctly inferring the source (direct transmission) within identified transmission pairs was very small and independent of sampling depth. Alternatively, NGS analyses showed that identification of the source of a transmission was very accurate, but only for 6.5% of inferred pairs. False positive transmissions were also observed, where one or more unobserved intermediaries were present when compared to the true network.ConclusionSource attribution using consensus sequences rarely infers direct transmission pairs with high confidence but is still useful for population studies. In contrast, source attribution using NGS data was much more accurate in identifying direct transmission pairs, but for only a small percentage of transmission pairs analyzed.

IntroductionThe Last Gift study at the University of California San Diego (UCSD), United States enrolls terminally ill people with HIV (PWH) in HIV cure research.MethodsFrom 2017 to 2022, we conducted surveys with Last Gift participants and their next-of-kin/loved ones to evaluate willingness to participate in different types of HIV cure research at the end of life (EOL). We analyzed willingness data descriptively.ResultsWe surveyed 17 Last Gift participants and 17 next-of-kin/loved ones. More than half of Last Gift participants ( n  = 10; 58.8%) expressed willingness to participate in studies involving totally new treatments or approaches ('first-in-human' studies), a combination of different approaches, the use of unique antibodies, proteins or molecules, or therapeutic vaccines. Under one-quarter of Last Gift participants ( n  = 4; 23.5%) expressed willingness to participate in research involving interventions that may shorten their life expectancy to benefit medical research. Most Last Gift participants and their next-of-kin/loved ones also expressed high acceptance for various types of donations and biopsies at the EOL (e.g. hair donations and skin, lymph node or gut biopsies).DiscussionKnowing whether people would be willing to participate in different types of EOL HIV cure research can help inform the design of future innovative studies. As a research community, we have a duty to design studies with adequate safeguards to preserve the public trust in research and honor PWH's important gift to humanity.

BackgroundHIV 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.MethodsEthical 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.ResultsIn 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.ConclusionsThe 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.

BackgroundMeeting 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.MethodsWe 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).ResultsAmong 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).ConclusionsCT/NG prevalence appeared to increase among MSM during COVID-19, and meeting sex partners online was associated with higher prevalence.

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.

BackgroundAccurate estimates of HIV incidence are necessary to monitor progress towards Ending the HIV Epidemic (EHE) initiative targets (90% decline by 2030). U.S. incidence estimates are derived from a CD4 depletion model (CD4 model). We performed simulation-based analyses to investigate the ability of this model to estimate HIV incidence when implementing EHE interventions that have the potential to shorten the duration between HIV infection and diagnosis (diagnosis delay).MethodsOur simulation study evaluates the impact of three parameters on the accuracy of incidence estimates derived from the CD4 model: rate of HIV incidence decline, length of diagnosis delay, and sensitivity of using CD4 + cell counts to identify new infections (recency error). We model HIV incidence and diagnoses after the implementation of a theoretical prevention intervention and compare HIV incidence estimates derived from the CD4 model to simulated incidence.ResultsTheoretical interventions that shortened the diagnosis delay (10-50%) result in overestimation of HIV incidence by the CD4 model (10-92%) in the first year and by more than 10% for the first 6 years after implementation of the intervention. Changes in the rate of HIV incidence decline and the presence of recency error had minimal impact on the accuracy of incidence estimates derived from the CD4 model.ConclusionIn the setting of EHE interventions to identify persons with HIV earlier during infection, the CD4 model overestimates HIV incidence. Alternative methods to estimate incidence based on objective measures of incidence are needed to assess and monitor EHE interventions.

IntroductionAlthough current antiretroviral therapy allows most people with HIV (PWH) to experience normal longevity with a good quality of life, an HIV cure remains elusive due to HIV reservoir formation within deep tissues. An HIV cure remains highly desirable to the community of PWH. This study reports on the perceived risks and benefits of participation in the Last Gift study, a study aimed at characterizing HIV reservoirs via post-mortem autopsy, among PWH at the end of life (EOL) and their next-of-kin (NOK)/loved ones.MethodsLast Gift participants (PWH with a terminal illness and/or near the end of life) and their NOK/loved ones were surveyed for perceptions of risks, benefits, and meaning for participation in the Last Gift study.ResultsThe average age of the 17 Last Gift participants was 66.6 years, 3 were females, 1 person identified as Hispanic, and 15 as Caucasian. The average age of the 17 NOK/loved ones was 56.7 years, and relationships to Last Gift participants included partner/spouse, sibling, friend, child, parent, grandparent, and nephew. The only perceived personal risk of the Last Gift among participants was the blood draws (3/17). NOK/loved ones perceived the following risks: blood draws (2/17), physical pain (3/17), worry that something bad will happen (2/17), and unpleasant side effects (1/17). Participants in Last Gift and NOK/loved ones indicated the study had various positive social effects. For both participants and NOK/loved ones, the most frequent perceived personal benefit of the Last Gift was the satisfaction of supporting HIV cure research.DiscussionParticipants perceived minimal personal and societal risks and valued the altruistic benefits of participating in the Last Gift study. Last Gift participants and NOK/loved ones were cautious about possible personal risks of EOL HIV cure research but still viewed that the emotional, psychological and societal benefits of participation outweighed potential risks.

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.

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.

BackgroundImproved pre-exposure prophylaxis (PrEP) uptake is essential for human immunodeficiency virus (HIV) prevention initiatives. Offering PrEP at the time of HIV and sexually transmitted infection (STI) testing can improve uptake. We offered rapid PrEP initiation in a sexual health clinic and assessed predictors of PrEP interest, initiation, linkage, and retention.MethodsBetween November 2018 and February 2020, PrEP-eligible individuals who presented to a sexual health clinic were offered a free 30-day supply of PrEP plus linkage to continued PrEP care. Univariable and multivariable analyses of demographic and HIV risk data were conducted to determine predictors of PrEP uptake.ResultsOf 1259 adults who were eligible for PrEP (99.7% male, 42.7% White, 36.2% Hispanic), 456 were interested in PrEP, 249 initiated PrEP, 209 were linked, and 67 were retained in care. Predictors of PrEP interest included younger age (P < .01), lower monthly income (P = .01), recreational drug use (P = .02), and a greater number of sexual partners (P < .01). Negative predictors of PrEP initiation included lower monthly income (P = .04), testing positive for chlamydia (P = .04), and exchanging money for sex (P = .01). Negative predictors of linkage included self-identifying as Black (P = .03) and testing positive for an STI (P < .01). Having health insurance positively predicted both linkage (P < .01) and retention (P < .03).ConclusionsA minority of PrEP-eligible HIV and STI testers initiated PrEP when offered, suggesting that easy PrEP access in sexual health clinics alone may not improve uptake. Predictors of uptake included established HIV risk factors and markers of higher socioeconomic status, suggesting that those aware of their risk and with the means to utilize health services engaged best with this model.

• 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.

Initiated in 2017 after extensive community engagement, the Last Gift program enrolls altruistic volunteers willing to donate their cells and tissues at the end of life to allow studies on HIV reservoir dynamics across anatomical sites. As the Last Gift team received tissue requests outside the scope of HIV cure research, we noticed the absence of guiding frameworks to help prioritize the use of altruistically donated human biological materials. In this commentary, we present a proposed framework for prioritizing the use of donated human biological materials within and outside the end-of-life (EOL) HIV cure research context, using the Last Gift study as an example. First, we discuss regulatory and policy considerations, and highlight key ethical values to guide prioritization decisions. Second, we present our prioritization framework and share some of our experiences prioritizing requests for donated human biological materials within and outside EOL HIV cure research.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

BackgroundClinical 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.MethodsWe 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.ResultsAmong 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).ConclusionWe found that 2-dose mRNA COVID-19 vaccination was protective of symptomatic COVID-19 in vaccinated versus unvaccinated SOTRs.TweetCOVID-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.

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 (

BackgroundThe 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.MethodsIn 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.ResultsA 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

Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection. PTC frequency varies greatly based on the definition of a PTC.

BackgroundEvolutionary analyses of well-annotated human immunodeficiency virus (HIV) sequence data can provide insights into viral transmission patterns and associated factors. Here, we explored the transmission dynamics of the HIV-1 subtype B epidemic across the San Diego (US) and Tijuana (Mexico) border region to identify factors that could help guide public health policy.MethodsHIV pol sequences were collected from people with HIV in San Diego County and Tijuana between 1996-2018. A multistep phylogenetic approach was used to characterize the dynamics of spread. The contributions of geospatial factors and HIV risk group to the local dynamics were evaluated.ResultsPhylogeographic analyses of the 2034 sequences revealed an important contribution of local transmission in sustaining the epidemic, as well as a complex viral migration network across the region. Geospatial viral dispersal between San Diego communities occurred predominantly among men who have sex with men, with central San Diego being the main source (34.9%) and recipient (39.5%) of migration events. HIV migration was more frequent from San Diego county towards Tijuana than vice versa. Migrations were best explained by the driving time between locations.ConclusionsThe US-Mexico border may not be a major barrier to the spread of HIV, which may stimulate coordinated transnational intervention approaches. Whereas a focus on central San Diego has the potential to avert most spread, the substantial viral migration independent of central San Diego shows that county-wide efforts will be more effective. Combined, this work shows that epidemiological information gleaned from pathogen genomes can uncover mechanisms that underlie sustained spread and, in turn, can be a building block of public health decision-making.

BackgroundAlthough molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is highly sensitive, the cost can be prohibitive. Those high costs are amplified when the recommended screening approach is used, which requires separate testing of specimens from 3 anatomic sites (rectal, pharyngeal and urogenital). Although individual molecular testing is standard of care, pooled testing may offer a cost-saving alternative.MethodsUsing the Xpert® CT/NG assay (Cepheid, Sunnyvale, CA) we tested urine, rectal and pharyngeal swabs for CT and NG in a high-risk cohort of participants assigned male at birth who reported sex with other persons who were assigned male at birth. Remnant specimens (0.34 mL from each anatomic site) were combined to perform a single 'pooled' test. We calculated positive and negative percent agreement between the pooled testing results with standard of care Xpert CT/NG test results as the reference.ResultsWe conducted 644 pooled tests. Of those, 598 (92.3%) gave CT and NG results. The CT-positive and -negative percent agreement were 90.1% (95% confidence interval [CI], 80.7-95.9%) and 99.2% (98.1-99.8%), respectively. The NG-positive and -negative percent agreement were 96.2% (95% CI, 86.8-99.5%) and 99.8% (95% CI, 99.0-100%), respectively. Pooled testing identified 4 CT and 1 NG infections that were negative at all anatomic sites by individual testing.ConclusionsThree-site pooled CT and NG testing performs similarly to single anatomic site testing among tests providing a valid result. Future cost analyses should evaluate the cost effectiveness of pooled 3-site testing to determine if such a strategy improves the feasibility and accessibility of molecular sexually transmitted infection testing.

GoalWe aimed to assess the incidence rate of coronavirus disease 2019 (COVID-19) in vaccinated versus unvaccinated solid organ transplant recipients (SOTR) at our center.MethodsWe abstracted the following clinical data from our transplant registry from 1/1/2021 to 6/2/2021: demographics, details of COVID-19 vaccination, incidence of COVID-19, and related mortality. We calculated incidence of symptomatic COVID-19 per 1000/person days at risk and incidence rate ratio (IRR).ResultsAmong 2151 SOTRs, 912 were fully vaccinated, and 1239 were controls (1151 unvaccinated, 88 partially vaccinated). Almost 70% of vaccinated subjects received the mRNA-1273 vaccine. There were 65 cases of COVID-19 that occurred during the study period - four occurred among fully vaccinated individuals and 61 among controls (including two in partially vaccinated individuals). Incidence rate for COVID-19 was 0.065 (95% CI 0.024-0.17) per 1000 person days in vaccinated versus 0.34 (95% CI 0.26-0.44) per 1000/person days in the control group; IRR was 0.19 (95% CI 0.049 -0.503, p

BackgroundEnding the HIV epidemic requires knowledge of key drivers of spread of HIV infection.MethodsBetween 1996 and 2018, 1119 newly and previously diagnosed, therapy-naïve 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 CDC EHE molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections.ResultsOverall, 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. (HR 44.09; 95% CI: 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%.ConclusionsOver the past two 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.

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.

BackgroundProphylactic administration of doxycycline is regarded as a potential new public health strategy to combat the rising rates of Chlamydia trachomatis infections and syphilis among men who have sex with men. We conducted a survey-based study to evaluate how community members and health care providers in Southern California would perceive doxycycline preexposure/postexposure prophylaxis (PrEP/PEP) to predict its acceptability and identify potential areas of concern.MethodsWe conducted an online cross-sectional survey among community members who identify as men who have sex with men and health care providers with prescribing authority in Southern California to investigate the current attitudes toward doxycycline PrEP/PEP, including their willingness to accept. We analyzed the data using descriptive statistics and binary logistic regression.ResultsAmong 212 enrolled community member participants, 67.5% indicated they would take doxycycline PrEP/PEP if offered by their provider. Higher acceptability was significantly associated with several characteristics, including recent history of bacterial sexually transmitted infection diagnosis and current use of HIV PrEP. For health care providers, 89.5% of 76 enrolled participants expressed willingness to prescribe doxycycline PrEP/PEP to their patients if recommended by the Centers for Disease Control and Prevention, but only 43.4% were willing if not. Both community members and health care providers demonstrated high levels of concern toward possible drug resistance.ConclusionsDoxycycline PrEP/PEP as a preventive strategy against chlamydial infections and syphilis would likely be accepted among community members and health care providers. Clear guidelines from public health officials and further clarification on the strategy's potential impact on developing drug resistance may be necessary to ensure successful implementation.

The original version of this article unfortunately contained an error, and it has been corrected with this erratum. The original version of this article unfortunately contained and error. “In this article affiliations were incorrect: the affiliation for María J. Marquine should have been “Division of Geriatrics, Gerontology and Palliative Care, University of California, USA”; Sara Gianella, Genevieve Curtin, Susan J. Little, Scott L. Letendre “Department of Medicine, University of California San Diego, 9500 Gilman Drive MC 0679, La Jolla, CA 92093-0679, USA”. The original article has been corrected.

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 (

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

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.

Biometric registration may improve services associated with HIV research. A cross-sectional, observational survey was used to evaluate biometric fingerprint scanning for identification (ID) verification in the setting of an HIV prevention study. Survey outcomes were dichotomized (discouraged or not discouraged) by biometric scanning and statistical analyses were used to determine if participation decreased by greater than 10% overall and after stratifying by demographic variables and risk behaviors. 206 participants were recruited from a community-based HIV and sexual health research screening program. Participants completed a quantitative survey to assess their perceptions of biometric scanning for ID verification. The majority of participants (n = 160; 77.7%) indicated no deterrence from testing due to biometric scanning, yet a significant number (n = 45; 23.3%, P

BackgroundEnding the HIV epidemic requires knowledge of key drivers of spread of HIV infection.MethodsBetween 1996 and 2018, 1119 newly and previously diagnosed, therapy-naïve 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 CDC EHE molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections.ResultsOverall, 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. (HR 44.09; 95% CI: 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%.ConclusionsOver the past two 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.

BackgroundThe predictors of weight gain remain unclear in people with acute and early HIV infection (AEH).MethodsEligible antiretroviral-naïve men diagnosed with AEH from January 1, 2000, to December 31, 2019, were enrolled in an observational cohort study at the University California, San Diego. The study used multivariable mixed-effect linear regression models to analyze differences in the rate of weight gain over time between participants receiving early vs deferred antiretroviral therapy (ART) treatment, low vs high baseline CD4 count and HIV RNA, and different classes of ART.ResultsA total of 463 participants were identified, with mean CD4 cell count of 507 cells/μL and log HIV RNA of 5.0 copies/mL at study entry. There was no difference in the rate of weight gain between participants who did and did not receive ART within 96 weeks of incident HIV infection. Neither a baseline CD4 count of 100 000 copies/mL was a predictor of weight gain. Compared with persons taking non-nucleoside reverse transcriptase inhibitor-based regimens, those who received integrase strand transfer inhibitor (INSTI)-based regimens showed greater weight gain over time.ConclusionsNeither baseline CD4 count and HIV RNA nor early ART was associated with weight change in the first 96 weeks following incident HIV infection. Use of INSTI-based regimens represented a major driver of weight gain in men who initiated ART with relatively higher CD4 cell counts.

In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials, in molecular epidemiology, and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in US-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) legal issues; (4) community engagement; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.

BackgroundTechnology has changed the way that men who have sex with men (MSM) seek sex. More than 60% of MSM in the United States use the internet and/or smartphone-based geospatial networking apps to find sex partners. We correlated use of the most popular app (Grindr) with sexual risk and prevention behavior among MSM.MethodsA nested cohort study was conducted between September 2018 and June 2019 among MSM receiving community-based human immunodeficiency virus (HIV) and sexually transmitted infection (STI) screening in central San Diego. During the testing encounter, participants were surveyed for demographics, substance use, risk behavior (previous 3 months), HIV pre-exposure prophylaxis (PrEP) use, and Grindr usage. Participants who tested negative for HIV and who were not on PrEP were offered immediate PrEP.ResultsThe study included 1256 MSM, 1090 of whom (86.8%) were not taking PrEP. Overall, 580 of 1256 (46%) participants indicated that they used Grindr in the previous 7 days. Grindr users reported significantly higher risk behavior (greater number of male partners and condomless sex) and were more likely to test positive for chlamydia or gonorrhea (8.6% vs 4.7% of nonusers; P = .005). Grindr users were also more likely to be on PrEP (18.7% vs 8.7% of nonusers; P < .001) and had fewer newly diagnosed HIV infections (9 vs 26 among nonusers; P = .014). Grindr users were also nearly twice as likely as nonusers to initiate PrEP (24.6% vs 14%; P < .001).ConclusionsGiven the higher risk behavior and greater acceptance of PrEP among MSM who used Grindr, Grindr may provide a useful platform to promote HIV and STI testing and increase PrEP uptake.

Rapid start of antiretroviral therapy (ART) is quickly becoming best practice around the world. In the US, programs exist to facilitate rapid ART start, but little is known about the experiences of newly diagnosed individuals receiving these recommendations and services. Twenty participants (19 men who have sex with men and 1 transgender woman) from an early ART start program were interviewed to better understand these experiences. Interviews were analyzed for main themes in three general areas: reasons to start, reasons to delay, and factors influencing early ART adherence. Participants reported starting anywhere from right away (same visit as diagnosis) to within a few weeks (median 10.5 days). Reasons to start right away included fear of what could happen if not treated, personal health, influence of people/resources at the clinic, and study participation. Most had small delays in ART start because of structural (insurance, costs) and intentional delays (getting additional medical consultations). Adherence facilitators included desires to improve CD4/viral load and positive beliefs in benefits of suppression. Participants were largely supportive of rapid ART start and appeared to rely on CD4/viral load as "proof" of need for ART, which may be particularly helpful for asymptomatic, newly diagnosed individuals starting ART.

BackgroundTenofovir alafenamide fumarate (TAF) co-formulated with elvitegravir (EVG; E), cobicistat (C), and emtricitabine (F), a recommended antiretroviral regimen, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF) as well as neurocognitive (NC) performance change in participants switching from E/C/F/tenofovir disoproxil fumarate (TDF) to E/C/F/TAF.MethodsThis was a 24-week, single-arm, open-label study in treatment-experienced adults living with human immunodeficiency virus (HIV). Nine participants switched from E/C/F/TDF (150/150/200/300 mg once daily) to E/C/F/TAF (150/150/200/10 mg once daily) at week 12. CSF and total plasma concentrations of EVG, TDF, TAF, tenofovir (TFV), and HIV RNA levels were measured at baseline and week 24. NC performance was estimated by the Montreal Cognitive Assessment.ResultsEVG concentrations in CSF and the CSF:plasma ratio remained stable (P = .203) over time. Following the switch, TFV concentrations in CSF and plasma declined (P = .004), although the TFV CSF:plasma ratio increased (P = .004). At week 24, median TAF plasma concentration was 11.05 ng/mL (range, 2.84-147.1 ng/mL) 2 hours postdose but was below assay sensitivity 6 hours after dosing. TAF was below assay sensitivity in all CSF specimens. HIV RNA was ≤40 copies/mL in all CSF and plasma specimens. Three participants (33%) had NC impairment at baseline and 2 (22%) remained impaired at week 24.ConclusionsSwitch to E/C/F/TAF was associated with reductions in TFV concentrations in CSF but stable EVG concentrations that exceeded the 50% inhibitory concentration for wild-type HIV, suggesting that EVG achieves therapeutic concentrations in the central nervous system. No virologic failure or significant NC changes were detected following the switch.Clinical trials registrationNCT02251236.

BackgroundOnline partner seeking (OPS) among men who have sex with men (MSM) is associated with increased risk behavior including frequency of unprotected anal intercourse, number of partners, and incidence of sexually transmitted infections (STIs). However, the impact on transmission of human immunodeficiency virus (HIV) is uncertain.MethodsMSM diagnosed with acute and early HIV infection were recruited from the Primary Infection Resource Consortium. HIV transmission events in the year following infection were inferred using estimated date of infection combined with genetic network analysis with linked sequences defined as ≤0.015 sequences/site difference in the HIV type 1 (HIV-1) pol coding region. Participants completed a detailed baseline questionnaire including reported methods of meeting sexual partners, including OPS, in the prior 3 months, and regression was performed with inferred transmission as the outcome.ResultsFrom 147 MSM who completed the questionnaire, there were an associated 20 inferred HIV transmissions. No association with OPS was found (odds ratio, 0.64 [95% confidence interval, .24-1.69]; P = .37), though individuals who reported OPS were more likely to have reported a greater number of partners (P = .003) and prior STIs (P = .002). Geospatial analysis did not indicate that OPS was associated with increased geographical reach of the user (P = .68).ConclusionsIndividuals reporting OPS did not have increased odds of inferred HIV-1 transmission in the year following infection using genetic linkage analysis despite apparently increased risk behavior. OPS also did not increase the geographic distance between genetically clustered HIV infections, suggesting that individuals mainly use the internet to meet partners in their local region.

Abstract: Background: Technology has changed the way men-who-have-sex-with-men (MSM) seek sex; ≥60% of MSM in the United States use the internet to find sex partners, primarily via Grindr™ which is the most used dating app among MSM. Studies to date have mostly evaluated Grindr™ use as a dichotomous variable and found inconsistent results regarding associations with increased HIV risk behavior. Importantly, Grindr™ “on-screen” activity is monitored by phones and can provide an objective measure of app usage. Here we aimed to assess Grindr™ “on-screen” activity in MSM undergoing community-based HIV and sexually transmitted infection (STI) screening in San Diego, and to correlate activity with sexual risk behavior and substance use. Methods: This nested cohort study was conducted between December 2018 and April 2019 and leveraged our “Good to Go” (AI106039) screening program for participant recruitment. During their testing encounter participants not on HIV PrEP were provided with surveys on demographics, substance use and risk behavior during previous 3 months, and Grindr™ usage. Participants with iPhones were instructed on how to assess Grindr™ on-screen activity (i.e., time on-screen during last 7 days) on their phones (Figure 1). Risk behavior was classified using the validated San Diego Early Test (SDET) Score (Figure 2). Results: Overall 378/784 (48%) MSM participants indicated that they had opened Grindr™ during the previous 7 days. Grindr™ users had higher SDET scores than those not using Grindr™ (median SDET 2, IQR 0–5; mean 2.29) while there was no difference in proportion of substance users (alcohol and marijuana excluded, 21% vs. 17%; P = 0.14). Of 231 MSM who indicated recent Grindr™ use (61%) had iPhones; median on-screen activity during the previous 7 days was 144 minutes (range 1–2,640 minutes). Participants with high Grindr™ utilization (>80th percentile of time on screen corresponding to >480 minutes), had significantly higher SDET scores (median 5 vs. 2; mean 4.02 vs. 3.26; P < 0.001) and a tendency toward a higher proportion of substance users (29% vs. 20%) than those with lower Grindr™ utilization. Conclusion: This study introduces Grindr™ on-screen activity as an objective measure that can help identify MSM at high risk for HIV. Disclosures: All Authors: No reported Disclosures.

Universal HIV and HCV screening in emergency departments (ED) can reach populations who are less likely to get tested otherwise. The objective of this analysis was to evaluate universal opt-out HIV and HCV screening in two EDs in San Diego. HIV screening for persons aged 13-64 years (excluding persons known to be HIV+ or reporting HIV testing within last 12 months) was implemented using a 4th generation HIV antigen/antibody assay; HCV screening was offered to persons born between 1945 and 1965. Over a period of 16 months, 12,575 individuals were tested for HIV, resulting in 33 (0.26%) new HIV diagnoses, of whom 30 (90%) were successfully linked to care. Universal screening also identified 74 out-of-care for >12-months HIV+ individuals of whom 50 (68%) were successfully relinked to care. Over a one-month period, HCV antibody tests were conducted in 905 individuals with a seropositivity rate of 9.9% (90/905); 61 seropositives who were newly identified or never treated for HCV had HCV RNA testing, of which 31 (51%) resulted positive (3.4% of all participants, including 18 newly identified RNA positives representing 2% of all participants), and 13/31 individuals (42%) were linked to care. The rate of newly diagnosed HCV infections exceeded the rate of newly diagnosed HIV infections by >7-fold, underlining the importance of HCV screening in EDs.

Background: Molecular epidemiology (ME) is a technique used to study the dynamics of pathogen transmission through a population. When used to study HIV infections, ME generates powerful information about how HIV is transmitted, including epidemiologic patterns of linkage and, potentially, transmission direction. Thus, ME raises challenging questions about the most responsible way to protect individual privacy while acquiring and using these data to advance public health and inform HIV intervention strategies. Here, we report on stakeholders' expectations for how researchers and public health agencies might use HIV ME. Methods: We conducted in-depth semistructured interviews with 40 key stakeholders to find out how these individuals respond to the proposed risks and benefits of HIV ME. Transcripts were coded and analyzed using Atlas.ti. Expectations were assessed through analysis of responses to hypothetical scenarios designed to help interviewees think through the implications of this emerging technique in the contexts of research and public health. Results: Our analysis reveals a wide range of imagined responsibilities, capabilities, and trustworthiness of researchers and public health agencies. Specifically, many respondents expect researchers and public health agencies to use HIV ME carefully and maintain transparency about how data will be used. Informed consent was discussed as an important opportunity for notification of privacy risks. Furthermore, some respondents wished that public health agencies were held to the same form of oversight and accountability represented by informed consent in research. Conclusions: To prevent HIV ME from becoming a barrier to testing or a source of public mistrust, the sense of vulnerability expressed by some respondents must be addressed. In research, informed consent is an obvious opportunity for this. Without giving specimen donors a similar opportunity to opt out, public health agencies may find it difficult to adopt HIV ME without deterring testing and treatment.