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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.

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.

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.

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.

Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART)-naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection. We compared the NAb activity against autologous and heterologous viruses between 10 participants with intrasubtype B superinfection and 19 monoinfected controls, matched to duration of infection and risk behavior. Three to 6 months after primary infection, individuals who would later become superinfected had significantly weaker NAb activity against tier 1 subtype B viruses (P = 0.003 for SF-162 and P = 0.017 for NL4-3) and marginally against autologous virus (P = 0.054). Lower presuperinfection NAb responses correlated with weaker gp120 binding and lower plasma total IgG titers. Soon after superinfection, the NAb response remained lower, but between 2 and 3 years after primary infection, NAb levels strengthened and reached those of controls. Superinfecting viruses were typically not susceptible to neutralization by presuperinfection plasma. These observations suggest that recently infected individuals with a delayed NAb response against primary infecting and tier 1 subtype B viruses are more susceptible to superinfection.IMPORTANCE Our findings suggest that within the first year after HIV infection, a relatively weak neutralizing antibody response against primary and subtype-specific neutralization-sensitive viruses increases susceptibility to superinfection in the face of repeated exposures. As natural infection progresses, the immune response strengthens significantly in some superinfected individuals. These findings will inform HIV vaccine design by providing testable correlates of protection from initial HIV infection.

ObjectiveThe aim of this study was to characterize the demographic, behavioural, clinical and immunogenetic determinants of HIV-1 superinfection in a high-risk cohort of MSM.DesignA retrospective cohort study of prospectively followed MSM.MethodsNinety-eight MSM with acute or early HIV-1 monoinfection were followed for a median of 15.6 months. Demographic and human leukocyte antigen (HLA) genotype data were collected at enrolment. Sexual behaviour, clinical and the infection status (monoinfection or superinfection) data were recorded at each visit (at enrolment and thereafter at a median of 4.2-month intervals). HIV-1 superinfection risk was determined by Cox regression and Kaplan-Meier survival analysis.ResultsTen individuals (10.2%) had superinfection during follow-up. Cox regression did not show significantly increased superinfection risk for individuals with an increased amount of condomless anal intercourse, lower CD4 T-cell count or higher viral load, but higher number of sexual contacts demonstrated a trend towards significance [hazard ratio, 4.74; 95% confidence interval (95% CI), 0.87-25.97; P = 0.073]. HLA-A*29 (hazard ratio, 4.10; 95% CI, 0.88-14.76; P = 0.069), HLA-B*35 (hazard ratio, 4.64; 95% CI, 1.33-18.17; P = 0.017), HLA-C*04 (hazard ratio, 5.30; 95% CI, 1.51-20.77; P = 0.010), HLA-C*16 (hazard ratio, 4.05; 95% CI, 0.87-14.62; P = 0.071), HLA-DRB1*07 (hazard ratio, 3.29; 95% CI, 0.94-12.90; P = 0.062) and HLA-DRB1*08 (hazard ratio, 15.37; 95% CI, 2.11-79.80; P = 0.011) were associated with an increased risk of superinfection at α = 0.10, whereas HLA-DRB1*11 was associated with decreased superinfection risk (hazard ratio, 0.13; 95% CI, 0.00-1.03; P = 0.054).ConclusionHLA genes may, in part, elucidate the genetic basis of differential superinfection risk, and provide important information for the development of efficient prevention and treatment strategies of HIV-1 superinfection.

ObjectiveCompared with HIV monoinfection, HIV dual infection has been associated with decreased CD4 T-cell counts and increased viral loads. The same markers are also associated with the development of HIV-associated neurocognitive disorder (HAND), which continues to be a prevalent problem in the era of combination antiretroviral therapy (ART). We sought to determine the relationship between dual infection and HAND.MethodsParticipants on ART (N = 38) underwent deep sequencing of four PCR-amplified HIV coding regions derived from peripheral blood mononuclear cell DNA samples. Phylogenetic analyses were performed to evaluate whether two distinct viral lineages, that is, dual infection, were present in the same individual. All study participants underwent neurocognitive, substance use, and neuromedical assessments at each study visit.ResultsOf 38 participants, nine (23.7%) had evidence of dual infection. Using clinical ratings, global neurocognitive impairment was identified in 21 (55%) participants, and multivariate analysis demonstrated a significant association between dual infection and impairment; odds ratio (95% confidence interval) = 18.3 (1.9, 414.2), P = 0.028. Neurocognitive impairment was also associated with lower current (P = 0.028) and nadir (P = 0.043) CD4 T-cell counts.ConclusionsDeep sequencing of HIV DNA populations in blood mononuclear cell identified dual infection in nearly a quarter of HIV-infected adults receiving ART, and dual infection was associated with HAND. Dual infection may contribute to the development of HAND, perhaps because of increased viral diversity. Further investigation is needed to determine how dual infection results in worse neurocognitive performance.

Previous studies reported a relatively low prevalence of transmitted drug resistance (TDR) in South Korea (

To better understand the dynamics of HIV-specific neutralizing antibody (NAb), we examined associations between viral genetic diversity and the NAb response against a multi-subtype panel of heterologous viruses in a well-characterized, therapy-naïve primary infection cohort. Using next generation sequencing (NGS), we computed sequence-based measures of diversity within HIV-1 env, gag and pol, and compared them to NAb breadth and potency as calculated by a neutralization score. Contemporaneous env diversity and the neutralization score were positively correlated (p=0.0033), as were the neutralization score and estimated duration of infection (EDI) (p=0.0038), and env diversity and EDI (p=0.0005). Neither early env diversity nor baseline viral load correlated with future NAb breadth and potency (p>0.05). Taken together, it is unlikely that neutralizing capability in our cohort was conditioned on viral diversity, but rather that env evolution was driven by the level of NAb selective pressure.

BackgroundHuman immunodeficiency virus type 1 (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood. We used ultradeep sequencing (UDS) to estimate the frequency of DI in a primary infection cohort of predominantly men who have sex with men (MSM).Methods HIV-1 genomes from longitudinal blood samples of recently infected, therapy-naive participants were interrogated with UDS. DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis. Coinfection was defined as DI at baseline; superinfection was monoinfection at baseline and DI at a later time point.Results Of 118 participants, 7 were coinfected and 10 acquired superinfection. Superinfection incidence rate was 4.96 per 100 person-years (95% confidence interval [CI], 2.67-9.22); 6 occurred in the first year and 4 in the second. Overall cumulative prevalence of intrasubtype B DI was 14.4% (95% CI, 8.6%-22.1%). Primary HIV-1 incidence was 4.37 per 100 person-years (95% CI, 3.56-5.36).Conclusions Intrasubtype DI was frequent and comparable to primary infection rates among MSM in San Diego; however, superinfection rates declined over time. DI is likely an important component of the HIV epidemic dynamics, and development of stronger immune responses to the initial infection may protect from superinfection.

3D concrete printing (3DCP) requires precise adjustments to parameters to ensure accurate and high-quality prints. However, despite technological advancements, manual intervention still plays a prominent role in this process, leading to errors and inconsistencies in the final printed part. To address this issue, machine learning vision models have been developed and utilized to analyze captured images and videos of the printing process, detecting defects and deviations. The data collected enable automatic adjustments to print settings, improving quality without the need for human intervention. This work first examines various techniques for real-time and offline corrections. It then introduces a specialized computer vision setup designed for real-time control in robotic 3DCP. Our main focus is on a specific aspect of machine learning (ML) within this system, called speed control, which regulates layer width by adjusting the robot motion speed or material flow rate. The proposed framework consists of three main elements: (1) a data acquisition and processing pipeline for extracting printing parameters and constructing a synthetic training dataset, (2) a real-time ML model for parameter optimization, and (3) a depth camera installed on a customized 3D-printed rotary mechanism for close-range monitoring of the printed layer. [ABSTRACT FROM AUTHOR]

Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics in env following superinfection in a limited set of superinfection cases. HIV-1 env pyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination, and viral dynamics were evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to cocirculate. In the final individual, the surviving lineage was the product of interstrain recombination. NAb responses to autologous viruses that were detected within the first 2 years of HIV-1 infection were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in the env coding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination in env between initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers.

HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to four sequential neurocognitive assessments over a median of 160 days (IQR, 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six subjects (8.3 %) had DM at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR, 7.2–12.2). There were 44 (61.1 %) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio, 4.4; 95 % CI, 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier; 95 % CI, 1.0–1.2). This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together, these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.