Challenges recruiting and retaining people at risk for HIV who use methamphetamine in a randomized PrEP adherence trial in Seattle, WA.

BACKGROUND: Methamphetamine is associated with increased HIV risk and suboptimal adherence to pre-exposure prophylaxis (PrEP). Interventions to support PrEP adherence for people who use methamphetamine are needed. METHODS: We evaluated peer navigation to support adherence among people initiating PrEP who use methamphetamine. The HIV Prevention in Methamphetamine Users (HMU!) study enrolled participants from May 2018-January 2022 in Seattle, WA, and followed them for 6 months. Surveys collected sociodemographic, drug use, and sexual behavior data at enrollment, month 3, and month 6. Dried blood spots (DBS) were collected at months 1, 3, and 6 to measure PrEP adherence. RESULTS: We enrolled 21 participants of a target sample of 40, of whom 20 were prescribed PrEP. Nine participants (43%) received peer navigation and 12 (57%) received standard of care or text messaging. At baseline, most participants reported at least weekly methamphetamine use (17, 81%) and condomless receptive anal intercourse (CRAI) (16, 76%). One-third reported CRAI with a partner with HIV. Among those who provided a DBS, 78% and 50% had results commensurate with ≥4 pills/week at the month 3 and 6 visit, respectively. More than half of those prescribed PrEP completed a month 6 visit (11, 55%). Retention was not associated with peer support compared to standard of care or text messaging (p = .20). CONCLUSIONS: We enrolled half our target sample size despite extensive recruitment efforts. As expected, participants had challenges with PrEP adherence and persistence. While peer navigation interventions should be studied further, additional interventions are likely needed to support PrEP uptake, adherence, and persistence among people who use methamphetamine.

Evaluation of cardiovascular effects of intramuscular medetomidine and a medetomidine-vatinoxan combination in Beagle dogs: A randomized blinded crossover laboratory study.

OBJECTIVE: To compare the cardiovascular effects of a combination of medetomidine and vatinoxan (MVX) versus medetomidine (MED) alone administered intramuscularly (IM) and to determine whether heart rate (HR) can be used as a surrogate for cardiac output (CO) after the use of medetomidine with or without vatinoxan. STUDY DESIGN: A randomized, blinded, experimental, crossover study. ANIMALS: A group of eight healthy Beagle dogs aged 4.6 (2.3-9.4) years and weighing 12.9 (9-14.7) kg, median (range). METHODS: Each dog was injected with 1 mg m-2 medetomidine with or without 20 mg m-2 vatinoxan IM with a washout period of 7 days. Cardiovascular data and arterial and mixed venous blood gas samples were collected at baseline, 5, 10, 15, 20, 35, 45, 60, 90 and 120 minutes after treatment administration. CO was measured at all time points via thermodilution. Differences between treatments, period and sequence were evaluated with repeated measures analysis of covariance and the relationship between HR and CO was assessed with a repeated measures analysis of variance; p values < 0.05 were deemed significant. RESULTS: The CO was 47-96% lower after MED than after MVX (p < 0.0001). Increases in systemic, pulmonary arterial and right atrial pressures and oxygen extraction ratio were significantly higher after MED than after MVX (all p < 0.0001). HR was significantly lower after MED and the linear relationship to CO was significant (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Overall, MED affected the cardiovascular system more negatively than MVX, and the difference in cardiovascular function between the treatments can be considered clinically relevant. HR was linearly related to CO, and decreases in HR reflected cardiac performance for dogs sedated with medetomidine with or without vatinoxan.

Seroconversion, seroreversion, and serowaffling among participants initiating antiretroviral therapy in Project DETECT.

BACKGROUND: Incomplete HIV seroconversion and seroreversion are increasingly documented by testing and pre-exposure prophylaxis programs more than previously recognized. This analysis reports on incomplete seroconversion and seroreversion by specimen and test type among Project DETECT participants. METHODS: Project DETECT included a longitudinal study of point-of-care tests. Participants were categorized as having "incomplete seroconversion" if all timepoints had ≥1 nonreactive test at study censoring. Among participants with incomplete seroconversion, we defined "seroreversion" as sustained regression to nonreactive for any test following a reactive result. We define "serowaffling" as any reactive result followed by a nonreactive and then reactive result. We used Fisher's exact tests to explore relationships between Fiebig stage at ART initiation and incomplete seroconversion, seroreversion, and serowaffling. RESULTS: Twenty of 1940 Project DETECT participants met criteria for this subset. Ten participants had complete seroconversion after a median of 23 (IQR 16-47) days following initial positive tests. Ten participants had incomplete seroconversion, eight of whom had seroreversion. Incomplete seroconversion with persistent nonreactive tests was seen only with oral fluid (OF). Of eight participants with seroreversion, all experienced seroreversion of OF tests if the test was ever reactive (n = 6); seroreversion occurred in fingerstick and venipuncture tests in two participants. Serowaffling occurred in nine (45%) participants. No associations were seen between Fiebig stage at ART start and complete seroconversion, seroregression, or serowaffling in our sample. CONCLUSIONS: OF tests may be particularly susceptible to providing false-negative results. Seroreversion and incomplete seroconversion among individuals on antiretroviral treatment may represent a growing problem for HIV testing and treatment programs.

Diagnosis of post-attenuation neurological signs syndrome in a cat with refractory status epilepticus and clinical response to therapeutic plasma exchange.

Case summary: An 8-year-old female spayed British Shorthair cat that underwent surgical portosystemic shunt (PSS) attenuation developed progressive neurological signs 7 days postoperatively. Neurological signs progressed, despite medical management, and seizure activity became rapidly refractory to anticonvulsants. The diagnosis of post-attenuation neurological signs (PANS) was made based on the timing of the occurrence of clinical signs following surgery, absence of hyperammonaemia and suggestive MRI findings of the brain. The cat developed status epilepticus that required treatment with general anaesthesia and mechanical ventilation, from which the cat could not be effectively weaned without the recurrence of seizures. Therapeutic plasma exchange (TPE) was performed as a rescue therapy for PANS and associated refractory status epilepticus. A total of two plasma volumes were processed during one single TPE session. The seizure activity resolved immediately after the TPE session, the cat showed progressive improvement of neurological signs and remained stable thereafter. No significant complications associated with the TPE were observed. The cat was discharged 11 days after admission and was fully recovered. Relevance and novel information: This is an unusual report of PANS diagnosed in a cat based on clinical and MRI findings. The cat developed refractory status epilepticus and had a positive outcome following TPE as rescue therapy. The MRI findings in this report could be useful for the diagnosis of PANS in cats. We speculate that TPE could be taken into consideration as a possible therapeutic intervention in PANS syndrome.

The impact of vatinoxan on microcirculation after intramuscular co-administration with medetomidine in Beagle dogs: a blinded crossover study.

OBJECTIVE: To measure the effects on microcirculation of medetomidine alone (MED) or combined with vatinoxan (MVX). STUDY DESIGN: Randomized, crossover, blinded, experimental study. ANIMALS: A group of eight healthy purpose-bred Beagle dogs. METHODS: Each dog was given 1 mg m-2 MED intramuscularly (IM) or combined with 20 mg m-2 vatinoxan IM (MVX) with a washout period of 7 days. A sidestream dark field (SDF) camera was placed on the buccal mucosa to assess the oral mucosal microcirculation for perfused DeBacker density, proportion of perfused vessels (PPV) (both for all vessels and vessels with a diameter < 20 µm), microvascular flow index (MFI) and heterogeneity index (HI). Videos were recorded at baseline (-5) and 10, 20, 30, 40, 60, 90 and 120 minutes after treatment administration. Linear mixed-effects models were used to assess if microvascular variables were significantly associated with treatment, baseline, and sequence. Results are presented as estimated effect (95% confidence interval), and a p value < 0.05 was considered significant. RESULTS: The interquartile range for baseline measurements was 91.49%-98.42% for PPV, 2.75-3 for MFI and 0-0.36 for HI. Significant effects of treatment and baseline were found. The estimated effect of MED against MVX was -1.98% (-3.53% to -0.42%) for PPV, -0.33 (-0.43 to -0.22) for MFI and 0.14 (0.05 to 0.22) for HI. There were no significant changes seen for perfused DeBacker density, perfused DeBacker density < 20 µm and PPV < 20 µm between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that MVX had significantly fewer effects on buccal mucosal microcirculation than MED. The SDF camera is a useful research tool to assess the microcirculatory status of heavily sedated dogs.

Evaluation of SAMBA II: A Qualitative and Semiquantitative HIV Point-of-Care Nucleic Acid Test.

BACKGROUND: Point-of-care (POC) nucleic acid tests (NATs) have potential to diagnose acute HIV infection and monitor persons taking pre-exposure prophylaxis or antiretroviral therapy (ART). POC NATs have not yet been evaluated in the US. METHODS: From June 2018-March 2019, we conducted a cross-sectional evaluation of the Simple Amplification-Based Assay version II (SAMBA II) POC NAT. People with HIV (PWH) and persons testing for HIV were tested with the SAMBA II qualitative (Qual) whole blood (WB) test. From April-September 2019, the Qual test was used on persons who were ART-naive, and SAMBA II Semi-quantitative (Semi-Q) WB was used with ART-experienced PWH. Both were performed on unprocessed venipuncture (VP) and, when indicated by protocol, fingerstick (FS) WB and plasma. SAMBA results were compared with Abbott RealTime HIV-1 polymerase chain reaction results on plasma. We calculated sensitivity, specificity, and concordance between tests. RESULTS: SAMBA was used in 330 visits among 280 participants: 202 (61.2%) visits from PWH, and 128 (38.8%) from HIV-negative persons. Qual test sensitivity with ART-naive participants was 91.4% [32/35, 95% confidence interval (CI): 77.6% to 97.0%] using VP WB and 100% (27/27, 95% CI: 87.5% to 100%) using FS WB. Specificity was 100% using both specimen types. Concordance between the gold standard and Semi-Q at 1000 copies/mL among PWH on ART was 97.7% (86/88, 95% CI: 92.1% to 99.4%) and 100% (30/30, 95% CI: 88.7% to 100%) using VP and FS WB, respectively. CONCLUSIONS: The SAMBA II POC NATs showed high sensitivity, specificity, and concordance with the gold standard assay, indicating its potential use in diagnostics and monitoring. Future work will evaluate POC NAT implementation in the US.

Prospective Evaluation of HIV Testing Technologies in a Clinical Setting: Protocol for Project DETECT.

BACKGROUND: HIV testing guidelines provided by the Centers for Disease Control and Prevention (CDC) are continually changing to reflect advancements in new testing technology. Evaluation of existing and new point-of-care (POC) HIV tests is crucial to inform testing guidelines and provide information to clinicians and other HIV test providers. Characterizing the performance of POC HIV tests using unprocessed specimens can provide estimates for the window period of detection, or the time from HIV acquisition to test positivity, which allows clinicians and other HIV providers to select the appropriate POC HIV tests for persons who may be recently infected with HIV. OBJECTIVE: This paper describes the protocols and procedures used to evaluate the performance of the newest POC tests and determine their sensitivity during early HIV infection. METHODS: Project DETECT is a CDC-funded study that is evaluating POC HIV test performance. Part 1 is a cross-sectional, retrospective study comparing behavioral characteristics and HIV prevalence of the overall population of the Public Health-Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic to Project DETECT participants enrolled in part 2. Part 2 is a cross-sectional, prospective study evaluating POC HIV tests in real time using unprocessed whole blood and oral fluid specimens. A POC nucleic acid test (NAT) was added to the panel of HIV tests in June 2018. Part 3 is a longitudinal, prospective study evaluating seroconversion sensitivity of POC HIV tests through serial follow-up testing. For comparison, HIV-1 RNA and HIV-1/HIV-2 antigen/antibody tests are also performed for participants enrolled in part 2 or 3. A behavioral survey that collects information about demographics, history of HIV testing, STD history, symptoms of acute HIV infection, substance use, sexual behaviors in the aggregate and with recent partners, and use of pre-exposure prophylaxis and antiretroviral therapy is completed at each part 2 or 3 visit. RESULTS: Between September 2015 and March 2019, there were 14,990 Project DETECT-eligible visits (part 1) to the PHSKC STD Clinic resulting in 1819 part 2 Project DETECT study visits. The longitudinal study within Project DETECT (part 3) enrolled 27 participants with discordant POC test results from their part 2 visit, and 10 (37%) were followed until they had fully seroconverted with concordant positive POC test results. Behavioral survey data and HIV test results, sensitivity, and specificity will be presented elsewhere. CONCLUSIONS: Studies such as Project DETECT are critical for evaluating POC HIV test devices as well as describing characteristics of persons at risk for HIV acquisition in the United States. HIV tests in development, including POC NATs, will provide new opportunities for HIV testing programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/16332.

Performance evaluation of four point-of-care HIV tests using unprocessed specimens.

BACKGROUND: The performance of recently approved point-of-care (POC) HIV tests should be assessed using unprocessed specimens. OBJECTIVE: To evaluate the sensitivity and specificity of four POC HIV tests using whole blood (WB) and two using oral fluid (OF) among persons recruited from health clinics in Seattle, Washington, during September 2015-September 2017. STUDY DESIGN: Participants were tested with the POC tests, additional plasma and serum were collected for laboratory testing, and participant- reported use of antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) was recorded. Participants testing negative on all tests could reenroll every 90 days. Specimens from persons previously diagnosed with HIV infection as well as from those who were newly diagnosed during the study were included in the sensitivity estimate. Sensitivity and specificity were calculated based on HIV status determined by laboratory testing. RESULTS: Of 1,256 visits, 179 were from persons with HIV infection; 120 of these were taking ART. Among 1,077 visits from participants not diagnosed with HIV, PrEP use was reported at 155 (14.4%) visits. Sensitivity was similar among POC WB tests (95.53%-97.21%; p>0.05). Among participants on ART, sensitivity was lower for the same test performed on OF compared to WB (p<0.003). Specificity was high for all tests (99.44%- 100.00%); we did not detect specificity differences with PrEP use. CONCLUSIONS: These POC tests displayed relatively high sensitivity and specificity using unprocessed specimens, suggesting their effectiveness in identifying HIV infections whenever laboratory-based testing is not feasible. Nonetheless, clients with recent risk should retest to rule out the possibility of a false-negative result.

Group Sex Events Among Cisgender Men Who Have Sex With Men: Cross-Sectional and Longitudinal Survey Study to Explore Participation and Risk-Taking Behaviors.

BACKGROUND: Group sex events (GSEs) are common among cisgender men who have sex with men (MSM), pose a unique risk profile for HIV and sexually transmitted disease (STD) transmission, and may be on the rise, in part because of Web-based networking platforms. However, collecting data on GSEs can be challenging, and many gaps exist in our knowledge about GSE participation among MSM. OBJECTIVE: The objective of this study was to develop survey questions addressing aggregate and partner-specific group sex behaviors to measure prevalence of GSEs and associated risks in persons participating in Project Diagnostic Evaluation To Expand Critical Testing Technologies (DETECT), including MSM seeking HIV and STD testing at a public clinic in Seattle, Washington. METHODS: We developed a computer self-assisted survey that included questions about participant demographics, sexual history, and risk behaviors, including group sex, as a part of Project DETECT, a Centers for Disease Control and Prevention-funded study evaluating point-of-care HIV tests. Aggregate and partner-specific questions asked about participation in all GSEs, threesomes, and four-or-more-somes including questions about number and HIV status of sex partners and condom use during the events. To evaluate question performance, we assessed the discrepancies in reporting between the aggregate and partner-specific questions, quantified question refusal rates, and calculated the additional time required to answer the GSE questions. Information about network density (number of partnerships of overlapping duration) was estimated and compared for MSM who did and did not report GSEs. RESULTS: Among 841 visits by 690 MSM who were asked any group sex survey question, participation in a GSE of any type in the past 3 months was reported at 293 visits (293/841, 34.8%). We found that 9.0% (76/841) of MSM in the sample reported ≥1 four-or-more-some in the partner-specific questions but did not report in the aggregate. The proportion of refusals on any given aggregate GSE-related question ranged from 0% (0/273) to 10.6% (15/141) (median 2.6%) and partner-specific questions ranged from 0% (0/143) to 22% (5/23) (median 3.0%), with questions about four-or-more-somes having the highest proportions of refusals. Completing the aggregate group sex questions added 1 to 2 minutes and the partner-specific questions added an additional 2 to 4 minutes per partner to the total survey length. As expected, the partner-specific GSE questions documented higher density of sexual networks that was not captured by asking about total partner counts and overlap of specific partnerships. CONCLUSIONS: We found that the Project DETECT survey was able to obtain nuanced information about GSEs. The question skip patterns and consistency checks were effective, and survey fatigue was minimal. More research is needed on GSEs, and our survey represents a promising data collection tool to help fill gaps in knowledge about the subject.

Draft Genome Sequences of Three Porcine Streptococcus suis Isolates Which Differ in Their Susceptibility to Penicillin.

The draft genome sequences of three Streptococcus suis isolates, IMT40343, IMT40201, and IMT40738, are presented here. These isolates were obtained from bronchoalveolar lavage fluid of healthy and diseased weaners from different German piglet-producing farms and differed in their susceptibility to penicillin.

Plasmid-located dfrA14 gene in Pasteurella multocida isolates from three different pig-producing farms in Germany.

Pasteurella multocida is an important respiratory tract pathogen in intensive livestock farming, especially in pigs. Antimicrobial agents are frequently used to combat infections caused by this pathogen. In a study on antimicrobial resistance among respiratory tract pathogens of pigs from 30 German pig-producing farms, P. multocida isolates (n = 9) with high minimal inhibitory concentration (MIC) values of 16/304 mg/L (n = 2), 32/608 mg/L (n = 3) or ≥64/1216 mg/L (n = 4) for trimethoprim/sulfamethoxazole (1:19) and of ≥512 mg/L (n = 9) for trimethoprim (TMP) were detected in three of these farms. The genetic relatedness of the isolates was investigated via capsule-specific PCR and macrorestriction analyses with ApaI and SmaI. Pulsed-field gel electrophoresis revealed indistinguishable restriction patterns per farm, with slight differences between the three farms. All isolates represented capsular type A. Four representative isolates, that were subjected to whole genome sequencing, shared the multi-locus sequence type (ST) 3. Their plasmids were transformed into E. coli TOP10 with subsequent selection on TMP-containing agar plates. Antimicrobial susceptibility testing and plasmid analysis of the transformants confirmed that they were resistant to sulfonamides and trimethoprim and carried only a single small plasmid. This plasmid was completely sequenced and revealed a size of 6050 bp. Sequence analyses identified the presence of a resistance gene cluster comprising the genes sul2-ΔstrA-dfrA14-ΔstrA-ΔstrB. Further analysis identified a dfrA14 gene cassette being integrated into the strA reading frame. Neither the gene dfrA14 nor this gene cluster have been detected before in P. multocida.

Repeated False-Positive HIV Test Results in a Patient Taking HIV Pre-Exposure Prophylaxis.

Regular HIV testing is required to ensure the safety of HIV pre-exposure prophylaxis (PrEP). We describe and discuss a series of false-positive HIV test results from an individual receiving PrEP. The expansion of PrEP will likely result in greater numbers of false-positive test results that may pose challenges for interpretation.

Antimicrobial susceptibility and genetic relatedness of respiratory tract pathogens in weaner pigs over a 12-month period.

The collaboration project VASIB aims at reducing the antibiotic consumption in pig production by integrating information from consulting expertise in clinical inspection, hygiene, epidemiology, microbiology and pharmacology. In this VASIB subproject, we investigated the antimicrobial susceptibility and relatedness of porcine respiratory tract pathogens. Bordetella bronchiseptica (n = 47), Pasteurella multocida (n = 18) and Streptococcus suis (n = 58) were obtained from weaner pigs at two farms. Antimicrobial susceptibility testing was performed by broth microdilution according to CLSI standards. Resistance genes were detected via specific PCR assays. Macrorestriction analysis was conducted to determine the relatedness of the isolates and to identify clones. The B. bronchiseptica isolates showed indistinguishable (farm 1) or two closely related XbaI-patterns (farm 2). Different SmaI-PFGE patterns of P. multocida isolates were obtained at three different time points. In contrast, PFGE analysis of S. suis indicated more than one fragment pattern per pig and time point. Isolates exhibiting indistinguishable PFGE patterns were considered to represent the same clone. This study showed that only two closely related B. bronchiseptica clones were present in both farms, which had low MICs to all antimicrobials, except to ß-lactams. Different P. multocida clones were present at the three time points. They showed overall low MIC values, with two clones being resistant and one intermediate to tetracycline. S. suis clones were resistant to tetracycline (n = 19) and/or erythromycin/clindamycin (n = 16). They harboured the tetracycline resistance genes tet(O), tet(M) or tet(L) and/or the macrolide/lincosamide/streptogramin B resistance gene erm(B). Five penicillin-resistant S. suis clones were also detected.

"You are always hiding. It's the worst way to live." Exploring Stigma in African Immigrants Living With HIV in a Large Northwest U.S. Metropolitan Area.

African immigrants living in the United States are disproportionately and uniquely affected by HIV. Evidence shows that stigma may contribute to this inequity. Applying a biopsychosocial model of health, our qualitative study explored HIV-related stigma and its impact on African immigrants living with HIV in a large northwestern U.S. metropolitan area. We conducted in-depth, semi-structured interviews with 20 African immigrants living with HIV. In the biological health realm, HIV-related stigma contributed to adverse health care environments, disruptions in care, and poor physical health. In the psychological health realm, it was associated with emotional vulnerability, depressive symptoms, and negative coping. In the social health realm, stigma lead to disclosure challenges, isolation, and poor social support. HIV-related stigma was an extensive and pervasive burden for this population. The biopsychosocial model was a helpful lens through which to explore HIV-related stigma and identify opportunities for future research and intervention.