HIV Risk Perception, Willingness to Use PrEP, and PrEP Uptake Among Young Men who have Sex with Men in Washington, DC.

Low HIV risk perception is a barrier to PrEP uptake, but few studies have examined risk perception and PrEP uptake among young men who have sex with men (YMSM). We performed a secondary analysis of data collected in 2016 from YMSM ages 16-25 in the Washington, DC metropolitan area who participated in a cross-sectional online survey that aimed to identify strategies for engaging YMSM in PrEP services. Of 188 participants, 115 (61%) were considered eligible for PrEP. Among PrEP-eligible participants who had never used PrEP, 53%, 71%, and 100% with low, moderate, and high risk perception, respectively, were willing to use PrEP (Fisher's exact test p = 0.01). Odds of PrEP willingness were greater among those with moderate/high versus low risk perception (adjusted odds ratio [OR] = 5.62, 95% CI = 1.73-18.34). HIV risk perception was not significantly associated with self-reported PrEP use. These findings suggest the importance of risk perception as a correlate of willingness to use PrEP, which is a key step in existing frameworks of PrEP uptake.

Comparison of weight gain after antiretroviral switch to integrase strand transfer inhibitor or tenofovir alafenamide-based therapy.

PURPOSE: Several studies have reported weight gain after switching to integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART). Debate persists if weight gain also occurs when switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF)-based ART. METHODS: We performed a retrospective chart review of virally suppressed HIV-infected patients who were switched from non INSTI- to INSTI-based ART (INSTI switch group) as well as patients switched from TDF- to TAF-based ART (TAF switch group), and compared the mean weight change in these groups to the mean change in weight in patients maintained on NNRTI-based regimens (control group). RESULTS: 329 patients were identified. 256 patients in the INSTI switch group gained a mean 2.4 kg over 17 months compared to 0.5 kg in 54 patients in the control group over the same period (p = 0.008). 161 patients in the TAF switch group gained a mean 2.8 kg over 17 months compared to 0.5 kg in the control group (p = 0.003). There was no statistical difference in weight gain between the INSTI and TAF switch groups. Although the highest mean weight gain of 3.2 kg was seen in those 90 patients switched from both TDF- to TAF-based and non INSTI- to INSTI-based ART (TAF/INSTI switch group), this weight gain was not statistically different compared with the INSTI switch or TAF switch groups. CONCLUSION: Our study suggests that weight gain is associated with both switching HIV regimens from non INSTI- to INSTI-based ART and TDF- to TAF-based ART.

"Knife-cut" intertriginous ulcers related to herpes simplex virus in three patients.

Linear intertriginous erosions and ulcerations related to herpes simplex virus (HSV) infection have been reported in patients with underlying immunosuppression. This rare presentation of HSV seems to occur predominantly in patients undergoing treatment of hematologic malignancies and rheumatologic conditions. Herein, we report three cases of linear "knife-cut" ulcerations in patients who were not undergoing active pharmacologic immunosuppressive therapy and lacked coexisting malignancy or autoimmune disease. Close examination of the skin folds for HSV infection is warranted to rule out disseminated infection as early intervention can be lifesaving.

Acceptability of Long-Acting Injectable Cabotegravir (CAB LA) in HIV-Uninfected Individuals: HPTN 077.

Long-acting injectable PrEP could offer an alternative to daily oral PrEP, improve adherence and protection, if found acceptable, safe and effective. HPTN 077 evaluated injectable cabotegravir safety, tolerability and pharmacokinetics among HIV-uninfected males and females in sequentially-enrolled cohorts of two dosing strategies. We compared acceptability of product attributes, prevention preferences and future interest in injectable PrEP (FIIP) by region, sex-at-birth, arm and cohort and used multivariable analysis to identify FIIP determinants. Baseline injectable PrEP preferences were higher in non-U.S. sites and increased in both regions over time. In multivariable models, FIIP was most strongly associated with acceptability of product attributes, was higher in non-U.S. sites and more altruistic participants. Treatment arm and report of pain were not associated with FIIP. Injectable acceptability was highest in non-U.S. sites. Preferences for injectable versus other PrEP methods were higher among U.S. males than females, but higher among males and females in non-U.S. settings.

Use of BioFire FilmArray gastrointestinal PCR panel associated with reductions in antibiotic use, time to optimal antibiotics, and length of stay.

BACKGROUND: Rapid and accurate diagnostic tools are needed for appropriate management of infectious diarrhea. METHODS: We evaluated the impact of the introduction of rapid multiplex PCR testing using the FilmArray gastrointestinal (GI) panel (BioFire Diagnostics, LLC, Salt Lake City, UT) at our institution, and compared the results to those of standard stool cultures. RESULTS: The most common pathogens detected by the FilmArray GI panel were Clostridium difficile (55.0%), Campylobacter species (20.9%), Salmonella species (12.4%), and Shigella/EIEC species (12.4%). Rates of reproducibility in stool culture for these pathogens ranged from 56.3 to 77.8%. Co-detection of two or more organisms was common (24.2%), most commonly involving EPEC, EAEC, ETEC, and STEC. The time from arrival in the Emergency Department to discharge or admission to the hospital was unchanged after the introduction of FilmArray GI panel, but length of hospital stay was shorter (3 vs. 7.5 days, p = 0.0002) for the FilmArray group. The time to empiric antibiotics did not differ significantly, but optimal antibiotics were started earlier after introduction of the FilmArray GI panel (hospital day 1 vs. 2, p < 0.0001). More patients were discharged without antibiotics after introduction of the FilmArray GI panel (14.0% vs. 4.5%; p < 0.001). CONCLUSION: Our results demonstrate that the FilmArray GI panel is an important tool for improving both patient care and antibiotic stewardship, despite the tendency for positive results with multiple pathogens.

Development of a telehealth intervention to promote care-seeking among transgender women of color in Washington, DC.

BACKGROUND: Transgender women of color (TWC) are an underserved population who often experience high rates of HIV and barriers to care including stigma, violence, and trauma. Few health information technology interventions are tailored to serve TWC. The purpose of this study was to inform the development of a TWC-specific telehealth intervention to increase access to care. METHODS: Formative qualitative semi-structured interviews and focus groups were conducted to develop a customized telehealth intervention for TWC. Participants were TWC ≥ 18 years living in the Washington, DC metropolitan area, with at least one structural barrier to care and clinicians ≥18 years who provide care to TWC. Transcripts were analyzed using thematic coding and content analysis; barriers for TWC were categorized into Individual, Organizational, and Environmental levels. Several day-long meetings with TWC and stakeholders were convened to develop the intervention. RESULTS: Saturation of theme on barriers to care was reached with 22 interviews. Identified barriers to service receipt included survival, instability, temporal discounting, and prioritizing hormone therapy over care, incongruence between providers and patients, pessimism, and lack of cultural competency. Each was intentionally addressed with the telehealth intervention. CONCLUSIONS: Data informed the development of an innovative and customized telehealth intervention for TWC. Through the integration of technology and peer consultant outreach, we developed a novel approach that can address population-specific challenges to care. Further development of this model may be able to improve health outcomes among TWC.

A Randomized Controlled Pilot Study of a Culturally-Tailored Counseling Intervention to Increase Uptake of HIV Pre-exposure Prophylaxis Among Young Black Men Who Have Sex with Men in Washington, DC.

Daily emtricitabine/tenofovor is effective at preventing HIV acquisition and is approved for HIV pre-exposure prophylaxis (PrEP). Blacks in the United States have a disproportionately high rate of HIV, and uptake of PrEP has been very low in this population. We conducted a pilot study in a high-prevalence city to test whether a culturally-tailored counseling center for young Black men who have sex with men (BMSM) positively impacted their access and uptake of PrEP. 50 young BMSM were randomized to either a PrEP counseling center group or a control group, and were then encouraged to obtain PrEP from a PrEP provider. At the end of 3 month study, six participants in the intervention group compared with none in the control group had initiated PrEP (p = 0.02). This pilot study demonstrates that a culturally-tailored counseling center might be an effective at increasing the uptake of PrEP in young BMSM.

Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Women: A Phase 2 Randomized Trial.

BACKGROUND: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). OBJECTIVE: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. DESIGN: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114). SETTING: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. PARTICIPANTS: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. INTERVENTION: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). MEASUREMENTS: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. RESULTS: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. LIMITATIONS: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. CONCLUSION: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroc-containing PrEP for women may warrant further study. PRIMARY FUNDING SOURCE: National Institutes of Health.

Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073.

Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection.

Mycobacterium fortuitum empyema associated with an indwelling pleural catheter: Case report and review of the literature.

Mycobacterium fortuitum is a rapidly growing mycobacterium (RGM) that is an uncommon cause of healthcare-associated infections. The most common infections caused by M. fortuitum include skin, soft tissue, and catheter-related infections. Although occasionally cultured from sputum samples, M. fortuitum is a rare cause of pulmonary disease. We report a case of M. fortuitum empyema associated with an infected pleural catheter and review M. fortuitum pulmonary infections.

Pneumocystis jirovecii Pneumonia in Human Immunodeficiency Virus Infection.

The presentation of Pneumocystis pneumonia (PCP) in previously healthy men having sex with men (MSM) in San Francisco and New York City in 1981 heralded the beginning of the human immunodeficiency virus (HIV) pandemic. Despite a decreasing incidence of PCP among patients with HIV/AIDS (acquired immunodeficiency syndrome) since the advent of combination antiretroviral therapy in the mid-1990s, PCP remains one of the most common AIDS-defining opportunistic infections in the United States and Western Europe. Newer molecular diagnostic tests in conjunction with standard immunofluorescent or colorimetric tests have allowed for more rapid and accurate diagnosis. Although several effective oral and intravenous therapies exist to treat PCP, mortality rates in HIV-infected individuals remain unacceptably high, especially in those with advanced AIDS. The identification of specific mutations in Pneumocystis genes targeted by trimethoprim-sulfamethoxazole has raised concerns about the development of resistance to the drug of choice and may ultimately lead to greater utilization of alternative therapies to treat PCP in the future.

Combined endoscopic cyclophotocoagulation and phacoemulsification versus phacoemulsification alone in the treatment of mild to moderate glaucoma.

BACKGROUND: To evaluate the long-term effects of combined endoscopic cyclophotocoagulation and phacoemulsification (phaco) versus phacoemulsification alone on intraocular pressure control and medication reliance in the treatment of mild to moderate glaucoma. DESIGN: Retrospective chart review in private practice setting by glaucoma fellowship trained surgeons. PARTICIPANTS: A total of 261 eyes in the combined phaco-endoscopic cyclophotocoagulation group with 52 eyes in the phaco-alone group. METHODS: Comparison of phaco-endoscopic cyclophotocoagulation with phaco alone over 36 months. MAIN OUTCOME MEASURES: Full and qualified success cumulative survival, intraocular pressure and medication reliance 6-36 months compared with baseline. Full success was defined as minimum 20% intraocular pressure reduction with a decrease of at least one ocular hypertensive medication. Qualified success was defined as intraocular pressure no higher than baseline with a decrease of at least one ocular hypertensive medication. RESULTS: At 36 months, mean intraocular pressure in the combined phaco-endoscopic cyclophotocoagulation group was 14.6 mmHg, whereas the phaco-alone group was 15.5 mmHg (P = 0.34). Mean medication reliance in the combined phaco-endoscopic cyclophotocoagulation group was 0.2 medications, whereas the phaco-alone group was 1.2 (P < 0.001). Full success in the phaco-endoscopic cyclophotocoagulation group was 61.4%; the phaco-alone group was 23.3% (P < 0.001). Qualified success survival was 72.6% in the phaco-endoscopic cyclophotocoagulation group and 23.3% in the phaco-alone group (P < 0.001). CONCLUSIONS: Combined phaco-endoscopic cyclophotocoagulation effectively lowers or maintains intraocular pressure and results in ocular hypertensive medication reduction up to 36 months when compared with phaco alone. Therefore, phaco-endoscopic cyclophotocoagulation may help to increase medication compliance and reduce glaucoma progression in mild to moderate glaucoma.

Clinical PathoScope: rapid alignment and filtration for accurate pathogen identification in clinical samples using unassembled sequencing data.

BACKGROUND: The use of sequencing technologies to investigate the microbiome of a sample can positively impact patient healthcare by providing therapeutic targets for personalized disease treatment. However, these samples contain genomic sequences from various sources that complicate the identification of pathogens. RESULTS: Here we present Clinical PathoScope, a pipeline to rapidly and accurately remove host contamination, isolate microbial reads, and identify potential disease-causing pathogens. We have accomplished three essential tasks in the development of Clinical PathoScope. First, we developed an optimized framework for pathogen identification using a computational subtraction methodology in concordance with read trimming and ambiguous read reassignment. Second, we have demonstrated the ability of our approach to identify multiple pathogens in a single clinical sample, accurately identify pathogens at the subspecies level, and determine the nearest phylogenetic neighbor of novel or highly mutated pathogens using real clinical sequencing data. Finally, we have shown that Clinical PathoScope outperforms previously published pathogen identification methods with regard to computational speed, sensitivity, and specificity. CONCLUSIONS: Clinical PathoScope is the only pathogen identification method currently available that can identify multiple pathogens from mixed samples and distinguish between very closely related species and strains in samples with very few reads per pathogen. Furthermore, Clinical PathoScope does not rely on genome assembly and thus can more rapidly complete the analysis of a clinical sample when compared with current assembly-based methods. Clinical PathoScope is freely available at: http://sourceforge.net/projects/pathoscope/.

Single-molecule long-read 16S sequencing to characterize the lung microbiome from mechanically ventilated patients with suspected pneumonia.

In critically ill patients, the development of pneumonia results in significant morbidity and mortality and additional health care costs. The accurate and rapid identification of the microbial pathogens in patients with pulmonary infections might lead to targeted antimicrobial therapy with potentially fewer adverse effects and lower costs. Major advances in next-generation sequencing (NGS) allow culture-independent identification of pathogens. The present study used NGS of essentially full-length PCR-amplified 16S ribosomal DNA from the bronchial aspirates of intubated patients with suspected pneumonia. The results from 61 patients demonstrated that sufficient DNA was obtained from 72% of samples, 44% of which (27 samples) yielded PCR amplimers suitable for NGS. Out of the 27 sequenced samples, only 20 had bacterial culture growth, while the microbiological and NGS identification of bacteria coincided in 17 (85%) of these samples. Despite the lack of bacterial growth in 7 samples that yielded amplimers and were sequenced, the NGS identified a number of bacterial species in these samples. Overall, a significant diversity of bacterial species was identified from the same genus as the predominant cultured pathogens. The numbers of NGS-identifiable bacterial genera were consistently higher than identified by standard microbiological methods. As technical advances reduce the processing and sequencing times, NGS-based methods will ultimately be able to provide clinicians with rapid, precise, culture-independent identification of bacterial, fungal, and viral pathogens and their antimicrobial sensitivity profiles.

Polymicrobial pericarditis caused by bacterial and fungal translocation from an oesophageal ulcer.

This case report discusses a rare instance of polymicrobial pericarditis in a man in his early 60s with a history of substance abuse. The patient presented with chest pain and shortness of breath, later diagnosed as pericarditis caused by Streptococcus anginosus, S. intermedius and Candida glabrata, likely originating from a large adjacent oesophageal ulcer. The condition led to critical illness, requiring pericardiocentesis, antibiotic and antifungal therapy. Despite initial improvement, the patient experienced recurrence and ultimately underwent pericardectomy. The article emphasises the rarity and severity of polymicrobial pericarditis, often associated with high mortality. It underscores the importance of prompt recognition, broad-spectrum antibiotics and source control, particularly when the gastrointestinal tract is implicated. The case highlights the challenges in managing such cases and the potential need for surgical intervention for optimal outcomes.

HIV-1 latency reversal and immune enhancing activity of IL-15 is not influenced by sex hormones.

The role of different biological variables including biological sex, age, and sex hormones in Human immunodeficiency virus (HIV) cure approaches is not well understood. The γc-cytokine IL-15 is a clinically relevant cytokine that promotes immune activation and mediates HIV reactivation from latency. In this work, we examined the interplay that biological sex, age, and sex hormones 17ß-estradiol, progesterone, and testosterone may have on the biological activity of IL-15. We found that IL-15-mediated CD4+ T cell activation was higher in female donors than in male donors. This difference was abrogated at high 17ß-estradiol concentration. Additionally, there was a positive correlation between age and both IL-15-mediated CD8+ T cell activation and IFN-γ production. In a primary cell model of latency, biological sex, age, or sex hormones did not influence the ability of IL-15 to reactivate latent HIV. Finally, 17ß-estradiol did not consistently affect reactivation of translation-competent reservoirs in CD4+ T cells from people living with HIV who are antiretroviral therapy (ART) suppressed. Our study has found that biological sex and age, but not sex hormones, may influence some of the biological activities of IL-15. Understanding how different biological variables may affect HIV cure therapies will help us evaluate current and future clinical trials aimed toward HIV cure in diverse populations.

Dual role of circulating and mucosal Vδ1 T cells in the control of and contribution to persistent HIV-1 infection.

Curative strategies for human immunodeficiency virus (HIV-1) infection are hindered by incomplete characterization of the latent reservoir and limited enhancement of anti-HIV immune responses. In this study, we identified a novel dual role for peripheral and tissue-resident Vδ1 T cells within the gastrointestinal mucosa of virally suppressed people with HIV. Phenotypic analyses identified an increased frequency of highly differentiated, cytotoxic effector Vδ1 T cells that exerted potent inhibition of HIV-1 replication in vitro coinciding with direct increases in cytolytic function. Conversely, we detected an enrichment of HIV-1 DNA in tissue-resident CD4+Vδ1 T cells in situ. Despite low CD4 expression, we found circulating Vδ1 T cells also contained HIV-1 DNA which was replication-competent. We show that TCR-mediated activation of peripheral Vδ1 T cells induced de novo upregulation of CD4 providing a plausible mechanism for increased permissibility to infection. These findings highlight juxtaposing roles for Vδ1 T cells in HIV-1 persistence including significant contribution to tissue reservoirs.

Cryptococcal pneumonia and meningitis in a renal transplant recipient with a false negative serum cryptococcal antigen due to postzone phenomenon.

Cryptococcal infection can cause significant morbidity and mortality in immunocompromised patients. We present a patient who was diagnosed with cryptococcal meningitis and pulmonary disease in the setting of a history of renal transplantation. The diagnosis was made based on growth of Cryptococcus neoformans in blood cultures and identification of cryptococcal antigen (CrAg) in cerebral spinal fluid (CSF) using a lateral flow assay (LFA). Our case is unique since the initial serum CrAg was falsely negative due to excess cryptococcal antigen preventing the formation of antigen-antibody complexes, referred to as the postzone phenomenon. This phenomenon has been reported on CSF samples but rarely reported on serum samples in patients without an HIV diagnosis.

Overcoming structural barriers to diffusion of HIV pre-exposure prophylaxis.

HIV prevention with antiretroviral medication in the form of pre-exposure prophylaxis (PrEP) offers a critical tool to halt the HIV pandemic. Barriers to PrEP access across drug types, formulations, and delivery systems share remarkable commonalities and are likely to be generalizable to future novel PrEP strategies. Appreciation of these barriers allows for planning earlier in the drug-development pathway rather than waiting for the demonstration of efficacy. The purpose of this article is to propose a core set of considerations that should be included in the drug-development process for future PrEP interventions. A literature synthesis of key barriers to PrEP uptake in the United States was conducted to elucidate commonalities across PrEP agents and delivery methods. Based on the published literature, we divided challenges into three main categories of structural barriers: (1) provider and clinic characteristics; (2) cost considerations; and (3) disparities and social constructs, with potential solutions provided for each. Pragmatic strategies for examining and overcoming these barriers before future PrEP regulatory approval are recommended. If these strategies are considered well before the time of commercial availability, the potential for PrEP to interrupt the HIV pandemic will be greatly enhanced.

Overcoming Barriers to Diffusion of HIV PrEP Giving antiretroviral medications to prevent acquiring HIV is called pre-exposure prophylaxis or PrEP. PrEP offers a critical tool to halt the HIV pandemic. Unfortunately, there are many barriers to PrEP access. Whether the PrEP is a pill, an injection, or other drug delivery systems not yet created, they share many common characteristics. Understanding these barriers now can help us plan earlier in the drug-development process rather than waiting for proof that the medication works. We can start overcoming barriers to PrEP access if we think of them before the drugs are developed rather than waiting until they are on the market. The purpose of this article is to propose core considerations to include in the drug-development process for future PrEP methods. The authors conducted a literature synthesis examining key barriers to PrEP uptake in the United States. The published literature was reviewed to identify commonalities across PrEP drugs and delivery methods. Based on the published literature, the authors divided challenges into three main categories: (1) provider and clinic characteristics; (2) cost considerations; and (3) disparities and social constructs. Potential solutions are provided for each. Practical strategies for examining and overcoming these barriers before future PrEP regulatory approval are recommended. If these strategies are considered before the time of commercial availability, the potential for PrEP to stop HIV will be greatly enhanced.