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.

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 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 examine 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 compared to 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 ART-suppressed people living with HIV. 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 affect the biological activity of cure therapies will help us evaluate current and future clinical trials aimed towards HIV cure in diverse populations.

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.

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.

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.

"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.

Double trouble: Concomitant unmasking and paradoxical immune reconstitution inflammatory syndrome in a patient with newly diagnosed HIV.

Immune reconstitution inflammatory syndrome (IRIS) is a complication encountered in patients with HIV due to immune function recovery following the initiation of antiretroviral therapy. IRIS can be divided into two forms: paradoxical (recurrence of clinical signs of a previously treated opportunistic infection) and unmasking (uncovering of a previously undiagnosed and asymptomatic infection). We present the rare case of a 48-year-old man diagnosed with AIDS after presenting with cryptococcal meningitis who, shortly after initiation of ART, developed both unmasking IRIS due to Mycobacterium avium complex (MAC), and subsequently paradoxical IRIS to his prior cryptococcal meningitis infection. To our knowledge, cases in the medical literature describing "double IRIS" remain scarce.

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.

A dynamic risk-based approach to managing a pandemic.

A pandemic is a unique natural disaster that will pose challenges for any organisation. During the COVID-19 pandemic, for example, organisations of all types have struggled to maintain operations while assuring the health and wellbeing of the various persons who work on their behalf. Certainly, many organisations have found that their risk management and business continuity plans fail to consider adequately the disruption associated with a pandemic caused by a novel pathogen. As this paper discusses, this suggests a need to revisit risk assessments and business impact analyses; the assumptions and timeframes on which they are based; and the plans that they have generated. The paper argues that static plans are ill-suited to address the evolving threat of pandemic, and that effective planning and management of pandemic response must be dynamic in nature.

Ureaplasma septic polyarthritis in a young woman with neuromyelitis optica receiving rituximab.

We report a case of septic polyarthritis caused by Ureaplasma urealyticum in a woman with neuromyelitis optica who was receiving rituximab. Her case exemplifies some of the unique characteristics of invasive Ureaplasma infections that can lead to delayed diagnosis as well as treatment challenges including recurrence following antibiotic discontinuation.

Impact of Infectious Disease Consultation in Patients With Candidemia: A Retrospective Study, Systematic Literature Review, and Meta-analysis.

BACKGROUND: Morbidity and mortality from candidemia remain unacceptably high. While infectious disease consultation (IDC) is known to lower the mortality from Staphylococcus aureus bacteremia, little is known about the impact of IDC in candidemia. METHODS: We conducted a retrospective observational cohort study of candidemia patients at a large tertiary care hospital between 2015 and 2019. The crude mortality rate was compared between those with IDC and without IDC. Then, we systematically searched 5 databases through February 2020 and performed a meta-analysis of the impact of IDC on the mortality of patients with candidemia. RESULTS: A total of 151 patients met the inclusion criteria, 129 (85%) of whom received IDC. Thirty-day and 90-day mortality rates were significantly lower in the IDC group (18% vs 50%; P = .002; 23% vs 50%; P = .0022, respectively). A systematic literature review returned 216 reports, of which 13 studies including the present report fulfilled the inclusion criteria. Among the 13 studies with a total of 3582 patients, IDC was performed in 50% of patients. Overall mortality was 38.2% with a significant difference in favor of the IDC group (28.4% vs 47.6%), with a pooled relative risk of 0.41 (95% CI, 0.35-0.49). Ophthalmology referral, echocardiogram, and central line removal were performed more frequently among patients receiving IDC. CONCLUSIONS: This study is the first systematic literature review and meta-analysis to evaluate the association between IDC and candidemia mortality. IDC was associated with significantly lower mortality and should be considered in all patients with candidemia.

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.

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.

A case of Mycobacterium goodii infection related to an indwelling catheter placed for the treatment of chronic symptoms attributed to Lyme disease.

Mycobacterium goodii has only rarely been reported to cause invasive disease in humans. Previously reported cases of M. goodii infection have included prosthetic joint infections, pacemaker pocket infections, and pneumonia. We present a case of M. goodii bacteremia with concomitant pulmonary septic emboli that developed in a 32-year-old woman with an indwelling central venous catheter (CVC). The CVC had been placed one year previously for intermittent treatment with intravenous, broadspectrum antibiotics, administered by an outside physician for the treatment of symptoms attributed to chronic Lyme disease. Despite our recommendations, the patient declined follow-up in our Infectious Diseases clinic, opting to continue care under her chronic Lyme disease physician. This case clearly demonstrates the potential for serious medical complications that can arise from the inappropriate use of longterm intravenous antibiotics using a CVC to treat non-specific symptoms attributed to Lyme disease and patients should be counseled regarding these risks.

Postoperative Complications of Ab Interno Gelatin Microstent.

PURPOSE: To report 4 previously undescribed postoperative complications in 4 cases of ab interno XEN45 Gel Stent (XEN) implantation following uncomplicated surgeries. PATIENTS AND METHODS: A total of 51 consecutive XEN implantations performed between July 1, 2017 and April 30, 2018 were reviewed. All cases were performed by 7 experienced glaucoma surgeons affiliated with the William Beaumont Hospital, Department of Ophthalmology. Cases with postoperative complications were identified, and a literature review was performed on PubMed.gov between April 5, 2018 and June 2, 2018 to identify previously unreported XEN complications. RESULTS: Case 1 consisted of an 86-year-old woman who suffered a suprachoroidal hemorrhage and associated rhegmatogenous retinal detachment following XEN implantation. One month after sclerotomy drainage and pars plana vitrectomy repair, an amputated XEN was found to have eroded through the conjunctiva. Case 2 consisted of a 68-year-old man with persistent elevated intraocular pressure due to recurrent Tenon's capsule fibrosis who developed complete XEN retraction into the subconjunctival space. Cases 3 and 4 consisted of a 68-year-old man and a 78-year-old woman who developed occlusion of the microstent's internal ostium by a partially detached Descemet's membrane. Case 3 maintained normal intraocular pressure on timolol, whereas case 4 resulted in bleb failure, despite Nd:YAG laser lysis of the occluded XEN internal ostium. CONCLUSIONS: Although the XEN is a promising new surgical option for the management of primary open-angle glaucoma, it can present unique postoperative challenges that are still being elucidated. Timely intervention or prevention of these complications can be improved by early surgeon recognition and effective communication with comanaging ophthalmologists.

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.

Streptobacillus moniliformis mitral valve endocarditis and septic arthritis: the challenges of diagnosing rat-bite fever endocarditis.

Streptobacillus moniliformis, the cause of rat-bite fever (RBF) in the United States, has rarely been reported as a cause of infectious endocarditis. In the majority of previously reported cases, the diagnosis was clinically- based in patients with underlying valvular abnormalities in the setting of positive blood culture for Streptobacillus moniliformis. We report a case of native valve endocarditis secondary to Streptobacillus moniliformis in a woman with a mitral valve vegetation but negative blood cultures where the diagnosis was established using molecular diagnostics on the valvular tissue.

Sexually Transmitted Infections Among HIV-Infected Individuals in the District of Columbia and Estimated HIV Transmission Risk: Data From the DC Cohort.

BACKGROUND: Washington, DC, has one of the highest rates of HIV infection in the United States. Sexual intercourse is the leading mode of HIV transmission, and sexually transmitted infections (STIs) are a risk factor for HIV acquisition and transmission. METHODS: We evaluated the incidence and demographic factors associated with chlamydia, gonorrhea, and syphilis among HIV-infected persons enrolled at 13 DC Cohort sites from 2011 to 2015. Using Poisson regression, we assessed covariates of risk for incident STIs. We also examined HIV viral loads (VLs) at the time of STI diagnosis as a proxy for HIV transmission risk. RESULTS: Six point seven percent (451/6672) developed an incident STI during a median follow-up of 32.5 months (4% chlamydia, 3% gonorrhea, 2% syphilis); 30% of participants had 2 or more STI episodes. The incidence rate of any STIs was 3.8 cases per 100 person-years (95% confidence interval [CI], 3.5-4.1); age 18-34 years, 10.8 (95% CI, 9.7-12.0); transgender women, 9.9 (95% CI, 6.9-14.0); Hispanics, 9.2 (95% CI, 7.2-11.8); and men who have sex with men (MSM), 7.7 (95% CI, 7.1-8.4). Multivariate Poisson regression showed younger age, Hispanic ethnicity, MSM risk, and higher nadir CD4 counts to be strongly associated with STIs. Among those with an STI, 41.8% had a detectable VL within 1 month of STI diagnosis, and 14.6% had a VL ≥1500 copies/mL. CONCLUSIONS: STIs are highly prevalent among HIV-infected persons receiving care in DC. HIV transmission risk is considerable at the time of STI diagnosis. Interventions toward risk reduction, antiretroviral therapy adherence, and HIV virologic suppression are critical at the time of STI evaluation.