Host Nuclear Genome Copy Number Variations Identify High-Risk Anal Precancers in People Living With HIV.

BACKGROUND: People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. In this study, specific chromosomal variants were identified in anal squamous intraepithelial lesions. METHODS: Overall, 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) were collected from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological, and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using fluorescence in situ hybridization, and analyses compared the associations of these alterations with clinical characteristics. RESULTS: Gains of 3q26, 5p15, 20q13, and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared with 7%, 0%, 4%, and 0% of LSIL, respectively. If at least 1 abnormality was observed, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other 3 alterations. The sensitivity and specificity of any alteration to predict HSIL were 47% (95% CI: 30%-65%) and 93% (95% CI: 76%-99%), respectively. CONCLUSIONS: Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13, and/or chr7. IMPACT: Insights into potential genomic biomarkers for discriminating high-risk anal precancers are shared.

Clinical Characteristics and Outcomes of Patients With Mpox Who Received Tecovirimat in a New York City Health System.

Background: The 2022 global mpox outbreak was notable for transmission between persons outside of travel and zoonotic exposures and primarily through intimate contact. An understanding of the presentation of mpox in people with human immunodeficiency virus (HIV) and other immunocompromising conditions and knowledge of the efficacy of tecovirimat continue to evolve. Methods: This retrospective study describes clinical features and outcomes of persons with mpox who received tecovirimat. Data were obtained via medical record review of patients prescribed tecovirimat in a health system in New York City during the height of the outbreak in 2022. Results: One hundred thirty people received tecovirimat between 1 July and 1 October 2022. People with HIV (n = 80) experienced similar rates of recovery, bacterial superinfections, and hospitalization compared to patients without immunocompromising conditions. Individuals determined to be severely immunocompromised (n = 14) had a higher risk of hospitalization than those without severe immunocompromise (cohort inclusive of those with well-controlled HIV, excluding those without virologic suppression, n = 101): 50% versus 9% (P < .001). Hospitalized patients (n = 18 [13% of total]) were primarily admitted for bacterial superinfections (44.4%), with a median hospital stay of 4 days. Of those who completed follow-up (n = 85 [66%]), 97% had recovery of lesions at time of posttreatment assessment. Tecovirimat was well tolerated; there were no reported severe adverse events attributed to therapy. Conclusions: There were no significant differences in outcomes between people with HIV when evaluated as a whole and patients without immunocompromising conditions. However, mpox infection was associated with higher rates of hospitalization in those with severe immunocompromise, including patients with HIV/AIDS. Treatment with tecovirimat was well tolerated.Key Points: In our mpox cohort, people with HIV had similar rates of recovery and complications as those without HIV or other immunocompromising conditions. Severe immunocompromise was associated with a higher hospitalization rate. Tecovirimat was well tolerated, with minimal side effects.

Attitudes Toward Peer-Delivered Sexual-Health Services Among New York City Sexual and Gender Minority Individuals Who Have Sex with Men and Attend Collective Sex Venues.

Collective sex venues such as sex clubs are strategic sites to promote sexual health among sexual and gender minority individuals. We present qualitative findings from a multiple-method study on the acceptability of sexual-health services at collective sex venues in New York City (NYC) among attendees who identified as men, transgender, or gender non-conforming. In a survey used for sample selection (n = 342), most respondents (82.7%) agreed that "having outreach workers at sex venues is a good thing." Interviewees (n = 30) appreciated how on-site services could promote sexual health in their community. They felt peer workers should be familiar with collective sex venues and share demographic characteristics with attendees. Some participants felt workers should keep some boundaries from attendees, while others felt they could be fully integrated in the environment, suggesting that either peer outreach or popular-opinion leader types of interventions could be feasible.

Everybody nose: molecular and clinical characteristics of nasal colonization during active methicillin-resistant Staphylococcus aureus bloodstream infection.

BACKGROUND: Healthcare-associated infections pose a potentially fatal threat to patients worldwide and Staphylococcus aureus is one of the most common causes of healthcare-associated infections. S. aureus is a common commensal pathogen and a frequent cause of bacteremia, with studies demonstrating that nasal and blood isolates from single patients match more than 80% of the time. Here we report on a contemporary collection of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections to evaluate the diversity within hosts, and detail the clinical features associated with concomitant nasal colonization. METHODS: Swabs of the bilateral anterior nares were obtained from patients diagnosed with MRSA bacteremia. A single colony culture from the blood and an average of 6 colonies from the nares were evaluated for MRSA growth. For the nares cultures, we typed multiple isolates for staphylococcal protein A (spa) and derived the clonal complexes. Demographic and clinical data were obtained retrospectively from the electronic medical record system and analysed using univariate and multivariable regression models. RESULTS: Over an 11-month period, 68 patients were diagnosed with MRSA bloodstream infection, 53 were swabbed, and 37 (70%) were colonized with MRSA in the anterior nares. We performed molecular typing on 213 nasal colonies. Spa types and clonal complexes found in the blood were also detected in the nares in 95% of the cases. We also found that 11% of patients carried more than one clone of MRSA in the nares. Male sex and history of prior hospitalization within the past 90 days increased odds for MRSA colonization. CONCLUSION: The molecular epidemiological landscape of colonization in the setting of invasive disease is diverse and defining the interplay between colonization and invasive disease is critical to combating invasive MRSA disease.

The other side of screening: predictors of treatment and follow-up for anal precancers in a large health system.

BACKGROUND: Anal cancer disproportionately affects people with HIV (PWH). High-grade squamous intraepithelial lesions (HSIL) are cancer precursors and treating them might prevent anal cancer. Data on adherence to HSIL treatment and surveillance is limited but needed to identify deficiencies of screening strategies. METHODS: We collected data on high-resolution anoscopy (HRA) attendance and outcomes from 2009 to 2019 in a large urban anal cancer-screening program. Patients with an initial HSIL diagnosis were followed for return for HSIL electrocautery ablation within 6 months of index HSIL diagnosis, and follow-up HRA within 18 months of index HSIL diagnosis. We also evaluated predictors of these outcomes in univariable and multivariable analyses. RESULTS: One thousand one hundred and seventy-nine unique patients with an anal HSIL diagnosis were identified and 684 (58%) returned for electrocautery ablation. Of those treated, only 174 (25%) and only 9% of untreated HSIL patients (47 of 495) underwent surveillance HRA within 18 months of index HSIL diagnosis. In multivariable analyses, black patients and PWH regardless of virologic control were less likely to undergo HSIL ablation within 6 months of HSIL diagnosis whereas patients with commercial insurance were more likely to be treated within 6 months of diagnosis. Among treated HSIL patients, PWH with viremia had a lower likelihood of engaging in post-treatment surveillance within 18 months of HSIL diagnosis. DISCUSSION: Even in large specialized anal cancer screening programs adherence to HSIL treatment and surveillance is low. Psychosocial and economic determinants of health may impact retention in care. Addressing both personal and structural barriers to patient engagement may improve the effectiveness of anal cancer screening.

Comparing Anal Cancer Screening Algorithms Using Cytology and Human Papillomavirus DNA Testing in 3 High-Risk Populations.

BACKGROUND: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. METHODS: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). RESULTS: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36). CONCLUSIONS: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.

PrEP in the Real World: Predictors of 6-Month Retention in a Diverse Urban Cohort.

The effectiveness of HIV pre-exposure prophylaxis (PrEP) depends on adherence, which requires retention in PrEP care. We sought to examine factors associated with six-month retention in PrEP care among individuals prescribed PrEP between 2011 and 2015 in a large, academic health system in the Bronx, New York. We used multivariable logistic regression to identify factors independently associated with six-month retention. Among 107 patients, retention at 6 months was 42%. In the multivariable analysis, heterosexual individuals were less likely to be retained in PrEP care at 6 months, but individuals who received prescriptions from attending physicians were more likely to be retained in care. Larger prospective studies are needed to better evaluate the individual and health system factors associated with long-term engagement in PrEP care.

Development and evaluation of a pilot overdose education and naloxone distribution program for hospitalized general medical patients.

Background: Overdose education and naloxone distribution (OEND) to people at risk of witnessing or experiencing an opioid overdose has traditionally been provided through harm reduction agencies. Expanding OEND to inpatient general medical settings may reach at-risk individuals who do not access harm reduction services and have not been trained. An OEND program targeting inpatients was developed, piloted, and evaluated on 2 general medicine floors at Montefiore Medical Center, a large urban academic medical center in Bronx, New York. Methods: The planning committee consisted of 10 resident physicians and 2 faculty mentors. A consult service model was piloted, whereby the primary inpatient care team paged the consult team (consisting of rotating members from the planning committee) for any newly admitted patient who had used any opioid in the year prior to admission. Consult team members assessed patients for eligibility and provided OEND to eligible patients through a short video training. Upon completion, patients received a take-home naloxone kit. To evaluate the program, a retrospective chart review over the first year (April 2016 to March 2017) of the pilot was conducted. Results: Overall, consults on 80 patients were received. Of these, 74 were eligible and the consult team successfully trained 50 (68%). Current opioid analgesic use of ≥50 morphine milligram equivalents daily was the most common eligibility criterion met (38%). Twenty-four percent of patients were admitted for an opioid-related adverse event, the most common being opioid overdose (9%), then opioid withdrawal (8%), skin complication related to injecting (5%), and opioid intoxication (2%). Twenty-five percent had experienced an overdose, 35% had witnessed an overdose in their lifetime, and 83% had never received OEND previously. Conclusions: Integrating OEND into general inpatient medical care is possible and can reach high-risk patients who have not received OEND previously. Future research should identify the optimal way of implementing this service.

Targeted ablation of perianal high-grade dysplasia in men who have sex with men: an alternative to mapping and wide local excision.

BACKGROUND: Perianal high-grade dysplasia (Bowen disease) is traditionally treated with mapping and wide excision with possible grafting rather than local ablation. OBJECTIVE: The aim of this study is to examine the results of high-grade perianal dysplasia ablation. DATA SOURCES: Data for this study were derived from a retrospective chart review at a surgical practice screening and treating patients for high-grade dysplasia between July 1998 and June 2013. STUDY SELECTION: The patients included were men who have sex with men and are undergoing perianal dysplasia ablation. INTERVENTION: Ablation of perianal dysplasia with electrocautery, laser, or infrared coagulation was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the recurrence of perianal dysplasia postablation and factors affecting recurrence. RESULTS: Seventy HIV-positive and 11 HIV-negative patients enrolled; the median ages were 44.7 and 42.8 years. Median follow-up times for HIV-positive and HIV-negative patients were 4.62 and 3.53 years, and the median numbers of treatments were 4 and 1, p = 0.004. The median number of lesions treated was 1 for both groups. Only 1 HIV-negative patient had a recurrence 8 months after treatment. For HIV-positive patients, the Kaplan-Meier probability of recurrence at 1, 3, and 5 years was 38% (95% CI 26-50), 59% (95% CI 47-72), and 68% (95% CI 55-81) after the first ablation with no difference for subsequent treatments. HIV-positive patients had a relative risk of perianal high-grade squamous intraepithelial lesions of 3.72 (95% CI 2.10-6.60) compared with HIV-negative patients (p ≤ 0.0001). In multivariate analysis, only each increase in intra-anal high-grade squamous intraepithelial lesions significantly increased recurrence (HR 1.13, 95% CI 1.00-1.28, p = 0.002). Only 3 patients with perianal high-grade squamous intraepithelial lesions did not have canal dysplasia. Perianal cancer developed in 3 after being lost to follow-up. LIMITATIONS: This is a retrospective analysis of 1 experienced surgeon's results. No precise way exists to accurately determine the size of the disease. CONCLUSIONS: Perianal dysplasia can be successfully ablated, but recurrence remains high. Almost all patients have anal canal dysplasia. HIV-positive patients are at the greatest risk for disease and recurrence. An increased number of high-grade canal lesions increases recurrence.

Anal condyloma treatment and recurrence in HIV-negative men who have sex with men.

BACKGROUND: Men who have sex with men have increased prevalence of both human papillomavirus and anogenital condyloma. OBJECTIVE: Risk factors for multiple treatment and recurrence of anal condyloma were examined. DESIGN: This is a retrospective study of HIV-negative men who have sex with men who were treated for anal condyloma. SETTINGS: This study was conducted in a private surgical practice. PATIENTS: The patients were HIV-negative men who have sex with men, aged 18 years or older. INTERVENTION(S): Ablation with electrocautery or CO2 laser was performed, as well as excision and topical imiquimod condyloma treatment adjuvant. MAIN OUTCOME MEASURES: Primary clearance, defined as 4 months of condyloma-free survival posttreatment, and recurrence, defined as any anal condyloma diagnosis after primary clearance. RESULTS: Of 231 participants, 207 achieved primary clearance (median age, 32.0 years) and were followed (median, 18.2 months) after primary treatment. Most had intra-anal and perianal condyloma (56%), were treated with electrocautery ablation (79.2%), and required 1 treatment (range, 1-6) for clearance. There were 57 recurrences (median, 12 months). One-third each had minimal, moderate, or extensive disease. Forty-six percent of patients received imiquimod posttreatment adjuvant. High-grade dysplasia was found in 31% at presentation and 43% during follow-up. Factors associated with requiring multiple treatments for clearance were participants having moderate disease (adjusted odds ratio, 6.0 (1.7-21.4)) and receiving imiquimod adjuvant (adjusted odds ratio, 4.7 (2.0-10.6)). No single factor predicted recurrence, but those with moderate disease experienced recurrences significantly sooner (median, 25 months of follow-up). LIMITATIONS: This was a retrospective chart review, it was limited to a single practice, and it excluded those who did not achieve primary clearance. CONCLUSIONS: Most men who have sex with men have intra-anal and perianal condyloma and concomitant high-grade dysplasia is common. Most achieved clearance with 1 treatment. Having both intra-anal and perianal condyloma, increased severity of disease, and imiquimod adjuvant were significant predictors of requiring multiple treatments for clearance. No identified risk factors proved a significant predictor of recurrence.

Random biopsy during high-resolution anoscopy increases diagnosis of anal high-grade squamous intraepithelial lesions.

OBJECTIVE: Random biopsy (RB) of normal appearing cervix during colposcopy increases high-grade dysplasia (HSIL) diagnosis but has not been studied in high-resolution anoscopy (HRA), that is, colposcopy transferred to the anal canal. We investigated the utility of RB during HRA. DESIGN: At HRA, the anal canal was divided into 4 quadrants. Areas suspicious for HSIL had standard biopsy (SB); random biopsies were taken from quadrants without apparent HSIL. Inclusion required ≥1 RB. Two providers performed all procedures (S.E.G., >10 years experience; M.M.G. 3 years experience). RESULTS: Overall, 391 participants enrolled (mean age, 44.7 years); most were male (87.2%), non-Hispanic (69.8%), white (62.7%), and HIV positive (72.9%). Of 1761 biopsies, 883 were RBs (mean, 2.26/participant). HSIL was identified in 252 lesions, and in 132 participants (33.8%). Thirty-two HSILs (12.7%) and 13 participants (9.8%) were diagnosed by RB. RB increased total HSILs identified per participant (mean, 0.65 vs. 0.56; P < 0.001) and participants with HSIL (P < 0.001). Histologically, HSIL diagnoses via SB were no more dysplastic than random biopsies (relative risk, 0.82; range, 0.37-1.8). In multivariable analysis, factors affecting adjusted relative risk (ARR) of HSIL with any biopsy were provider [S.E.G vs. M.M.G.; ARR, 5.9; 95% confidence interval (CI), 1.3 to 25.8] and oncogenic human papillomaviral infection (ARR, 24.3; 95% CI, 2.8 to 213.3). Risk of HSIL on RB alone in multivariate analysis was associated with HSIL via SB (ARR, 3.4; 95% CI, 1.6 to 7.1 or ARR, 1.4; 95% CI, 1.1 to 1.9 per standard HSIL). Provider, HIV status, detectable viral load, age, or prior screening for or treatment of HSIL did not affect the utility of RB. CONCLUSIONS: Addition of RB to HRA significantly increased both the number of HSILs and participants with HSIL identified.

Viewing pornography depicting unprotected anal intercourse: are there implications for HIV prevention among men who have sex with men?

We used an Internet-based questionnaire to investigate whether viewing pornography depicting unprotected anal intercourse (UAI) was associated with engaging in UAI in a sample of 821 non-monogamous men who have sex with men (MSM). In the 3 months prior to interview, 77.2% viewed pornography depicting UAI, 42.6% engaged in insertive UAI, and 38.9% engaged in receptive UAI. Polytomous logistic regression of the 751 subjects who provided data on pornography viewing showed significantly elevated odds ratios for having engaged in receptive UAI, insertive UAI, and both receptive and insertive UAI associated with increasing percentage of pornography viewed that depicted UAI. We also found independently significant associations of engaging in UAI with age, use of inhalant nitrites, and HIV status. Although the data cannot establish causality, our findings indicate that viewing pornography depicting UAI and engaging in UAI are correlated. Further research is needed to determine if this observation may have utility for HIV prevention.

Awareness of post-exposure HIV prophylaxis in high-risk men who have sex with men in New York City.

OBJECTIVES: To understand the factors associated with knowledge of non-occupational post-exposure prophylaxis (nPEP) and pre-exposure prophylaxis (PrEP), bathhouse patrons in New York City (NYC) were surveyed. METHODS: 554 men who have sex with men (MSM) at two NYC bathhouses were given a standardised survey focused on nPEP and PrEP at the time of HIV testing. RESULTS: In the previous 90 days, 63% of respondents reported unprotected sex with a male partner and 7% reported any sex with a known HIV-positive male partner. Less than half reported having a primary provider (primary care practitioner) who was aware of their MSM behaviour. 201 men (36%) were aware of nPEP or PrEP. In univariate analyses, race/ethnicity, previous HIV testing, gay self-identification, higher education level, having a primary provider aware of MSM behaviour, reported interaction with the healthcare system, use of the internet for meeting sex partners, reporting unprotected sex in the previous 90 days, reporting any sex with an HIV-positive male partner in the previous 90 days and having a higher number of sex partners were each significantly associated with being aware of nPEP or PrEP. In multivariate analysis, having a higher number of sex partners was significantly associated (OR 5.10, p=0.02) with post-exposure prophylaxis (PEP)/PrEP knowledge and disclosure to a primary care provider was also associated, although less robustly (OR 2.10, p=0.06). CONCLUSIONS: Knowledge of nPEP or PrEP among sexually active MSM in NYC is low and is associated with having a primary provider aware of their patient's same-sex behaviours. These findings show the need for improving education about nPEP among high-risk MSM in NYC and the role of providers in these efforts.

The Development and Implementation of an Outreach Program to Identify Acute and Recent HIV Infections in New York City.

INTRODUCTION: Since 2004, the authors have been operating First Call NYU, an outreach program to identify acute and recent HIV infections, also called primary HIV infections, among targeted at-risk communities in the New York City (NYC) metropolitan area. MATERIALS AND METHODOLOGY: First Call NYU employed mass media advertising campaigns, outreach to healthcare providers in NYC, and Internet-based efforts including search engine optimization (SEO) and Internet-based advertising to achieve these goals. RESULTS: Between October 2004 and October 2008, 571 individuals were screened through this program, leading to 446 unique, in-person screening visits. 47 primary HIV infections, including 14 acute and 33 recent HIV infections, were identified. DISCUSSION: Internet and traditional recruitment methods can be used to increase self-referrals for screening following possible exposure to HIV. CONCLUSION: Community education of at-risk groups, with the goal of increased self-diagnosis of possible acute HIV infection, may be a useful addition to traditional efforts to identify such individuals.

Implementation of HIV testing at 2 New York City bathhouses: from pilot to clinical service.

BACKGROUND: Commercial sex venues (e.g., bathhouses) that cater to men who have sex with men (MSM) continue to function in most urban areas. These venues present a challenge to developing strategies to prevent the spread of the human immunodeficiency virus (HIV), but they also provide opportunities for interventions to reduce the risk and rate of disease transmission. Several cities in the United States have developed programs that offer HIV testing in these venues. Similar programs have not existed before in New York City. METHODS: A pilot HIV testing program was implemented at 2 New York City bathhouses. Testing included rapid HIV testing, the use of the serologic testing algorithm for recent HIV seroconversion, and pooled plasma HIV viral load to detect and date incident and acute HIV infections. In addition to HIV tests, behavioral and demographic data were collected from 493 presumed HIV-negative participants. RESULTS: The pilot program recruited MSM who were at high risk for HIV infection. Of the 493 men tested, 20 (4%) were found to be positive for HIV, and 8 (40%) of these 20 men demonstrated evidence of acute or recent HIV infection. The program tested men often not tested in more traditional medical settings. Significant disparities were demonstrated in the testing habits of MSM who reported having sex with women and had not disclosed same-sex activities to their caregivers. CONCLUSIONS: Bathhouse-based testing for HIV infection can be implemented in New York City and would include a population of MSM who are at high risk for HIV infection. Because of the high rate of recent HIV infection, expanded testing in these venues may be a good strategy to reduce the forward transmission of HIV in this highly sexually active population.