Skating on thin ice: stimulant use and sub‐optimal adherence to HIV pre‐exposure prophylaxis

IntroductionStimulant and heavy alcohol use are prevalent and associated with elevated risk for HIV seroconversion among men who have sex with men (MSM) and transgender women. In addition, each can pose difficulties for antiretroviral adherence among people living with HIV. Scant research has examined the associations of stimulant and heavy alcohol use with adherence to daily oral pre‐exposure prophylaxis (PrEP) among MSM and transgender women. To address this gap in the literature, we evaluated the hypothesis that stimulant use and binge drinking are prospectively associated with sub‐optimal PrEP adherence.MethodsWe analysed data from participants in a nested case‐cohort in the iPrEx open label extension. Stimulant use (i.e. powder cocaine, crack‐cocaine, cocaine paste, methamphetamine, cathinone) and binge drinking (i.e. ≥5 drinks in a single day) in the last 30 days were assessed. Baseline urine was tested for stimulants using immunoassays to reduce misclassification. Sub‐optimal adherence was defined as tenofovir drug concentrations in dried blood spots less than 700 fmol per punch, indicative of less than four doses per week. We tested the prospective association of stimulant use and binge drinking with sub‐optimal adherence at the 4‐week follow‐up visit.Results and DiscussionData from 330 participants were analysed. The majority of the participants were MSM (89%) with a median age at baseline of 29 years (interquartile range 24 to 39). Approximately 16% (52/330) used stimulants and 22% (72/330) reported binge drinking in the last 30 days. Stimulant users had fivefold greater odds of sub‐optimal PrEP adherence compared to non‐users in adjusted analysis (adjusted odds ratio [aOR] 5.04; [95% CI 1.35 to 18.78]). Self‐reported binge drinking was not significantly associated with sub‐optimal adherence after adjusting for stimulant use and baseline confounders (aOR 1.16 [0.49 to 2.73]). Depressive symptoms, being transgender, and number of sex partners were also not significantly associated with sub‐optimal PrEP adherence (p > 0.05).ConclusionsStimulant use is a risk factor for sub‐optimal PrEP adherence in the month following PrEP initiation. Comprehensive prevention approaches that reduce stimulant use may optimize PrEP adherence. Creating adherence plans that specifically address PrEP dosing in the context of ongoing stimulant use should also be considered.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142946/1/jia225103.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142946/2/jia225103_am.pd

Gender-Affirming Mastectomy Trends and Surgical Outcomes in Adolescents

BackgroundThere are over 150,000 transgender adolescents in the United States, yet research on outcomes following gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence, as well as postoperative complications, including regret, in adolescents within our integrated health care system.MethodsGender-affirming mastectomies performed from January 1, 2013 - July 31, 2020 in adolescents 12-17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth ages 12-17 within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using chi-squared tests.ResultsThe incidence of gender-affirming mastectomy increased 13-fold (3.7 to 47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range 12-17) and the most common technique was double-incision (85%). For patients with greater than 1-year follow-up (n=137, 65.6%), at least one complication was found in 7.3% (n=10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9 % underwent revision (n=15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (p>0.05). Two patients (0.95%) had documented postoperative regret but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively.ConclusionBetween 2013-2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low and of over 200 adolescents who underwent surgery, only two expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy

Sexual Behavior, Risk Compensation, and HIV Prevention Strategies Among Participants in the San Francisco PrEP Demonstration Project: A Qualitative Analysis of Counseling Notes

Abstract Pre-exposure prophylaxis (PrEP) is a viable HIV prevention strategy but risk compensation could undermine potential benefits. There are limited data that examine this phenomenon outside of clinical trials. We conducted a qualitative analysis of counseling notes from the San Francisco site of the US PrEP demonstration project to assess how men who have sex with men used PrEP as a prevention strategy and its impact on their sexual practices. Four major themes emerged from our analysis of 130 distinct notes associated with 26 participants. Prevention strategy decision-making was dynamic, often influenced by the context and perceived risk of a sexual encounter. Counselors noted that participants used PrEP in conjunction with other health promotion strategies like condoms, asking about HIV status of their sex partners, and seroadaptation. With few exceptions, existing risk reduction strategies were not abandoned upon initiation of PrEP. Risk-taking behavior was 'seasonal' and fluctuations were influenced by various personal, psychosocial, and healthrelated factors. PrEP also helped relieve anxiety regarding sex and HIV, particularly among serodiscordant partners. Understanding sexual decision-making and how PrEP is incorporated into existing prevention strategies can help inform future PrEP implementation efforts

The relationship of smoking and unhealthy alcohol use to the HIV care continuum among people with HIV in an integrated health care system

INTRODUCTION: Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination. METHODS: Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined. RESULTS: The overall sample (N=8,958) had a mean age of 48.0 years; was 91.3% male; 54.0% white, 17.6% Latino, 15.1% black, and 9.6% other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR=1.60 [95% CI 1.03–2.48]), not retained (OR=1.30 [95% CI 1.13–1.50]), and HIV RNA not in control (OR=1.91 [95% CI 1.60–2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR=2.83 [95% CI 1.40–5.71]), although the interaction did not reach significance (p=0.18). CONCLUSIONS: In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes

Inflammation and breast cancer. Metalloproteinases as common effectors of inflammation and extracellular matrix breakdown in breast cancer

Two rapidly evolving fields are converging to impact breast cancer: one has identified novel substrates of metalloproteinases that alter immune cell function, and the other has revealed a role for inflammation in human cancers. Evidence now shows that the mechanisms underlying these two fields interact in the context of breast cancer, providing new opportunities to understand this disease and uncover novel therapeutic strategies. The metalloproteinase class of enzymes is well studied in mammary gland development and physiology, but mostly in the context of extracellular matrix modification. Aberrant metalloproteinase expression has also been implicated in breast cancer progression, where these genes act as tumor modifiers. Here, we review how the metalloproteinase axis impacts mammary physiology and tumorigenesis and is associated with inflammatory cell influx in human breast cancer, and evaluate its potential as a regulator of inflammation in the mammary gland

Optimizing the Delivery of HIV Pre-Exposure Prophylaxis (PrEP): An Evaluation of Risk Compensation, Disengagement, and the PrEP Cascade

IntroductionTo inform the optimal implementation of HIV pre-exposure prophylaxis (PrEP), we conducted three studies that evaluated serodisclosure, identified correlates of PrEP disengagement, and characterized the PrEP cascade of care.MethodsStudy 1 examined the association of PrEP use with participant non-disclosure and lack of knowledge of partner HIV status in the iPrEx Open Label Extension (OLE). Study 2 examined the effects of stimulant use and binge drinking (i.e., ≥5 drinks on one occasion) on PrEP disengagement in a nested case-cohort in OLE. PrEP disengagement was defined as failure to show for a follow-up visit or tenofovir drug levels &lt;700fmol/punch. Study 3 characterized the PrEP cascade (i.e., seeking services, initiating PrEP, and retention in care) and identified predictors of non-retention among those who started PrEP in a clinic-based cohort of men who have sex with men in San Francisco.ResultsWe analyzed data from 1,184 participants in Study 1. PrEP use was not significantly associated with non-disclosure or lack of knowledge of partner status in adjusted analyses (p-values≥.16). However, relationship characteristics were significantly associated with both outcomes. Of the 330 MSM and transgender women included in Study 2, 16% used stimulants and 22% reported binge drinking in the previous three months. Stimulant users had more than 5-fold greater odds of PrEP disengagement (adjusted odds ratio [aOR]=5.24, 95% CI [1.64-16.76]). Binge drinking was not significantly associated with PrEP disengagement after adjusting for stimulant use and baseline confounders (aOR=0.78 [0.33-1.88]). Of the 344 men who sought PrEP services in Study 3, 268 (78%) initiated PrEP. Cost was the most commonly cited reason for not starting. Among patients who initiated PrEP, cumulative incidence of non-retention at 13 months was 38%. Men with an STI diagnosis at enrollment had a 79% greater rate of non-retention (adjusted hazard ratio [aHR]=1.79 [1.06-3.01]). ConclusionWe found no evidence to suggest that PrEP use is associated with non-disclosure or not knowing partner status. Comprehensive prevention approaches that enhance uptake, reduce stimulant use, and support PrEP adherence and persistence are needed to address the heightened risk of HIV infection of those who use stimulants and those with STI diagnoses