Faculty Bibliography

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one's sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one's HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP.

The subtle signs and symptoms of substance use disorder (SUD) often go unrecognized by physicians in training. Many times, this is because primary care physicians are not trained to recognize SUDs as free-standing medical illnesses that can be successfully treated, and require primary care interventions. Physicians-in-training at the residency level may not know what these disorders looks like in their early and active phases, nor in phases of recovery. Most young physicians have never had the opportunity to speak with patients who are actively working to recover or in long-term recovery. In 2008, a major NYC teaching hospital (Lenox Hill Hospital) began to require all first-year primary care internal medical residents to attend a 12-hour Physician Alcohol and Addiction Training Program (PAAT). This innovative program utilizes patients as teachers. Each physician is paired with an alcoholic or addicted patient in recovery and actively involved in AA. In a powerful reversal of the traditional doctor-patient relationship, the patients, or "buddies" act as 1:1 teachers and mentors for the resident physicians, providing a profound and personal window into the experience of alcoholism and addiction, and modeling positive treatment outcomes and recovery. This work with buddies is integrated, in real time, with the training provided by physician faculty. Buddies accompany their resident physicians to an AA meeting and provide them with an understanding of 12-step sober support meetings as a powerful treatment modality. Each Buddy-Resident pair processes their AA experience, dispelling common myths about sober support meetings and dire prognosis of alcoholism and addiction. Residents get to know their buddies as people with expertise to offer them, and not simply as patients. They administer several screening tools (MAST, CAGE, and AUDIT) to their buddies, who are asked to answer both as they would have when actively using, and as they would now, looking backward from their current perches in recovery. This provides residents insight into the defensiveness, minimization and denial that they will face when screening for SUDs, and the critical need for cultivating longitudinal primary care relationships. Residents then take full biopsychosocial histories, and are encouraged to follow their curiosity and ask the questions that they would never ask if their buddies were their patients. The program concludes with resident presentations of their buddies' histories of use and recovery, getting feedback from both faculty and peers. Data about resident ratings of the program, utilizing the Wilcoxon matched-pairs signed-ranks pre-and post-tests, will be presented, as well as results demonstrating robust changes in students' perceptions after buddy mentoring, with the emergence of an understanding that substance use is a chronic relapsing medical disease that can be successfully treated, rather than an irreparable deficiency in moral character

BACKGROUND Electrocardiographic presentations of left ventricle aneurysms are diverse; however, a persistent ST segment elevation post myocardial infarction is most commonly reported. CASE REPORT The authors present a case of a 67-year-old man who presented to the emergency department after three days of chest pain and was found to have an acute myocardial infarction with an incidental finding of a left ventricular aneurysm. His surface electrocardiogram, however, demonstrated only inverted T waves in the precordial leads. He had a very elevated serum troponin I consistent with an acute myocardial injury which prompted a cardiac catheterization with angioplasty. Post angioplasty, he had persistent T wave inversions in the precordial leads. CONCLUSIONS It is important for clinicians to appreciate that the presence of newly inverted T waves in patients with a late presentation post myocardial infarction should raise a concern for a possible left ventricular aneurysm.

Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression in differentiated hepatocytes, in particular, expression of SORT1, CELSR2, and PSRC1, consistent with previous analyses of this variant using other approaches. Initial investigation of additional SNPs also highlighted correlations with gene expression. These findings suggest that iPSC-based population studies hold promise as tools for the functional validation of GWAS variants.

INTRODUCTION: Psychiatric symptoms are reported to occur frequently in people living with HIV and may be associated with specific antiretrovirals. We analysed psychiatric symptoms observed with dolutegravir and other frequently prescribed anchor drugs. METHODS: Selected psychiatric symptoms (insomnia, anxiety, depression, and suicidality) occurring in HIV-positive patients during dolutegravir treatment across 5 randomized clinical trials (3 double-blind), in the Observational Pharmaco-Epidemiology Research & Analysis (OPERA(R)) cohort, and among cases spontaneously reported to ViiV Healthcare were analysed. RESULTS: In clinical trials, psychiatric symptoms were reported at low and similar rates in patients receiving dolutegravir or comparators (atazanavir, darunavir, efavirenz, or raltegravir). Insomnia was most commonly reported. The highest rates were observed in SINGLE (dolutegravir 17%, efavirenz 12%), with consistently lower rates in the other trials (dolutegravir: 3%-8% versus comparator: 3%-7%). More efavirenz-treated patients withdrew because of psychiatric symptoms than patients treated with other anchor drugs. In OPERA, history of psychiatric symptoms at baseline was lowest in efavirenz-treated patients compared with patients treated with dolutegravir, raltegravir, or darunavir. Despite baseline differences, prevalence and incidence during treatment were similar across the 4 anchor drugs. Withdrawal rates for psychiatric symptoms were lowest for dolutegravir (0%-0.6%) and highest for raltegravir (0%-2.5%). Spontaneously reported events were similar in nature to clinical trial data. CONCLUSIONS: Analysis of 3 different data sources shows that, similar to other frequently prescribed anchor drugs to treat HIV infection, psychiatric symptoms are also reported in DTG-treated patients. These events are reported with low frequency and rarely necessitate DTG discontinuation.