Faculty Bibliography

Smoking represents an important health risk for people living with HIV (PLHIV). Low adherence to smoking cessation pharmacotherapy may limit treatment effectiveness. In this study, 158 participants recruited from three HIV care centers in New York City were randomized to receive 12-weeks of varenicline (Chantix) either alone as standard care (SC) or in combination with text message (TM) support or TM plus cell phone-delivered adherence-focused motivational and behavioral therapy (ABT). Generalized linear mixed-effect models found a significant decline in varenicline adherence from week 1-12 across treatment groups. At 12-weeks, the probability of smoking abstinence was significantly higher in SC+TM+ABT than in SC. The study demonstrates the feasibility of delivering adherence-focused interventions to PLHIV who smoke. Findings suggest intensive behavioral support is an important component of an effective smoking cessation intervention for this population, and a focus on improving adherence self-efficacy may lead to more consistent adherence and higher smoking abstinence.

BACKGROUND: More than half of persons living with HIV (PLWH) in the United States are insufficiently engaged in HIV primary care and not taking antiretroviral therapy (ART), mainly African Americans/Blacks and Hispanics. In the proposed project, a potent and innovative research methodology, the multiphase optimization strategy (MOST), will be employed to develop a highly efficacious, efficient, scalable, and cost-effective intervention to increase engagement along the HIV care continuum. Whereas randomized controlled trials are valuable for evaluating the efficacy of multi-component interventions as a package, they are not designed to evaluate which specific components contribute to efficacy. MOST, a pioneering, engineering-inspired framework, addresses this problem through highly efficient randomized experimentation to assess the performance of individual intervention components and their interactions. We propose to use MOST to engineer an intervention to increase engagement along the HIV care continuum for African American/Black and Hispanic PLWH not well engaged in care and not taking ART. Further, the intervention will be optimized for cost-effectiveness. A similar set of multi-level factors impede both HIV care and ART initiation for African American/Black and Hispanic PLWH, primary among them individual- (e.g., substance use, distrust, fear), social- (e.g., stigma), and structural-level barriers (e.g., difficulties accessing ancillary services). Guided by a multi-level social cognitive theory, and using the motivational interviewing approach, the study will evaluate five distinct culturally based intervention components (i.e., counseling sessions, pre-adherence preparation, support groups, peer mentorship, and patient navigation), each designed to address a specific barrier to HIV care and ART initiation. These components are well-grounded in the empirical literature and were found acceptable, feasible, and promising with respect to efficacy in a preliminary study. METHODS/DESIGN: Study aims are: 1) using a highly efficient fractional factorial experimental design, identify which of five intervention components contribute meaningfully to improvement in HIV viral suppression, and secondary outcomes of ART adherence and engagement in HIV primary care; 2) identify mediators and moderators of intervention component efficacy; and 3) using a mathematical modeling approach, build the most cost-effective and efficient intervention package from the efficacious components. A heterogeneous sample of African American/Black and Hispanic PLWH (with respect to age, substance use, and sexual minority status) will be recruited with a proven hybrid sampling method using targeted sampling in community settings and peer recruitment (N = 512). DISCUSSION: This is the first study to apply the MOST framework in the field of HIV prevention and treatment. This innovative study will produce a culturally based HIV care continuum intervention for the nation's most vulnerable PLWH, optimized for cost-effectiveness, and with exceptional levels of efficacy, efficiency, and scalability. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02801747 , Registered June 8, 2016.

High levels of immune activation are reported for people who inject drugs (PWID). Studies of the relationship between injection behaviors and immune activation have yielded mixed results, in part due to lack of control for HCV in analyses. This study, of 48 HIV-seronegative PWID, examines this relationship controlling for HCV viremia. Frequency of injection was positively related to markers of immune activation (sCD14, %CD8+CD38+HLADR+T cells), as was duration of injection (hs-CRP and D-dimer). Sharing injection equipment was not related to markers studied. Findings suggest that efforts to encourage injection cessation or reduction in frequency can have positive health benefits through reducing immune activation.

BACKGROUND:Untreated, miliary tuberculosis (TB) has a mortality approaching 100%. As it is uncommon there is little specific data to guide its management. We report detailed data from a UK cohort of patients with miliary tuberculosis and the associations and predictive ability of admission blood tests with clinical outcomes. METHODS:Routinely collected demographic, clinical, blood, imaging, histopathological and microbiological data were assessed for all patients with miliary TB identified from the London TB register from 2008 to 2012 from Northwest London Hospitals NHS Trust. Multivariable logistic regression was used to assess factors independently associated with the need for critical care intervention. Receiver operator characteristics (ROC) were calculated to assess the discriminatory ability of admission blood tests to predict clinical outcomes. RESULTS:Fifty-two patients were identified with miliary tuberculosis, of whom 29% had confirmed central nervous system (CNS) involvement. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) or lumbar puncture for detecting CNS disease. Severe complications were frequent, with 15% requiring critical care intervention with mechanical ventilation. This was independently associated with admission hyponatraemia and elevated alanine aminotransferase (ALT). Having an admission sodium ≥125 mmol/L and an ALT <180 IU/L had 82% sensitivity and 100% specificity for predicting a favourable outcome with an area under the ROC curve (AUC) of 0.91. Despite the frequency of severe complications, one-year mortality was low at 2%. CONCLUSIONS:Although severe complications of miliary tuberculosis were frequent, mortality was low with timely access to critical care intervention, anti-tuberculous therapy and possibly corticosteroid use. Clinical outcomes could accurately be predicted using routinely collected biochemistry data.

Identifying undiagnosed HIV infection is necessary for the elimination of HIV transmission in the United States. The present study evaluated the efficacy of 3 community-based approaches for uncovering undiagnosed HIV among heterosexuals at high-risk (HHR), who are mainly African American/Black and Hispanic. Heterosexuals comprise 24% of newly reported HIV infections in the United States, but experience complex multilevel barriers to HIV testing. We recruited African American/Black and Hispanic HHR in a discrete urban area with both elevated HIV prevalence and poverty rates. Approaches tested were (1) respondent-driven sampling (RDS) and confidential HIV testing in 2 sessions (n = 3116); (2) RDS and anonymous HIV testing in one session (n = 498); and (3) venue-based sampling (VBS) and HIV testing in a single session (n = 403). The main outcome was newly diagnosed HIV infection. RDS with anonymous testing and one session reached HHR with less HIV testing experience and more risk factors than the other approaches. Furthermore, RDS with anonymous (4.0%) and confidential (1.0%) testing yielded significantly higher rates of newly diagnosed HIV than VBS (0.3%). Thus peer-referral approaches were more efficacious than VBS for uncovering HHR with undiagnosed HIV, particularly a single-session/anonymous strategy, and have a vital role to play in efforts to eliminate HIV transmission.

BACKGROUND: Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. OBJECTIVE: The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. METHODS: The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. RESULTS: The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (PrEP), conditional cash transfer (CCT), and contraceptives for females; and (4) referrals for HIV care among those identified as HIV-positive. The combination package platform selected is mobile health teams in an integrated services delivery model. A cross-sectional analysis will be conducted to determine the uptake of the interventions. To determine long-term impact, the protocol outlines enrolling selected participants in mutually exclusive longitudinal cohorts (HIV-positive, PrEP, CCT, and HIV-negative) followed by using mobile phone text messages (short message service, SMS) and in-person surveys to prospectively assess prevention method uptake, adherence, and risk compensation behaviors. Cross-sectional and sub-cohort analyses will be conducted to determine intervention packages uptake. CONCLUSIONS: The literature review, focus groups, and modeling indicate that offering age- and gender- specific combination HIV prevention interventions that include biomedical, behavioral, and structural interventions can have an impact on HIV risk reduction. Implementing this protocol will show the feasibility of delivering these services at scale. The MP3 Youth study is one of the few combination HIV prevention intervention protocols incorporating youth- and gender-specific interventions in one delivery setting. Lessons learned from the design of the protocol can be incorporated into the national guidance for combination HIV prevention for youth in Kenya and other high-burden SSA settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01571128; http://clinicaltrials.gov/ct2/show/NCT01571128?term=MP3+youth&rank=1 (Archived by WebCite at http://www.webcitation.org/6nmioPd54).

Runaway and homeless youth (RHY) are served by specialized settings (e.g., Drop-In Centers, Transitional Living Programs, and multi-program settings), but little is known about the characteristics of these organizations or their effects on RHY's behavioral and psychosocial outcomes. To address this gap we studied 29 randomly selected diverse settings across New York State, including those in rural, suburban, and urban areas. Within settings, we used the Youth Program Quality Assessment model to observe and rate programs for RHY (N=53), assess program administrators (N=30), and conduct anonymous structured assessment batteries with RHY aged 16-21 years (N =463). We found settings overall evidenced satisfactory-to-high quality on a multi perspective setting quality score. With respect to RHY's behavioral outcomes, engagement in school/job training/work was high (81%), substance use was moderate (mean use: 17 of the past 90 days), and 37% evidenced involvement in the street economy (e.g., drug dealing, burglary). RHY in Transitional Living Programs and multi-program settings had more engagement in school/job training/work and less involvement in the street economy than their peers in Drop-In Centers. The quality of settings was not associated with these three behavioral outcomes (school/training/work, substance use, street economy), likely due to issues of restricted range. However, higher setting quality was associated with four constructive psychosocial outcomes; namely, RHY's perceptions that settings foster positive outcomes in these three domains, and perceived resilience. Thus the present study highlights settings' overall good quality, with some variability, and provides guidance on strategies to assess setting quality. Consistent with the existing literature, RHY in Drop-In Centers are highly vulnerable and may require additional types of services/programs to achieve their potential. Further, while the present study suggests all settings benefit RHY, better quality settings may be able to move beyond meeting RHY's basic requirements and address higher order relational, psychosocial, and motivational needs. Importantly, fostering a sense of resilience among RHY, as well as young people's experiences of settings as helpful to them in achieving good behavioral outcomes, may have long-term beneficial effects on RHY's engagement in other settings, relationships, adaptation, and functioning. (C) 2017 Elsevier Ltd. All rights reserved.

BACKGROUND: Ecstasy (MDMA) use has regained popularity in the United States, particularly in the form of "Molly," which is often marketed as pure MDMA. Surveys have generally not included "Molly" in the definition of ecstasy, so rates of use may be underestimated. As popularity of ecstasy increases, research is needed to examine use among those at highest risk for use-nightlife attendees. METHODS: We surveyed 679 young adults (age 18-25) entering nightclubs and festivals holding electronic dance music (EDM) parties in New York City in 2015. A variation of time-space sampling was utilized. We examined prevalence and correlates of self-reported lifetime ecstasy use. RESULTS: Self-reported lifetime ecstasy use was common (42.8%, 95% CI: 32.8, 52.7). Use was most common among older participants, frequent party attendees, and those reporting higher levels of exposure to users. Those surveyed outside of festivals were less likely to report use compared to those surveyed outside of nightclubs (AOR = 0.37, p = .015). Over a third of ecstasy users (36.8%)reported use in pill, powder, and crystal form. Ecstasy users were also more likely to report use of other drugs, including novel psychoactive substances (e.g., 2C series drugs, synthetic cathinones ["bath salts"]). Half (50.4%) reported suspecting (21.9%) or finding out (28.5%) that their ecstasy had ever contained a drug other than MDMA. CONCLUSION: A large percentage of nightlife attendees in NYC report lifetime ecstasy use. Findings should inform prevention and harm reduction programming. Further research is needed as ecstasy continues to change (e.g., in form, purity, and name).

BACKGROUND: African American/Black and Hispanic persons living with HIV (AABH-PLWH) are under-represented in AIDS clinical trials (ACTs) in the United States. Barriers AABH-PLWH experience to ACTs are multi-faceted, including distrust of medical research, low levels of knowledge, unsupportive social norms, lack of referral, and challenges navigating ACT systems. In past research we found a multi-component peer-driven intervention was efficacious in boosting rates of screening for/enrollment into ACTs. The present qualitative study seeks to understand AABH-PLWH's perspectives on which specific intervention features or components had utility. Interventions features explored included structural elements (e.g., small group sessions, individual sessions on the ACT research unit); approaches (e.g., Motivational Interviewing); and specific components (e.g., small-group discussion of historical and cultural factors reducing participation among AABH-PLWH). METHODS: A total of 37 AABH-PLWH (mean age 50.6 years, SD=7.5 years; 48.6% female; 62.2% African American/Black, 27.0% Hispanic) were purposively selected from a larger study for in-depth interviews, which were audio-recorded, transcribed verbatim, and analyzed using systematic content analysis. RESULTS: We found the intervention improved knowledge and positive attitudes toward ACTs, and triggered social-level facilitators such as altruism and more positive social norms. Discussions of cultural/historical barriers to ACTs associated with race/ethnicity had utility. Holding a session on the ACT research unit reduced fear and increased motivation. Results highlighted the value of Motivational Interviewing, and several components were perceived as less useful (e.g., involving social network members in ACT decisions). CONCLUSION: Findings can inform future intervention designs to address racial/ethnic disparities in ACTs and have implications for trials of other conditions where racial/ethnic disparities persist.