Faculty Bibliography

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).

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.

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: 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).

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: Almost half of adult men in Vietnam are current cigarette smokers. Recent surveys also suggest a high prevalence of water pipe use, particularly in rural areas. Yet services to treat tobacco dependence are not readily available. The purpose of this study was to characterize current tobacco use treatment patterns among Vietnamese health care providers and factors influencing adherence to recommended guidelines for tobacco use screening and cessation interventions for water pipe, cigarette and dual users. METHODS: We conducted cross sectional surveys of 929 male current tobacco users immediately after they completed a primary care visit at one of 18 community health centers. RESULTS: Thirty-four percent of smokers used cigarettes only, 24% water pipe only, and 42% were dual users. Overall 12% of patients reported that a provider asked them if they used tobacco products during the visit. Providers were significantly more likely to screen cigarette smokers compared with water pipe or dual users (16%, 9% and 11% respectively). Similarly, 9% of current cigarette smokers received advice to quit compared to 6% of water pipe and 5% of dual users. No patients reported that their health care provider offered them assistance to quit (e.g., self-help materials, referral). CONCLUSION: Despite ratifying the Framework Convention on Tobacco Control, Vietnam has not made progress in implementing policies and systems to ensure smokers are receiving evidence-based treatment. High rates of water pipe and dual use indicate a need for health care provider training and policy changes to facilitate treatment for both cigarette and water pipe use.

OBJECTIVE: Trauma processing is central to healthy recovery, but few studies examine how youth process experiences of child sexual abuse (CSA). The current study builds on our prior work identifying individual differences in CSA processing strategies (i.e., Constructive, Absorbed, Avoidant) to examine whether abuse stigmatization, PTSD symptoms, and negative reactions from others experienced during the year after abuse discovery were associated with subsequent CSA processing strategies. METHOD: Participants included 160 ethnically diverse youth (8-15 years, 73% female) with confirmed cases of CSA. Predictors were measured at abuse discovery (T1) and 1 year later (T2). Individual differences in CSA processing strategies were assessed 6 years after discovery (T3) from participants' abuse narratives. RESULTS: The persistence of abuse stigmatization from T1 to T2 significantly increased the odds of using either an Avoidant or Absorbed (vs. Constructive) strategy at T3. Higher levels of PTSD symptoms at T1 as well as their persistence from T1 to T2 each significantly increased the odds of having an Absorbed versus Constructive strategy. The persistence of perceived negative reactions from others from T1 to T2 increased the odds of an Absorbed versus Avoidant strategy. Effect sizes ranged from medium to large (M d = 0.636). CONCLUSIONS: Results further validate prior work identifying distinct CSA processing strategies and suggest the persistence of abuse-specific disruptions over the year after abuse discovery may be associated with subsequent problems processing CSA experiences.

Background: Persistent immune activation is associated with a variety of adverse clinical outcomes. People who inject drugs (PWID) have high levels of immune activation in blood and mucosal tissues; however, the relative contributions of chronic HCV infection, highly prevalent among PWIDs, and the non-sterile injection of illicit drugs have remained obscure. Methods: We recruited (N=48 for each group): 1) active injectors of heroin 2) individuals who ceased injecting heroin for 1-2 months 3) individuals who ceased injecting heroin for 3-4 months 4) healthy non-injecting volunteers. Soluble (including sCD14, hs-CRP, TNF-a, IFN-g, IL-10, MIP-1a) and cell associated (CD38+HLA-DR+ CD4 and CD8+ T cells) markers of immune activation were quantified. Mixed-effects regression models with random intercepts to account for participation in more than one group were used to compare groups on markers of immune activation. Results: Participant characteristics are shown in Table 1 below. Levels of IL-12p70, IL-15, IL-1b, IL-2, IL-4, and IL-6 determined by multiplex ELISA were at or below the level of detection in 50% or more of the active injectors and were not analyzed. Mean levels of selected markers of systemic and cellular immune activation are shown in Table 2 below. Participants in Groups 2 and 3 had statistically significantly lower levels of TNF-a and % CD4+ and CD8+ CD38+/HLA-DR+ T cells compared to actively injecting Group 1 subjects only if HCV infection was spontaneously controlled or if subjects were HCV uninfected (HCV-aviremic). sCD14 levels in HCV-aviremic Group 3 subjects were significantly lower than in aviremic Group 1 subjects and comparable to Group 4. Additionally, hs-CRP levels were significantly lower in Group 2 but not in Group 3 compared to Group 1 subjects. In contrast, in HCV-viremic subjects, the above parameters were not significantly different between the groups and were significantly higher than in the healthy non-injecting volunteers. Levels of IFN-g, IL-10, and MIP-1a were comparable across Groups 1, 2, and 3 independent of the presence/absence of viremia. Conclusions: Active IDU and HCV viremia are associated with persistent immune activation. Select markers of immune activation are significantly lower among the HCV-aviremic who cease injecting but not in those who are HCV viremic. These findings may have public health consequences. Aggressive treatment of HCV infection as well as enhanced harm reduction efforts should converge to optimize long-term outcomes. (Table Presented)