Laurie Sylla

Lack of Reduction in Buprenorphine Injection After Introduction of Co-Formulated Buprenorphine/Naloxone to the Malaysian Market

Background: Diversion of buprenorphine (BPN) has been described in settings where it is legally prescribed and has resulted in increasing concern. To address this concern, co-formulation of buprenorphine/naloxone (BPN/NLX) replaced buprenorphine alone in Malaysia in December 2006. Methods: To assess the significance of BPN/NLX introduction, 41 BPN/NLX injectors in Kuala Lumpur, Malaysia were recruited using a modified snowball recruitment technique. Results: In January 2007, all subjects had previously injected BPN alone. During the transition from injecting BPN alone to co-formulated BPN/NLX, the mean daily BPN injection dose increased from 1.88 mg (range 1.0–4.0 mg) to 2.49 mg/day (p < .001). Overall, 18 (44%) subjects increased their daily amount of injection while 22 (54%) had no change in dose; only one subject reduced the amount of injection. Development of opioid withdrawal symptoms was the primary outcome, however the only symptom that was significantly associated with BPN/NLX dosage was the report of “stomach pains” (p = .01). In logistic regression analysis, the development of opioid withdrawal symptoms was associated with increased benzodiazepine injection and increased syringe sharing. Conclusion and Scientific Significance: These data suggests that the introduction of BPN/NLX did not reduce injection related risk behaviors such as syringe sharing and was associated with increased benzodiazepine use. Evidence-based approaches to treat BPN injection are urgently needed.

A prospective controlled trial of routine opt-out HIV testing in a men's jail.

Background Approximately 10 million Americans enter jails annually. The Centers for Disease Control and Prevention now recommends routine opt-out HIV testing in these settings. The logistics for performing routine opt-out HIV testing within jails, however, remain controversial. The objective of this study was to evaluate the optimal time to routinely HIV test newly incarcerated jail detainees using an opt-out strategy. Methods This prospective, controlled trial of routine opt-out HIV testing was conducted among 298 newly incarcerated male inmates in an urban mens jail in New Haven, Connecticut. 298 sequential entrants to the mens jail over a three week period in March and April 2008 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 103), early (next day, n = 98), or delayed (7 days, n = 97). The primary outcome was the proportion of men in each group consenting to testing. Results Routine opt-out HIV testing was significantly higher for the early (53%: AOR = 2.6; 95% CI = 1.5 to 4.7) and immediate (45%: AOR = 2.3; 95% CI = 1.3 to 4.0) testing groups compared to the delayed (33%) testing group. The immediate and early testing groups, however, did not significantly differ (p = 0.67). In multivariate analyses, factors significantly associated with routine opt-out HIV testing were assignment to the ‘early’ testing group (p = 0.0003) and low (bond ≥

Microbicide Acceptability Among High-Risk Urban U.S. Women: Experiences and Perceptions of Sexually Transmitted HIV Prevention

5,000, immigration or federal charges or pre-sentencing >30 days) likelihood of early release (p = 0.04). Two subjects received preliminary positive results and one of them was subsequently confirmed HIV seropositive. Conclusions In this mens jail where attrition was high, routine opt-out HIV testing was not only feasible, but resulted in the highest rates of HIV testing when performed within 24 hours of incarceration. Trial Registration ClinicalTrials.gov NCT00624247

Routine opt-out HIV testing strategies in a female jail setting: a prospective controlled trial.

Objectives: The objectives of this study were to measure microbicide acceptability among high-risk women in Hartford, Connecticut, and contextual factors likely to affect acceptability and use. Goal: The goal of this study was to assess usefulness of microbicides for HIV/sexually transmitted infection (STI) prevention for high-risk women. Study: Ethnographic interviews (n = 75) and a survey (n = 471) explored women’s perspectives on HIV/STI prevention, vaginal contraceptives similar to microbicides, and microbicide acceptability. Participants (n = 94) in a 2-week behavioral trial used an over-the-counter vaginal moisturizer to simulate microbicide use during sex with primary, casual, and/or paying partners. Results: Findings showed limited experience with vaginal contraceptives, but high interest in microbicides as an alternative to condoms, indicated by an acceptability index score of 2.73 (standard deviation, 0.49; scale of 1–4) in the overall sample. General microbicide acceptability varied by ethnicity, prior contraceptive and violence/abuse experiences, relationship power, and other attitudinal factors. The simulation trial indicated significant willingness to use the product in various locations and with all types of partners. Conclusions: Vaginal microbicides may improve prevention outcomes for high-risk inner-city women.

Multilevel Social Influences on Female Condom Use and Adoption Among Women in the Urban United States

Background Ten million Americans enter jails annually. The objective was to evaluate new CDC guidelines for routine opt-out HIV testing and examine the optimal time to implement routine opt-out HIV testing among newly incarcerated jail detainees. Methods This prospective, controlled trial of routine opt-out HIV testing was conducted among 323 newly incarcerated female inmates in Connecticuts only womens jail. 323 sequential entrants to the womens jail over a five week period in August and September 2007 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 108), early (next day, n = 108), or delayed (7 days, n = 107). The primary outcome was the proportion of women in each group consenting to testing. Results Routine opt-out HIV testing was significantly highest (73%) among the early testing group compared to 55% for immediate and 50% for 7 days post-entry groups. Other factors significantly (p = 0.01) associated with being HIV tested were younger age and low likelihood of early release from jail based on bond value or type of charge for which women were arrested. Conclusions In this correctional facility, routine opt-out HIV testing in a jail setting was feasible, with highest rates of testing if performed the day after incarceration. Lower testing rates were seen with immediate testing, where there is a high prevalence of inability or unwillingness to test, and with delayed testing, where attrition from jail increases with each passing day. Trial Registration ClinicalTrials.gov NCT00624247

Case series of buprenorphine injectors in Kuala Lumpur, Malaysia.

Heterosexually transmitted HIV remains of critical concern in the United States and around the world, especially among vulnerable and disadvantaged women, complicated by socioeconomic circumstances, gender power, addiction, and experiences of abuse, among other conditions. Effective woman-initiated HIV prevention options, such as the female condom (FC), are needed that women can use in different sexual relationship contexts. We conducted a behavioral and attitudinal survey with 461 primarily African American and Latina (especially Puerto Rican) women in Hartford, Connecticut, to measure factors on the individual, partner relationship, peer, and community levels influencing their initial and continued use of FC (using the prototype FC1) for disease prevention. We used multivariate analyses and structural equation modeling to assess effects of multiple level factors on FC use and unprotected sex with primary, casual, and paying partners. Initial, recent, and continued FC use was associated with factors on the individual level (education, marital status, drug use, child abuse experiences, HIV status), partner level (number of sex partners, paying sex partner, relationship power), and peer level (more or influential peers saying positive things about FC). Community level factors of availability and support were consistently poor across all sectors, which limited overall FC use. Patterns differed between African American and Latina women in stages and contexts of FC use and unprotected sex. FC can make a valuable contribution to reducing heterosexually transmitted HIV among women in many circumstances. The greatest barrier to increased FC use is the lack of a supportive community environment for its promotion and use.

Policy implications of integrating buprenorphine/naloxone treatment and HIV care

Diversion of buprenorphine has been described in settings where it is legally prescribed and has become an increasing concern in Malaysia; it resulted in banning of buprenorphine in Singapore where unsubstantiated case reports suggested that buprenorphine injection was associated with particularly poor outcomes. We therefore conducted a case series of qualitative interviews with buprenorphine injectors in Kuala Lumpur, Malaysia to examine further the issues surrounding buprenorphine injection as well as the abuse of midazolam in combination with buprenorphine. Interviews with 19 men do not suggest significant adverse health consequences from buprenorphine injection alone and injectors have adapted diverted buprenorphine as a treatment modality. A subset of these injectors, however, combined buprenorphine and midazolam for euphoric effects with resultant symptoms of a possible pharmacological interaction. Prospective cohort studies, rather than hospital-derived samples, are needed to better understand the safety of buprenorphine injection.

'Well, it's the risk of the unknown⋯ right?': A qualitative study of perceived risks and benefits of HIV cure research in the United States

Researchers, practitioners, and policymakers have long recognized the potential benefits of providing integrated substance abuse and medical care services, particularly for special populations such as people living with HIV/AIDS. Buprenorphine, an office-based pharmacological treatment for opioid dependence, offers new opportunities for integrating drug treatment into HIV care settings. However, the historical separation between the drug treatment and medical care systems has resulted in a host of policy barriers. The Buprenorphine and HIV Care Evaluation and Support initiative, a multisite demonstration project to assess the feasibility and effectiveness of integrating buprenorphine/naloxone into HIV care settings, provided an opportunity to evaluate if and how policy barriers affect efforts to integrate HIV care and addiction treatment. We found that financing issues, workforce and training issues, and the operational consequences of some conceptual differences between HIV care and addiction treatment are barriers to the full integration of buprenorphine into HIV care. We recommend changes to financing and reimbursement policies, programs to strengthen the addiction treatment skills of physicians, and cross training between the fields of addiction, medicine, drug treatment, and HIV medicine. By addressing some of the policy barriers to integration, this promising new treatment can help the thousands of people living with HIV/AIDS who are also opioid dependent.

Perceptions of Equipoise, Risk–Benefit Ratios, and “Otherwise Healthy Volunteers” in the Context of Early-Phase HIV Cure Research in the United States: A Qualitative Inquiry

Introduction Biomedical research towards an HIV cure is advancing in the United States and elsewhere, yet little is known about perceptions of risks and benefits among potential study participants and other stakeholders. We conducted a qualitative study to explore perceived risks and benefits of investigational HIV cure research among people living with HIV (PLWHIV), biomedical HIV cure researchers, policy-makers and bioethicists. Methods We conducted a qualitative research study using in-depth interviews with a purposive sample of PLWHIV, biomedical HIV cure researchers, policy-makers and bioethicists in 2015–2016. We analysed interview transcripts using thematic analysis anchored in grounded theory. Results We conducted and analyzed 36 key informant interviews. Qualitative analysis revealed four main findings. 1) Potential HIV cure study volunteers noted needing more information and education about the potential risks of HIV cure research. 2) Biomedical HIV cure researchers, policy-makers and bioethicists showed less awareness of social and financial risks of HIV cure research than PLWHIV. 3) Most respondents across the different categories of informants identified some risks that were too great to be acceptable in HIV cure research, although a subset of PLWHIV did not place an upper limit on acceptable risk. 4) PLWHIV showed a better awareness of potential psychological benefits of participating in HIV cure research than other groups of stakeholders. Conclusion Our research suggests that PLWHIV have a variable understanding of the individual risks, sometimes substantial, associated with participating in biomedical HIV cure research studies. Community engagement and increased research literacy may help improve community understanding. Intensive informed consent procedures will be necessary for ethical study implementation. The current state of HIV cure research offers greater potential benefits to society than to participants. There is likely to be disagreement among regulators, researchers, clinicians, and potential participants about what constitutes acceptable risk for HIV cure studies.

Research on HIV cure: Mapping the ethics landscape

Early-phase HIV cure research is conducted against a background of highly effective antiretroviral therapy, and involves risky interventions in individuals who enjoy an almost normal life expectancy. To explore perceptions of three ethical topics in the context of HIV cure research—(a) equipoise, (b) risk–benefit ratios, and (c) “otherwise healthy volunteers”—we conducted 36 in-depth interviews (IDIs) with three groups of purposively selected key informants: clinician-researchers (n = 11), policy-makers and bioethicists (n = 13), and people living with HIV (PLWHIV; n = 12). Our analysis revealed variability in perceptions of equipoise. Second, most key informants believed there was no clear measure of risk–benefit ratios in HIV cure research, due in part to the complexity of weighing (sometimes unknown) risks to participants and (sometimes speculative) benefits to science and society. Third, most clinician-researchers and policy-makers/bioethicists viewed potential HIV cure study participants as “otherwise healthy volunteers,” but this perception was not shared among PLWHIV in our study.