56 results on '"Springer SA"'
Search Results
2. Underuse of Lifesaving Medications for Opioid Use Disorder in US Jails.
- Author
-
Springer SA
- Subjects
- Humans, United States, Male, Adult, Female, Analgesics, Opioid therapeutic use, Middle Aged, Jails statistics & numerical data, Prisoners statistics & numerical data, Opiate Substitution Treatment statistics & numerical data, Opioid-Related Disorders drug therapy
- Published
- 2024
- Full Text
- View/download PDF
3. Missed Opportunities for Preexposure Prophylaxis Initiation in Hospitalized Persons With Opioid Use Disorder and Infectious Diseases.
- Author
-
Parchinski K, Neirinckx V, Frank C, Di Paola A, Tarfa A, Shenoi S, Vander Wyk B, Roth P, Ghantous T, Wegman MK, Strong M, Levin FR, Brady K, Nunes E, Litwin AH, and Springer SA
- Abstract
Hospitalizations are increasing among persons who use opioids, secondary to overdose and infections. Our study identified acute hospitalization as a reachable moment for engaging people who use drugs in increased screening and education about human immunodeficiency virus risk and prevention (preexposure prophylaxis)., Competing Interests: Potential conflicts of interest. S. A. S. has provided paid scientific consultation to Alkermes Inc and has received in-kind study drug donations from Alkermes Inc and Indivior Pharmaceutical Company for National Institutes of Health (NIH)–funded research. Sublocade was donated in-kind by Indivior Inc after an investigator-initiated application was approved. F. R. L. receives grant support from the NIDA, NCATS, Substance Abuse and Mental Health Services Administration, US World Meds; receives research support from Aelis Pharmaceuticals; receives medication from Indivior for research; receives royalties from APA Publishing; served as an unpaid member of a scientific advisory board for Alkermes, Indivior, Novartis, Teva, and US WorldMeds; and is a consultant to Major League Baseball. S. S.’s spouse worked for Merck pharmaceuticals from 1997 to 2007 and retains company stock in his retirement account. There is no conflict of interest, but it is included in the interest of full disclosure. K. B. receives grant support from NIDA, NCATS, and the Duke Foundation. A. H. L. has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. E. N. has served as an investigator on NIH-funded studies that received donated medication or digital therapeutics from Alkermes, Braeburn, Camurus, Indivior, Chess Health, and Pear Therapeutics, and has served as a consultant without compensation to Alkermes, Camurus, Indivior, and Pear Therapeutics. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2024
- Full Text
- View/download PDF
4. Serious Opioid Injection-Related Infection and Initiation of Medication for Opioid Use Disorder.
- Author
-
Springer SA
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Substance Abuse, Intravenous complications, Opioid-Related Disorders drug therapy, Analgesics, Opioid therapeutic use, Analgesics, Opioid adverse effects
- Published
- 2024
- Full Text
- View/download PDF
5. HIV Risk and Interest in Preexposure Prophylaxis in Justice-Involved Persons.
- Author
-
Nijhawan AE, Pulitzer Z, Torres B, Noreen N, Schultheis A, Frank C, Colon R, Brooks R, Proffitt R, Pankow J, Bennett A, Salyards M, Kuo I, Knight K, and Springer SA
- Subjects
- Female, Humans, Male, Hispanic or Latino, Homosexuality, Male, Risk Factors, United States, White, Black or African American, HIV Infections epidemiology, HIV Infections prevention & control, Pre-Exposure Prophylaxis
- Abstract
Preexposure prophylaxis (PrEP) is underused in persons who use drugs and justice-involved persons. In an ongoing randomized controlled trial in 4 US locations comparing patient navigation versus mobile health unit on time to initiation of HIV medication or PrEP for justice-involved persons who use stimulants or opioids and who are at risk for or living with HIV, we assessed HIV risk factors, perceived HIV risk, and interest in PrEP. Participants without HIV (n = 195) were 77% men, 65% White, 23% Black, and 26% Hispanic; 73% reported a recent history of condomless sex, mainly with partners of unknown HIV status. Of 34% (67/195) reporting injection drug use, 43% reported sharing equipment. Despite risk factors, many persons reported their risk for acquiring HIV as low (47%) or no (43%) risk, although 51/93 (55%) with PrEP indications reported interest in PrEP. Justice-involved persons who use drugs underestimated their HIV risk and might benefit from increased PrEP education efforts.
- Published
- 2024
- Full Text
- View/download PDF
6. Editorial: Glycans: molecules at the interface of immunity and disease.
- Author
-
Springer SA and Siddiqui SS
- Subjects
- Polysaccharides, Lectins
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2024
- Full Text
- View/download PDF
7. Ending the HIV Epidemic for Persons Who Use Drugs: the Practical Challenges of Meeting People Where They Are.
- Author
-
Springer SA
- Subjects
- Humans, HIV Infections drug therapy, HIV Infections epidemiology, HIV Infections prevention & control, Epidemics prevention & control
- Published
- 2023
- Full Text
- View/download PDF
8. Validation of Two Diagnostic Assessments for Opioid and Stimulant Use Disorder for Use by Non-Clinicians.
- Author
-
Di Paola A, Farabee D, and Springer SA
- Abstract
Objective: The United States is in the fourth wave of the opioid epidemic marked by the increase in fentanyl and co-occurring stimulant use related overdose deaths. Measures are needed to quickly diagnose opioid and stimulant use disorders, yet current traditional diagnostic assessments pose barriers to providing rapid diagnoses., Methods: This study aimed to (1) validate an updated version of the Rapid Opioid Dependence Screen (RODS) from DSM-IV criteria for opioid dependence to the now DSM-5 moderate-to-severe opioid use disorder, the Rapid Opioid Use Disorder Assessment (ROUDA); and (2) create and validate the Rapid Stimulant Use Disorder Assessment to DSM-5 stimulant use disorder (RSUDA) when compared to the substance use disorder module from the DSM-5 version of the Mini International Neuropsychiatric Interview., Results: One-hundred and fifty adults completed study assessments, 122 reported opioid misuse and 140 reported stimulant misuse within their lifetime. The ROUDA had a sensitivity of 82.5% (95% confidence interval [CI] 75.7, 89.2), specificity of 100.0% (95% CI: 100, 100), and strong internal consistency α = 0.94. The RSUDA had similarly high sensitivity (83.8%, 95% CI: 77.7, 89.9), specificity (91.4%, 95% CI: 86.8, 96.1), and internal consistency α = 0.87. The ROUDA and RSUDA are efficient and valid measures that can be administered in various settings by non-clinical staff to rapidly diagnose opioid and stimulant use disorders and allow for immediate treatment and harm reduction interventions., Conclusions: The ROUDA and RSUDA are efficient and valid measures that can be administered by non-clinicians to rapidly diagnose opioid and stimulant use disorders., (© 2023 The Authors. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.)
- Published
- 2023
- Full Text
- View/download PDF
9. The relationship between reincarceration and treatment of opioid use disorder with extended-release naltrexone among persons with HIV.
- Author
-
Parchinski K, Di Paola A, Wilson AP, and Springer SA
- Abstract
Background: In the United States, a disproportionate number of persons with HIV (PWH) and opioid use disorder (OUD) are involved in the justice system. Medications for OUD (MOUD) can reduce convictions and incarceration time in persons with OUD. Extended-release naltrexone (XR-NTX) has been shown to reduce craving of opioids, recurrence of use, and overdose and help achieve or maintain HIV viral suppression in PWH with OUD involved with the justice system., Objectives: This retrospective study aimed to describe factors associated with reincarceration and to evaluate if XR-NTX was associated with reduced reincarceration among PWH and OUD who were released to the community from incarceration., Methods: Data from participants released to the community from incarceration from a completed randomized controlled trial was analyzed using a generalized linear model to estimate odds ratios associated with reincarceration and a Kaplan-Meier survival analysis to determine time to reincarceration and non-reincarcerated individuals were compared., Results: Of the 77 participants, 41 (53.2%) were reincarcerated during the 12-month study period. The mean time to reincarceration was 190 days (SD=108.3). Compared with participants who remained in the community, reincarcerated participants were more likely to have major depressive disorder at study baseline, increased opioid cravings, longer mean lifetime incarceration, and a higher physical quality of life score. XR-NTX was not significantly associated statistically with reincarceration in this analysis., Conclusion: Reducing reincarceration is a public health priority, given the high proportion of PWH and OUD in the U.S. justice system as well as high degrees of persons returning to the community and having care interrupted due to reincarceration. This analysis determined that potentially identifying depression in recently released individuals could improve HIV outcomes, decrease recurrence of opioid use, and reduce reincarceration., Competing Interests: Author Sandra Springer, MD has provided paid scientific consultation to Alkermes Inc. Sandra Springer, MD has received in-kind study drug donations from Alkermes Inc and Indivior Pharmaceutical Company for NIH-funded research. The authors alone are responsible for the content and writing of this paper.
- Published
- 2023
- Full Text
- View/download PDF
10. The impact of COVID-19 on the treatment of opioid use disorder in carceral facilities: a cross-sectional study.
- Author
-
Saunders EC, Satcher MF, Monico LB, McDonald RD, Springer SA, Farabee D, Gryczynski J, Nyaku A, Reeves D, Kunkel LE, Schultheis AM, Schwartz RP, Lee JD, Marsch LA, and Waddell EN
- Abstract
While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs. Naltrexone Opioid Treatments in Criminal Justice System-Involved Adults (EXIT-CJS) study. In December 2020, carceral sites (n = 6; median pre-COVID 2020 monthly census = 3468 people) and CTPs (n = 7; median pre-COVID 2020 monthly census = 550 patients) participating in EXIT-CJS completed a cross-sectional web-based survey. The survey assessed changes pre- (January-March 2020) and post- (April-September 2020) COVID-19 in OUD treatment, telemedicine use, re-entry supports and referral practices. Compared to January-March 2020, half of carceral sites (n = 3) increased the total number of persons initiating medication for opioid use disorder (MOUD) from April-September 2020, while a third (n = 2) decreased the number of persons initiated. Most CTPs (n = 4) reported a decrease in the number of new admissions from April-September 2020, with two programs stopping or pausing MOUD programs due to COVID-19. All carceral sites with pre-COVID telemedicine use (n = 5) increased or maintained telemedicine use, and all CTPs providing MOUD (n = 6) increased telemedicine use. While expansion of telemedicine services supported MOUD service delivery, the majority of sites experienced challenges providing community support post-release, including referrals to housing, employment, and transportation services. During the COVID-19 pandemic, this small sample of carceral and CTP sites innovated to continue delivery of treatment for OUD. Expansion of telemedicine services was critical to support MOUD service delivery. Despite these innovations, sites experienced challenges providing reintegration supports for persons in the community. Pre-COVID strategies for identifying and engaging individuals while incarcerated may be less effective since the pandemic. In addition to expanding research on the most effective telemedicine practices for carceral settings, research exploring strategies to expand housing and employment support during reintegration are critical., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
11. Evaluation of the Impact of HIV Serostatus on the Hepatitis C Virus Care Cascade and Injection Drug Use Among Persons Initiating Medication Treatment for Opioid Use Disorder.
- Author
-
Lier AJ, Vander Wyk B, Di Paola A, and Springer SA
- Abstract
Background: Persons who inject drugs are at increased risk for acquiring hepatitis C virus (HCV). Medications for opioid use disorder (MOUD) are associated with reduced injection drug use (IDU) frequency among persons with opioid use disorder (OUD). However, whether HCV treatment uptake or changes in IDU frequency differ by HIV serostatus among persons receiving MOUD is incompletely understood., Methods: A secondary analysis was performed of data collected from 2 prospective cohort studies of participants with (PWH) or without HIV with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-diagnosed OUD who were initiated on methadone, buprenorphine, or naltrexone., Results: Of 129 participants, 78 (60.5%) were HCV antibody positive. PWH underwent increased HCV viral load testing (76.7% vs 43.3%; P = .028), but HCV treatment rates did not differ (17.6% vs 10.0%; P = .45) by HIV status. Participants without HIV reported a greater reduction in mean opioid IDU at 90 days (10.7 vs 2.0 fewer days out of 30; P < .001), but there were no group differences at 90 days. Stimulant use did not differ between groups. Urine opioid positivity declined from baseline to 90 days among the entire cohort (61.4% to 38.0%; P < .001) but did not differ by HIV serostatus., Conclusions: PWH who received MOUD underwent higher rates of follow-up HCV testing, but HCV treatment rates did not significantly differ by HIV serostatus. Participants without HIV on MOUD reported a greater reduction in opioid IDU. Improved integration of concomitant OUD with HCV and HIV screening, linkage to care, and treatment are needed for persons without HIV., Competing Interests: Potential conflicts of interest. Dr. Sandra Springer has provided scientific consultation with paid honoraria from Alkermes, Inc., and has received in-kind study donations of Vivitrol for NIDA-funded research and in-kind study donations of SUBLOCADE from Indivior for NCATS- and NIDA-funded research. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2022
- Full Text
- View/download PDF
12. Study protocol of a randomized controlled trial comparing two linkage models for HIV prevention and treatment in justice-involved persons.
- Author
-
Springer SA, Nijhawan AE, Knight K, Kuo I, Di Paola A, Schlossberg E, Frank CA, Sanchez M, Pankow J, Proffitt RP, Lehman W, Pulitzer Z, Thompson K, Violette S, and Harding KK
- Subjects
- Analgesics, Opioid therapeutic use, Anti-Retroviral Agents therapeutic use, Humans, Randomized Controlled Trials as Topic, Acquired Immunodeficiency Syndrome drug therapy, HIV Infections drug therapy, HIV Infections epidemiology, HIV Infections prevention & control, Hepatitis C drug therapy, Hepatitis C epidemiology, Hepatitis C prevention & control, Pre-Exposure Prophylaxis methods, Sexually Transmitted Diseases complications, Substance-Related Disorders complications
- Abstract
Background: Persons involved in the justice system are at high risk for HIV and drug overdose upon release to the community. This manuscript describes a randomized controlled trial of two evidence-based linkage interventions for provision of HIV prevention and treatment and substance use disorder (SUD) services in four high risk communities to assess which is more effective at addressing these needs upon reentry to the community from the justice system., Methods: This is a 5-year hybrid type 1 effectiveness-implementation randomized controlled trial that compares two models (Patient Navigation [PN] or Mobile Health Unit [MHU] service delivery) of linking justice-involved individuals to the continuum of community-based HIV and SUD prevention and treatment service cascades of care. A total of 864 justice-involved individuals in four US communities with pre-arrest histories of opioid and/or stimulant use who are living with or at-risk of HIV will be randomized to receive either: (a) PN, wherein patient navigators will link study participants to community-based service providers; or (b) services delivered via an MHU, wherein study participants will be provided integrated HIV prevention/ treatment services and SUD services. The six-month post-release intervention will focus on access to pre-exposure prophylaxis (PrEP) for those without HIV and antiretroviral treatment (ART) for people living with HIV (PLH). Secondary outcomes will examine the continuum of PrEP and HIV care, including: HIV viral load, PrEP/ ART adherence; HIV risk behaviors; HCV testing and linkage to treatment; and sexually transmitted infection incidence and treatment. Additionally, opioid and other substance use disorder diagnoses, prescription, receipt, and retention on medication for opioid use disorder; opioid and stimulant use; and overdose will also be assessed. Primary implementation outcomes include feasibility, acceptability, sustainability, and costs required to implement and sustain the approaches as well as to scale-up in additional communities., Discussion: Results from this project will help inform future methods of delivery of prevention, testing, and treatment of HIV, HCV, substance use disorders (particularly for opioids and stimulants), and sexually transmitted infections for justice-involved individuals in the community., Trial Registration: Clincialtrials.gov NCT05286879 March 18, 2022., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
13. Factors associated with retention on medications for opioid use disorder among a cohort of adults seeking treatment in the community.
- Author
-
Biondi BE, Vander Wyk B, Schlossberg EF, Shaw A, and Springer SA
- Subjects
- Adult, Analgesics, Opioid therapeutic use, Female, Humans, Male, Methadone therapeutic use, Naltrexone therapeutic use, Opiate Substitution Treatment, Pain drug therapy, Prospective Studies, Buprenorphine therapeutic use, Drug Overdose drug therapy, Opioid-Related Disorders drug therapy
- Abstract
Background: Medication treatment for opioid use disorder (OUD) (MOUD; buprenorphine and methadone) reduces opioid use and overdose. Discontinuation of MOUD can quickly lead to relapse, overdose and death. Few persons who initiate MOUD are retained on treatment, thus it is critical to identify factors associated with retention., Methods: Evaluated data was from an ongoing prospective cohort study of adults aged 18 or older with DSM-5 moderate to severe OUD seeking MOUD in the community and followed for 6 months. Participants were considered retained on MOUD through 6 months if they reported taking MOUD at every study interview without discontinuation. A high dose of MOUD was defined as a methadone dose > 85 mg or buprenorphine dose ≥ 16 mg. Multivariable logistic regression was conducted to assess factors associated with 6-month MOUD retention., Results: A total of 118 participants (73% male, 58% white, 36% with HIV) were included. Buprenorphine was initiated by 58% and 42% started methadone. MOUD retention was 49% and 58% among buprenorphine and methadone, respectively, at 6-months. In adjusted models, a high MOUD dose (OR = 4.71, 95% CI 2.05-10.84) and higher pain interference (OR = 1.59, 95% CI 1.15-2.19) was associated with MOUD retention., Conclusions: Adequate dosing of MOUD leads to improved retention on MOUD. Further, persons with high pain interference at baseline had higher odds of retention on MOUD. Both methadone and buprenorphine have analgesic effects, thus those with high pain interference could have dual benefits of MOUD for treating OUD and pain. Interventions should be tailored to improve adequate MOUD dosing to improve retention on MOUD., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
14. Rationale, design and methods of VA-BRAVE: a randomized comparative effectiveness trial of two formulations of buprenorphine for treatment of opioid use disorder in veterans.
- Author
-
Petrakis I, Springer SA, Davis C, Ralevski E, Gu L, Lew R, Hermos J, Nuite M, Gordon AJ, Kosten TR, Nunes EV, Rosenheck R, Saxon AJ, Swift R, Goldberg A, Ringer R, and Ferguson R
- Subjects
- Humans, Narcotic Antagonists therapeutic use, SARS-CoV-2, Buprenorphine therapeutic use, COVID-19, Opioid-Related Disorders drug therapy, Veterans
- Abstract
Background: To address the US opioid epidemic, there is an urgent clinical need to provide persons with opioid use disorder (OUD) with effective medication treatments for OUD (MOUD). Formulations of sublingual buprenorphine/naloxone (SL-BUP/NLX) are considered the standard of care for OUD including within the Veterans Healthcare Administration (VHA). However, poor retention on MOUD undermines its effectiveness. Long-acting injectable monthly buprenorphine (INJ-BUP) (e.g., Sublocade®) has the potential to improve retention and therefore reduce opioid use and overdose. Designing and conducting studies for OUD pose unique challenges. The strategies and solutions to some of these considerations in designing Cooperative Studies Program (CSP) 2014, Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE), a randomized, 20-site, clinical effectiveness trial comparing INJ-BUP to SL-BUP/NLX conducted within the VHA may provide valuable guidance for others confronted with similar investigation challenges., Methods: This 52-week, parallel group, open-label, randomized controlled trial (RCT) evaluates the comparative effectiveness of two current FDA-approved formulations of buprenorphine: (1) daily SL-BUP/NLX vs. (2) monthly (28-day) INJ-BUP for Veterans with moderate to severe OUD (n = 952). The primary outcomes are (1) retention in MOUD and (2) opioid abstinence. Secondary outcomes include measures of other drug use, psychiatric symptoms, medical outcomes including prevalence rates of HIV, hepatitis B and C as well as social outcomes (housing instability, criminal justice involvement), service utilization and cost-effectiveness. Special considerations in conducting a comparative effectiveness trial with this population and during COVID-19 pandemic were also included., Discussion: The evaluation of the extended-release formulation of buprenorphine compared to the standard sublingual formulation in real-world VHA settings is of paramount importance in addressing the opioid epidemic. The extent to which this new treatment facilitates retention, decreases opioid use, and prevents severe sequelae of OUD has not been studied in any long-term trial to date. Positive findings in this trial could lead to widespread adoption of MOUD, and, if proven superior INJ-BUP, by clinicians throughout the VHA and beyond. This treatment has the potential to reduce opioid use among Veterans, improve medical, psychological, and social outcomes, and save lives at justifiable cost. Trial registration Registered at Clinicaltrials.gov NCT04375033., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
15. Design and implementation of a cohort study of persons living with HIV infection who are initiating medication treatment for opioid use disorder to evaluate HIV-1 persistence.
- Author
-
Schultheis A, Sanchez M, Pedersen S, Kyriakides T, Ho YC, Kluger Y, and Springer SA
- Abstract
Background: Opioid use disorder (OUD) negatively impacts the HIV continuum of care for persons living with HIV (PLH). Medication treatment for OUD (MOUD) may have differential biological effects in individuals with HIV and OUD. To understand the role of MOUD - opioid agonist methadone, partial agonist buprenorphine and antagonist naltrexone - in HIV-1 persistence and reactivation, we will use molecular virology approaches to carry out the first prospective, longitudinal studies of adults living with HIV with OUD initiating MOUD. One of the major challenges to studying the impact of MOUD on HIV persistence is the low retention rate of study participants and the requirement of large-volume blood sampling to study the HIV proviral landscape and expression profiles., Methods: A prospective cohort study is underway to study the HIV-1 expression, proviral landscape, and clonal expansion dynamics using limited blood sampling from persons with DSM-5 diagnosed OUD who are living with HIV infection and initiating treatment with methadone, buprenorphine, or extended-release naltrexone., Results: We describe the recruitment, laboratory, and statistical methods of this study as well as the protocol details of this on-going study. Out of the 510 screened for enrollment into the study, 35 (7%) were eligible and 27 were enrolled thus far. Retention through month 3 has been high at 95%., Conclusions: This on-going study is evaluating the impact of MOUD on HIV persistence at the molecular virology level using limited blood sampling via a prospective, longitudinal study of people living with HIV DSM-5 OUD initiating treatment with MOUD., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Springer has received honoraria from Alkermes Inc and has received in-kind donations of extended-release naltrexone for prior and current NIH-sponsored trials ; and Indivior incorporated has provided in kind donations for Sublocade for this NIH-sponsored project., (Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
16. Feasibility of a community-based delivery model for HIV pre-exposure prophylaxis among bar patrons in rural South Africa.
- Author
-
Grammatico MA, Moll AP, Choi K, Springer SA, and Shenoi SV
- Subjects
- Adolescent, Adult, Feasibility Studies, Humans, Male, Medication Adherence, South Africa, Anti-HIV Agents therapeutic use, HIV Infections diagnosis, HIV Infections drug therapy, HIV Infections epidemiology, Pre-Exposure Prophylaxis
- Abstract
Introduction: South Africa, home to the world's largest HIV epidemic, has made great strides in improving access to HIV services, but specific groups, particularly young men, remain difficult to engage in the HIV care cascade. Alcohol use disorder, prevalent in South Africa, further complicates engagement. Congregate settings where alcohol is served, known as shebeens, are an ideal place to engage young people for HIV testing, treatment and prevention, including pre-exposure prophylaxis (PrEP). Here, we characterize the uptake of PrEP in shebeen patrons and explore the effect of alcohol consumption on PrEP uptake by piloting a community-based delivery model., Methods: In the rural Kwazulu-Natal province (KZN) of South Africa, a field team made up of all men offered screenings outside of shebeens at 27 events over 6 months in 2020. Screenings included rapid HIV testing and Alcohol Use Disorder Identification Test (AUDIT). Participants who tested negative for HIV were offered PrEP as once daily oral tenofovir disoproxil fumarate/emtricitabine. Short-term retention was determined. Logistic regression was performed to identify predictors of PrEP uptake, including unadjusted and adjusted odds ratios (OR) with 95% confidence interval., Results: One hundred and sixty-two shebeen patrons were screened, and 136 (84%) were eligible for PrEP. Among those eligible, 37 (27%) completed clinical evaluation and initiated PrEP. Among PrEP initiators, 91.9% were men, median age was 26.0 years (interquartile range 21-31), 32.4% were employed, 18.9% had running water and 70.3% had AUDIT scores indicating hazardous drinking. Among 37 initiators, 25 (68%) were retained at 1 month, and 19 (51%) were retained at 4 months. Independent predictors of PrEP uptake among all bar patrons, and only men (108 screened and 34 initiators), included younger age (OR 0.92 [0.88-0.97]) and lifetime number of sexual partners (OR 1.07 [1.02-1.13])., Conclusions: Community-based PrEP delivery after engagement at shebeens in rural South Africa is a feasible and novel approach to reach a traditionally difficult-to-engage population, particularly young men. In this small sample, sexual risk behaviours predicted PrEP uptake. Hazardous drinking was not a barrier to PrEP initiation., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)
- Published
- 2021
- Full Text
- View/download PDF
17. A Systematic Review and Meta-Analysis of Studies Evaluating the Effect of Medication Treatment for Opioid Use Disorder on Infectious Disease Outcomes.
- Author
-
McNamara KF, Biondi BE, Hernández-Ramírez RU, Taweh N, Grimshaw AA, and Springer SA
- Abstract
The opioid epidemic has fueled infectious disease epidemics. We determined the impact of medications for opioid use disorder (MOUD) on treatment outcomes of opioid use disorder (OUD)-associated infectious diseases: antiretroviral therapy (ART) adherence, human immunodeficiency virus (HIV) viral suppression, hepatitis C virus (HCV) sustained virologic response, HCV reinfection, new hepatitis B virus infections, and infectious endocarditis-related outcomes. Manuscripts reporting on these infectious disease outcomes in adults with OUD receiving MOUD compared with those with OUD "not" receiving MOUD were included. Initial search yielded 8169 papers; 9 were included in the final review. The meta-analysis revealed that MOUD was associated with greater ART adherence (odds ratio [OR] = 1.55; 95% confidence interval [CI] = 1.12-2.15) and HIV viral suppression (OR = 2.19; 95% CI = 1.88-2.56). One study suggested a positive association between MOUD and HCV sustained virologic response. There is significant support for integrating MOUD with HIV treatment to improve viral suppression among persons with HIV (PWH) and OUD. Treatment of OUD among PWH should be a priority to combat the opioid and HIV epidemics., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2021
- Full Text
- View/download PDF
18. Hepatitis C in the United States: One Step Forward, Two Steps Back.
- Author
-
Rio CD and Springer SA
- Subjects
- Humans, United States epidemiology, Hepacivirus, Hepatitis C epidemiology
- Published
- 2021
- Full Text
- View/download PDF
19. Transcriptome alterations are enriched for synapse-associated genes in the striatum of subjects with obsessive-compulsive disorder.
- Author
-
Piantadosi SC, McClain LL, Klei L, Wang J, Chamberlain BL, Springer SA, Lewis DA, Devlin B, and Ahmari SE
- Subjects
- Corpus Striatum, Gray Matter, Humans, Magnetic Resonance Imaging, Synapses, Obsessive-Compulsive Disorder genetics, Transcriptome
- Abstract
Obsessive-compulsive disorder (OCD) is a chronic and severe psychiatric disorder for which effective treatment options are limited. Structural and functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) and striatum in the pathophysiology of the disorder. Recent genetic evidence points to involvement of components of the excitatory synapse in the etiology of OCD. However, the transcriptional alterations that could link genetic risk to known structural and functional abnormalities remain mostly unknown. To assess potential transcriptional changes in the OFC and two striatal regions (caudate nucleus and nucleus accumbens) of OCD subjects relative to unaffected comparison subjects, we sequenced messenger RNA transcripts from these brain regions. In a joint analysis of all three regions, 904 transcripts were differentially expressed between 7 OCD versus 8 unaffected comparison subjects. Region-specific analyses highlighted a smaller number of differences, which concentrated in caudate and nucleus accumbens. Pathway analyses of the 904 differentially expressed transcripts showed enrichment for genes involved in synaptic signaling, with these synapse-associated genes displaying lower expression in OCD subjects relative to unaffected comparison subjects. Finally, we estimated that cell type fractions of medium spiny neurons were lower whereas vascular cells and astrocyte fractions were higher in tissue of OCD subjects. Together, these data provide the first unbiased examination of differentially expressed transcripts in both OFC and striatum of OCD subjects. These transcripts encoded synaptic proteins more often than expected by chance, and thus implicate the synapse as a vulnerable molecular compartment for OCD.
- Published
- 2021
- Full Text
- View/download PDF
20. Design and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder.
- Author
-
Biondi BE, Mohanty S, Wyk BV, Montgomery RR, Shaw AC, and Springer SA
- Abstract
Background: Opioid use disorder (OUD) negatively impacts the HIV continuum of care for persons living with HIV. Medication treatment for OUD (MOUD) may have differential biological effects in individuals with HIV and OUD. To address the question of modulation of immune responses by MOUDs, we describe state of the art systems biology approaches to carry out the first prospective, longitudinal study of persons with and without HIV infection with OUD initiating MOUD., Methods: A prospective cohort study of persons with DSM-5 diagnosed OUD who are living with and without HIV infection and initiating treatment with methadone or buprenorphine is underway to assess biological effects of these medications on immunobiological outcomes., Results: We describe the recruitment, laboratory, and statistical methods of this study as well as the protocol details. Of those screened for enrollment into the study, 468 (36%) were eligible and 135 were enrolled thus far. Retention through month 6 has been high at 80%., Conclusions: This study will use state of the art systems biology approaches to carry out the first prospective, longitudinal studies of persons living with and without HIV with DSM-5 OUD initiating treatment with MOUD., Competing Interests: The authors have no conflicts of interest to report related to this research.
- Published
- 2021
- Full Text
- View/download PDF
21. Hazardous alcohol use, antiretroviral therapy receipt, and viral suppression in people living with HIV who inject drugs in the United States, India, Russia, and Vietnam.
- Author
-
Wagman JA, Wynn A, Matsuzaki M, Gnatienko N, Metsch LR, Del Rio C, Feaster DJ, Nance RM, Whitney BM, Delaney JAC, Kahana SY, Crane HM, Chandler RK, Elliott JC, Altice F, Lucas GM, Mehta SH, Hirsch-Moverman Y, El-Sadr WM, Vu Q, Nguyen Thanh B, Springer SA, Tsui JI, and Samet JH
- Subjects
- Adult, Cross-Sectional Studies, Female, Humans, India epidemiology, Male, Middle Aged, Russia epidemiology, United States, Vietnam epidemiology, Viral Load, Alcohol-Related Disorders epidemiology, Alcohol-Related Disorders virology, Anti-Retroviral Agents administration & dosage, HIV Infections drug therapy, HIV Infections epidemiology, HIV Infections virology, Substance Abuse, Intravenous epidemiology, Substance Abuse, Intravenous virology
- Abstract
Objectives: In high-income countries, hazardous alcohol use is associated with reduced receipt of antiretroviral therapy (ART) and viral suppression among people living with HIV (PLHIV) who inject drugs. These associations are less understood in lower middle-income countries (LMIC) and upper middle-income countries., Design: We examined associations between hazardous alcohol use, ART receipt, and viral suppression among PLHIV who reported current or former injection drug use. Participants were from nine studies in the United States (high-income country), India (LMIC), Russia (upper middle-income country), and Vietnam (LMIC)., Methods: Hazardous alcohol use was measured via Alcohol Use Disorders Identification Test. Outcomes were HIV viral suppression (viral load of <1000 RNA copies/ml) and self-reported ART receipt. Logistic regression assessed associations between hazardous alcohol use and both outcome variables, controlling for age and sex, among participants with current and former injection drug use., Results: Among 2790 participants, 16% were women, mean age was 37.1 ± 9.5 years. Mean Alcohol Use Disorders Identification Test scores were 4.6 ± 8.1 (women) and 6.2 ± 8.3 (men); 42% reported ART receipt; 40% had viral suppression. Hazardous alcohol use was significantly associated with reduced ART receipt in India (adjusted odds ratio = 0.59, 95% confidence interval: 0.45-0.77, P < 0.001); and lower rates of viral suppression in Vietnam (adjusted odds ratio = 0.51, 95% confidence interval: 0.31-0.82, P = 0.006)., Conclusion: Associations between hazardous alcohol use, ART receipt, and viral suppression varied across settings and were strongest in LMICs. Addressing hazardous alcohol use holds promise for improving HIV continuum of care outcomes among PLHIV who inject drugs. Specific impact and intervention needs may differ by setting.
- Published
- 2020
- Full Text
- View/download PDF
22. Preventing HIV outbreaks among people who inject drugs in the United States: plus ça change, plus ça même chose.
- Author
-
Strathdee SA, Kuo I, El-Bassel N, Hodder S, Smith LR, and Springer SA
- Subjects
- Continuity of Patient Care, HIV Infections psychology, Humans, Pre-Exposure Prophylaxis, Substance Abuse, Intravenous epidemiology, United States epidemiology, Disease Outbreaks prevention & control, HIV Infections epidemiology, HIV Infections prevention & control, Substance Abuse, Intravenous complications, Substance Abuse, Intravenous psychology, Substance-Related Disorders psychology
- Abstract
: This editorial review covers current trends in the epidemiology of HIV among people who inject drugs (PWID) in the United States, including four recent HIV outbreaks. We discuss gaps in the prevention and treatment cascades for HIV and medications for opioid disorder and propose lessons learned to prevent future HIV outbreaks. Over the last decade, North America has been in the throes of a major opioid epidemic, due in part to over-prescribing of prescription opiates, followed by increasing availability of cheap heroin, synthetic opioids (e.g. fentanyl), and stimulants (e.g. methamphetamine). Historically, HIV infection among PWID in the US had predominantly affected communities who were older, urban and Black. More recently, the majority of these infections are among younger, rural or suburban and Caucasian PWID. All four HIV outbreaks were characterized by a high proportion of women who inject drugs and underlying socioeconomic drivers such as homelessness and poverty. We contend that the US response to the HIV epidemic among PWID has been fractured. A crucial lesson is that when evidence-based responses to HIV prevention are undermined or abandoned because of moral objections, untold humanitarian and financial costs on public health will ensue. Restructuring a path forward requires that evidence-based interventions be integrated and brought to scale while simultaneously addressing underlying structural drivers of HIV and related syndemics. Failing to do so will mean that HIV outbreaks among PWID and the communities they live in will continue to occur in a tragic and relentless cycle.
- Published
- 2020
- Full Text
- View/download PDF
23. Do I Have HIV or Not? Lack of RNA Detection and the Case for Sensitive DNA Testing.
- Author
-
Springer SA, Masciotra S, Johnson JA, and Campbell S
- Abstract
We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2020
- Full Text
- View/download PDF
24. Beyond Antibiotics: A Practical Guide for the Infectious Disease Physician to Treat Opioid Use Disorder in the Setting of Associated Infectious Diseases.
- Author
-
Seval N, Eaton E, and Springer SA
- Abstract
Infections are a common cause of hospitalization for patients with opioid use disorder (OUD), and hospital admissions are rising in the context of the worsening US opioid crisis. Infectious disease (ID) physicians are frequently the first point of medical contact for these patients. In this article, we discuss the integration of evidence-based management of OUD and patient-centered care of hospitalized persons with acute injection-related infections. We describe the following components of a comprehensive approach for OUD with inpatient ID consultations: (1) how to screen for OUD; (2) how to initiate the 3 US Food and Drug Administration-approved medications for OUD (buprenorphine, methadone, and extended-release naltrexone); (3) how to manage acute pain and opioid-related conditions; and (4) how to link and integrate ID and OUD treatment after hospital discharge. These strategies reduce unplanned discharges and increase completion of recommended antimicrobial regimens., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2019
- Full Text
- View/download PDF
25. Self-reported antiretroviral therapy adherence and viral load in criminal justice-involved populations.
- Author
-
Cunningham WE, Nance RM, Golin CE, Flynn P, Knight K, Beckwith CG, Kuo I, Spaulding A, Taxman FS, Altice F, Delaney JA, Crane HM, and Springer SA
- Subjects
- Adult, Anti-Retroviral Agents therapeutic use, CD4 Lymphocyte Count, Cohort Studies, Criminal Law, Female, HIV metabolism, HIV Infections drug therapy, Health Status, Humans, Logistic Models, Male, Middle Aged, Young Adult, Antiretroviral Therapy, Highly Active, Criminals, Medication Adherence, Self Report, Viral Load
- Abstract
Background: Self-reported antiretroviral therapy (ART) adherence measures that are associated with plasma viral load (VL) are valuable to clinicians and researchers, but are rarely examined among groups vulnerable to dropping out of care. One-seventh of all those living with HIV pass through incarceration annually and criminal-justice (CJ) involved people living with HIV (PLH) are vulnerable to falling out of care. We examined the association of self-reported ART adherence with VL in a criminal-justice sample compared to a routine-care sample., Methods: Samples: We examined data from a multisite collaboration of studies addressing the continuum of HIV care among CjJ involved persons in the Seek, Test, Treat, and Retain cohort. Data pooled from seven CJ- studies (n = 414) were examined and compared with the routine-care sample from the Centers for AIDS Research Network of Integrated Clinical Systems' seven sites (n = 11,698)., Measures: In both samples, data on self-reported percent ART doses taken were collected via the visual analogue scale adherence measure. Viral load data were obtained by blood-draw., Analysis: We examined the associations of adherence with VL in both cohorts using mixed effects linear regression of log-VL, and mixed effects logistic regression of binary VL (≥ 200 copies/mL) outcomes. Interactions by CD4 count and self-reported health status were also tested., Results: Among the CJ sample, the coefficient for log-VL was - 0.31 (95% CI = - 0.43, - 0.18; P < 0.01) and that in the routine-care sample was - 0.42 (95% CI = - 0.45, - 0.38; P < 0.01). For the logistic regression of binary detectable VL on 10% increments of adherence we found the coefficient was - 0.26 (95% CI = - 0.37, - 0.14; P < 0.01) and in the routine-care sample it was - 0.38 (95% CI = - 0.41, - 0.35; P < 0.01). There was no significant interaction by CD4 count level in the CJ sample, but there was in the routine-care sample. Conversely, there was a significant interaction by self-reported health status level in the criminal-justice sample, but not in the routine-care sample., Conclusions: The visual analogue scale is valid and useful to measure ART adherence, supporting treatment for CJ- involved PLH vulnerable to falling out of care. Research should examine adherence and VL in additional populations.
- Published
- 2019
- Full Text
- View/download PDF
26. Reduced Sexual Risk Behaviors Among Persons With HIV After Release From the Criminal Justice System.
- Author
-
Biondi BE, Frank C, Horn BP, and Springer SA
- Abstract
Background: HIV prevalence is 3 times greater for those in the criminal justice system than the general population, with an assumed increase in sexual risk behaviors (SRBs) postrelease. HIV viral suppression impacts HIV transmission; however, studies of SRBs among persons with HIV leaving the criminal justice system are limited, and no studies have examined viral suppression in relation to SRBs in persons leaving the criminal justice system., Methods: Data were examined from 2 double-blind placebo-controlled trials of extended-release naltrexone among persons with HIV and alcohol use or opioid use disorder. Participants self-reported sexual activity, including number of sexual partners, sex type, and condom use. HIV viral suppression was evaluated prerelease and at 6 months., Results: Thirty days before incarceration, 60% reported having sex compared with 41% and 46%, respectively, at months 1 and 6 postrelease. The number of sex partners and sexual intercourse events decreased from pre-incarceration to months 1 and 6 postrelease. Condom use increased but was not statistically significant. Of the 11 (9.7%) who reported having sex without a condom 1 month postrelease, only 2 did not have viral suppression (VS; HIV VL <200 copies/mL), whereas the 7 (6.5%) who reported SRBs at 6 months all had VS., Conclusions: After release, SRBs decreased, and among those who reported SRBs, most were virally suppressed, and thus risk of transmitting HIV was low., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2019
- Full Text
- View/download PDF
27. Extended-release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living with HIV and Alcohol use Disorders Transitioning to the Community: Results From a Double-Blind, Placebo-Controlled Trial.
- Author
-
Springer SA, Di Paola A, Barbour R, Azar MM, and Altice FL
- Subjects
- Adult, Alcoholism complications, Double-Blind Method, Female, HIV Infections complications, HIV-1 genetics, HIV-1 isolation & purification, Humans, Male, Opioid-Related Disorders complications, Placebos, RNA, Viral blood, Alcohol Deterrents administration & dosage, Alcoholism drug therapy, Delayed-Action Preparations administration & dosage, HIV Infections virology, Naltrexone administration & dosage, Narcotic Antagonists administration & dosage, Opioid-Related Disorders drug therapy, Prisoners, Viral Load
- Abstract
Objective: To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among incarcerated individuals with HIV and alcohol use disorders (AUDs) transitioning to the community., Design: A randomized, double-blind, placebo-controlled trial was conducted among incarcerated individuals with HIV and AUDs transitioning to the community from 2010 through 2016., Methods: Eligible participants (N = 100) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 67) or placebo (n = 33) starting at release and continued for 6 months. The primary and secondary outcomes were the proportion that maintained or improved VS at <200 and <50 copies per milliliter from baseline to 6 months, respectively, using an intention-to-treat analysis., Results: Participants allocated to XR-NTX improved VS from baseline to 6 months for <200 copies per milliliter (48.0%-64.2%, P = 0.024) and for <50 copies per milliliter (31.0%-56.7%, P = 0.001), whereas the placebo group did not (<200 copies/mL: 64%-42.4%, P = 0.070; <50 copies/mL: 42.0%-30.3%, P = 0.292). XR-NTX participants were more likely to achieve VS than the placebo group at 6 months (<200 copies/mL: 64.2% vs. 42.4%; P = 0.041; <50 copies/mL: 56.7% vs. 30.3%; P = 0.015). XR-NTX independently predicted VS [<200 copies/mL: adjusted odds ratio (aOR) = 2.68, 95% confidence interval (CI) = 1.01 to 7.09, P = 0.047; <50 copies/mL: aOR = 4.54; 95% CI = 1.43 to 14.43, P = 0.009] as did receipt of ≥3 injections (<200 copies/mL: aOR = 3.26; 95% CI = 1.26 to 8.47, P = 0.010; <50 copies/mL: aOR = 6.34; 95% CI = 2.08 to 19.29, P = 0.001). Reductions in alcohol consumption (aOR = 1.43, 95% CI = 1.03 to 1.98, P = 0.033) and white race (aOR = 5.37, 95% CI = 1.08 to 27.72, P = 0.040) also predicted VS at <50 copies per milliliter., Conclusions: XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV and AUDs.
- Published
- 2018
- Full Text
- View/download PDF
28. Risk behaviors and HIV care continuum outcomes among criminal justice-involved HIV-infected transgender women and cisgender men: Data from the Seek, Test, Treat, and Retain Harmonization Initiative.
- Author
-
Beckwith CG, Kuo I, Fredericksen RJ, Brinkley-Rubinstein L, Cunningham WE, Springer SA, Loeliger KB, Franks J, Christopoulos K, Lorvick J, Kahana SY, Young R, Seal DW, Zawitz C, Delaney JA, Crane HM, and Biggs ML
- Subjects
- Continuity of Patient Care, Criminal Law, Databases, Factual, Female, Humans, Male, Sexual Partners, United States, HIV Infections drug therapy, Prisoners, Risk-Taking, Transsexualism
- Abstract
Background: Transgender persons are highly victimized, marginalized, disproportionately experience incarceration, and have alarmingly increased rates of HIV infection compared to cis-gender persons. Few studies have examined the HIV care continuum outcomes among transgender women (TW), particularly TW who are involved with the criminal justice (CJ) system., Methods: To improve our understanding of HIV care continuum outcomes and risk behaviors among HIV-infected TW who are involved with the CJ system, we analyzed data from the National Institute on Drug Abuse-supported Seek, Test, Treat, Retain (STTR) Data Harmonization Initiative. Baseline data were pooled and analyzed from three U.S. STTR studies to examine HIV risk and care continuum indicators among CJ-involved HIV-infected TW compared to cisgender men (CM), matched on age (within 5 years) and study at a ratio of 1:5., Results: Eighty-eight TW and 440 CM were included in the study. Among matched participants, TW were more likely to report crack and cocaine use compared to CM (40%,16% respectively, p<0.001); both TW and CM reported high rates of condomless sex (58%, 64%, respectively); TW were more likely than CM to have more than one sexual partner (OR = 2.9, 95% CI: 1.6, 5.2; p<0.001) and have engaged in exchange sex (OR = 3.9, 95% CI: 2.3, 6.6; p<0.001). There were no significant differences between TW and CM in the percentage currently taking ART (52%, 49%, respectively), the mean percent adherence to ART (77% for both groups), and the proportion who achieved viral suppression (61%, 58%, respectively)., Conclusions: HIV-infected CJ-involved TW and CM had similar use of ART and viral suppression but TW were more likely than matched CM to engage in exchange sex, have multiple sexual partners, and use crack/cocaine. TW and CM had similarly high rates of condomless sex and use of other drugs. TW require tailored risk reduction interventions, however both CJ-involved TW and CM require focused attention to reduce HIV risk and improve HIV continuum of care outcomes., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
29. Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial.
- Author
-
Springer SA, Di Paola A, Azar MM, Barbour R, Biondi BE, Desabrais M, Lincoln T, Skiest DJ, and Altice FL
- Subjects
- Adult, Criminal Law, Delayed-Action Preparations, Double-Blind Method, Female, Follow-Up Studies, HIV Infections complications, HIV-1, Humans, Injections, Intramuscular, Male, Middle Aged, Multivariate Analysis, Naltrexone administration & dosage, Naltrexone adverse effects, Narcotic Antagonists administration & dosage, Narcotic Antagonists adverse effects, Opioid-Related Disorders complications, Prospective Studies, RNA, Viral, Research Design, Time Factors, Treatment Outcome, Viral Load, HIV Infections drug therapy, Naltrexone therapeutic use, Narcotic Antagonists therapeutic use, Opioid-Related Disorders drug therapy, Prisoners
- Abstract
Objective: To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among prisoners or jail detainees with HIV and opioid use disorder (OUD) transitioning to the community., Design: A 4-site, prospective randomized double-blind, placebo-controlled trial was conducted among prison and jail inmates with HIV and OUD transitioning to the community from September 2010 through March 2016., Methods: Eligible participants (N = 93) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 66) or placebo (n = 27) starting at release and observed for 6 months. The primary outcome was the proportion that maintained or improved VS (<50 copies/mL) from baseline to 6 months., Results: Participants allocated to XR-NTX significantly improved to VS (<50 copies/mL) from baseline (37.9%) to 6 months (60.6%) (P = 0.002), whereas the placebo group did not (55.6% at baseline to 40.7% at 6 months P = 0.294). There was, however, no statistical significant difference in VS levels at 6 months between XR-NTX (60.6%) vs. placebo (40.7%) (P = 0.087). After controlling for other factors, only allocation to XR-NTX (adjusted odds ratio = 2.90; 95% confidence interval = 1.04 to 8.14, P = 0.043) was associated with the primary outcome. Trajectories in VS from baseline to 6 months differed significantly (P = 0.017) between treatment groups, and the differences in the discordant values were significantly different as well (P = 0.041): the XR-NTX group was more likely than the placebo group to improve VS (30.3% vs. 18.5%), maintain VS (30.3% vs. 27.3), and less likely to lose VS (7.6% vs. 33.3%) by 6 months., Conclusions: XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV with OUD.
- Published
- 2018
- Full Text
- View/download PDF
30. The Alzheimer's disease-protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool.
- Author
-
Siddiqui SS, Springer SA, Verhagen A, Sundaramurthy V, Alisson-Silva F, Jiang W, Ghosh P, and Varki A
- Subjects
- Alleles, Alzheimer Disease immunology, Alzheimer Disease metabolism, Alzheimer Disease pathology, Amino Acid Motifs, Bacterial Proteins metabolism, Bacterial Proteins toxicity, Cell Line, Cell Membrane drug effects, Cell Membrane metabolism, Cell Membrane pathology, Humans, Lipopolysaccharides toxicity, Macrophage Activation drug effects, Macrophages drug effects, Macrophages immunology, Macrophages pathology, Microglia cytology, Microglia immunology, Microglia pathology, N-Formylmethionine Leucyl-Phenylalanine toxicity, Nerve Tissue Proteins chemistry, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neuraminidase metabolism, Neuraminidase toxicity, Neutrophil Activation drug effects, Neutrophils drug effects, Neutrophils immunology, Neutrophils pathology, Peroxisomes drug effects, Peroxisomes metabolism, Peroxisomes pathology, Phylogeny, Protein Interaction Domains and Motifs, Protein Isoforms chemistry, Protein Isoforms genetics, Protein Isoforms metabolism, Protein Sorting Signals, Protein Transport drug effects, Sialic Acid Binding Ig-like Lectin 3 chemistry, Sialic Acid Binding Ig-like Lectin 3 genetics, Alzheimer Disease genetics, Genetic Predisposition to Disease, Macrophages metabolism, Microglia metabolism, Neutrophils metabolism, Polymorphism, Single Nucleotide, Sialic Acid Binding Ig-like Lectin 3 metabolism
- Abstract
The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset Alzheimer's disease (LOAD), an apparently human-specific post-reproductive disease. CD33 generates two splice variants: a full-length CD33M transcript produced primarily by the "LOAD-risk" allele and a shorter CD33m isoform lacking the sialic acid-binding domain produced primarily from the "LOAD-protective" allele. An SNP that modulates CD33 splicing to favor CD33m is associated with enhanced microglial activity. Individuals expressing more protective isoform accumulate less brain β-amyloid and have a lower LOAD risk. How the CD33m isoform increases β-amyloid clearance remains unknown. We report that the protection by the CD33m isoform may not be conferred by what it does but, rather, from what it cannot do. Analysis of blood neutrophils and monocytes and a microglial cell line revealed that unlike CD33M, the CD33m isoform does not localize to cell surfaces; instead, it accumulates in peroxisomes. Cell stimulation and activation did not mobilize CD33m to the surface. Thus, the CD33m isoform may neither interact directly with amyloid plaques nor engage in cell-surface signaling. Rather, production and localization of CD33m in peroxisomes is a way of diminishing the amount of CD33M and enhancing β-amyloid clearance. We confirmed intracellular localization by generating a CD33m-specific monoclonal antibody. Of note, CD33 is the only Siglec with a peroxisome-targeting sequence, and this motif emerged by convergent evolution in toothed whales, the only other mammals with a prolonged post-reproductive lifespan. The CD33 allele that protects post-reproductive individuals from LOAD may have evolved by adaptive loss-of-function, an example of the less-is-more hypothesis., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2017
- Full Text
- View/download PDF
31. Cohort profile: seek, test, treat and retain United States criminal justice cohort.
- Author
-
Chandler R, Gordon MS, Kruszka B, Strand LN, Altice FL, Beckwith CG, Biggs ML, Cunningham W, Chris Delaney JA, Flynn PM, Golin CE, Knight K, Kral AH, Kuo I, Lorvick J, Nance RM, Ouellet LJ, Rich JD, Sacks S, Seal D, Spaulding A, Springer SA, Taxman F, Wohl D, Young JD, Young R, and Crane HM
- Subjects
- Adolescent, Adult, Aged, Cohort Studies, Comorbidity, Female, HIV Infections diagnosis, HIV Infections drug therapy, Health Services Accessibility, Hepatitis C diagnosis, Hepatitis C drug therapy, Humans, Male, Middle Aged, Quality of Life, Risk Factors, Social Class, Social Support, United States epidemiology, Young Adult, Criminal Law, HIV Infections epidemiology, Hepatitis C epidemiology, Mental Disorders epidemiology, Substance-Related Disorders epidemiology
- Abstract
Background: The STTR treatment cascade provides a framework for research aimed at improving the delivery of services, care and outcomes of PLWH. The development of effective approaches to increase HIV diagnoses and engage PLWH in subsequent steps of the treatment cascade could lead to earlier and sustained ART treatment resulting in viral suppression. There is an unmet need for research applying the treatment cascade to improve outcomes for those with criminal justice involvement., Methods: The Seek, Test, Treat, and Retain (STTR) criminal justice (CJ) cohort combines data from 11 studies across the HIV treatment cascade that focused on persons involved in the criminal justice system, often but not exclusively for reasons related to substance use. The studies were conducted in a variety of CJ settings and collected information across 11 pre-selected domains: demographic characteristics, CJ involvement, HIV risk behaviors, HIV and/or Hepatitis C infections, laboratory measures of CD4 T-cell count (CD4) and HIV RNA viral load (VL), mental illness, health related quality of life (QoL), socioeconomic status, health care access, substance use, and social support., Results: The STTR CJ cohort includes data on 11,070 individuals with and without HIV infection who range in age from 18 to 77 years, with a median age at baseline of 37 years. The cohort reflects racial, ethnic and gender distributions in the U.S. CJ system, and 64% of participants are African-American, 12% are Hispanic and 83% are men. Cohort members reported a wide range of HIV risk behaviors including history of injection drug use and, among those who reported on pre-incarceration sexual behaviors, the prevalence of unprotected sexual intercourse ranged across studies from 4% to 79%. Across all studies, 53% percent of the STTR CJ cohort reported recent polysubstance use., Conclusions: The STTR CJ cohort is comprised of participants from a wide range of CJ settings including jail, prison, and community supervision who report considerable diversity in their characteristics and behavioral practices. We have developed harmonized measures, where feasible, to improve the integration of these studies together to answer questions that cannot otherwise be addressed.
- Published
- 2017
- Full Text
- View/download PDF
32. Reply to Liu and Jiang: Maintenance of postreproductive cognitive capacity by inclusive fitness.
- Author
-
Springer SA, Schwarz F, Altheide TK, Varki NM, Varki A, and Gagneux P
- Subjects
- Animals, Humans, Alzheimer Disease genetics, Brain physiopathology, Cognition Disorders genetics, Genetic Fitness, Sialic Acid Binding Ig-like Lectin 3 physiology
- Published
- 2016
- Full Text
- View/download PDF
33. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline.
- Author
-
Schwarz F, Springer SA, Altheide TK, Varki NM, Gagneux P, and Varki A
- Subjects
- Alleles, Alternative Splicing, Animals, Apolipoproteins E genetics, Biological Evolution, Cerebrovascular Disorders genetics, Fertility genetics, Genetic Loci, Humans, Pan troglodytes, Selection, Genetic, Sialic Acid Binding Ig-like Lectin 3 genetics, Alzheimer Disease genetics, Brain physiopathology, Cognition Disorders genetics, Genetic Fitness, Sialic Acid Binding Ig-like Lectin 3 physiology
- Abstract
The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer's dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer's disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin.
- Published
- 2016
- Full Text
- View/download PDF
34. Evolutionary Analysis and Classification of OATs, OCTs, OCTNs, and Other SLC22 Transporters: Structure-Function Implications and Analysis of Sequence Motifs.
- Author
-
Zhu C, Nigam KB, Date RC, Bush KT, Springer SA, Saier MH Jr, Wu W, and Nigam SK
- Subjects
- Amino Acid Transport Systems, Neutral metabolism, Animals, Biological Evolution, Carnitine metabolism, Humans, Mice, Multigene Family, Organic Anion Transporters metabolism, Organic Cation Transport Proteins metabolism, Phylogeny, Polymorphism, Single Nucleotide genetics, Protein Structure, Tertiary, Amino Acid Transport Systems, Neutral genetics, Biological Transport genetics, Organic Anion Transporters genetics, Organic Cation Transport Proteins genetics
- Abstract
The SLC22 family includes organic anion transporters (OATs), organic cation transporters (OCTs) and organic carnitine and zwitterion transporters (OCTNs). These are often referred to as drug transporters even though they interact with many endogenous metabolites and signaling molecules (Nigam, S.K., Nature Reviews Drug Discovery, 14:29-44, 2015). Phylogenetic analysis of SLC22 supports the view that these transporters may have evolved over 450 million years ago. Many OAT members were found to appear after a major expansion of the SLC22 family in mammals, suggesting a physiological and/or toxicological role during the mammalian radiation. Putative SLC22 orthologs exist in worms, sea urchins, flies, and ciona. At least six groups of SLC22 exist. OATs and OCTs form two Major clades of SLC22, within which (apart from Oat and Oct subclades), there are also clear Oat-like, Octn, and Oct-related subclades, as well as a distantly related group we term "Oat-related" (which may have different functions). Based on available data, it is arguable whether SLC22A18, which is related to bacterial drug-proton antiporters, should be assigned to SLC22. Disease-causing mutations, single nucleotide polymorphisms (SNPs) and other functionally analyzed mutations in OAT1, OAT3, URAT1, OCT1, OCT2, OCTN1, and OCTN2 map to the first extracellular domain, the large central intracellular domain, and transmembrane domains 9 and 10. These regions are highly conserved within subclades, but not between subclades, and may be necessary for SLC22 transporter function and functional diversification. Our results not only link function to evolutionarily conserved motifs but indicate the need for a revised sub-classification of SLC22.
- Published
- 2015
- Full Text
- View/download PDF
35. Drug Treatment as HIV Prevention Among Women and Girls Who Inject Drugs From a Global Perspective: Progress, Gaps, and Future Directions.
- Author
-
Springer SA, Larney S, Alam-Mehrjerdi Z, Altice FL, Metzger D, and Shoptaw S
- Subjects
- Female, Global Health, Humans, Ukraine epidemiology, HIV Infections etiology, HIV Infections prevention & control, Substance Abuse, Intravenous complications, Substance Abuse, Intravenous therapy, Women's Health Services organization & administration
- Abstract
Although there have been significant reductions in the number of new HIV infections globally from 2009 to 2013, incidence remains unacceptably high for persons who use drugs. In many settings, women and girls who inject drugs (WWID) with HIV/AIDS experience poor treatment access, including evidence-based practices like antiretroviral therapy and drug treatment. Medication-assisted therapies (MAT) for substance use disorders are especially inaccessible, which in their absence, increases HIV transmission risk. Irrespective of setting or culture, drug treatment using MAT is not only effective but also cost-effective at reducing opioid use and linked injection and sexual risks. Data presented here for WWID address their access to MAT for opioid addiction and to treatments being developed that address the relationship, family, and vocational needs of this group. The most glaring finding is that globally, WWID frequently are excluded in surveys or studies with an impressive lack of disaggregated data by gender when surveying access to MAT—even in wealthy countries. Despite this, there have been some striking improvements in implementing drug treatment as prevention, notably in Iran and China. Still, real barriers remain for women and girls to accessing drug treatment, other harm reduction services, and antiretroviral therapy. Development and/or implementation of interventions that facilitate women and girls engaging in drug treatment that address their roles within society, work, and family/relationships, and outcome evaluation of these interventions are crucial.
- Published
- 2015
- Full Text
- View/download PDF
36. A comparison of psychiatric diagnoses among HIV-infected prisoners receiving combination antiretroviral therapy and transitioning to the community.
- Author
-
Di Paola A, Altice FL, Powell ML, Trestman RL, and Springer SA
- Abstract
Background: The criminal justice system (CJS), specifically prisons and jails, is ideally suited for uniform screening of psychiatric (PD) and substance use disorders (SUDs) among people living with HIV/AIDS (PLWHA), who are concentrated in these settings. By accurately diagnosing PDs and SUDs in these controlled settings, treatment can be initiated and contribute to improved continuity of care upon release. In the context of PLWHA, it may also improve combination antiretroviral treatment (cART) adherence, and reduce HIV transmission risk behaviors., Methods: A retrospective data analysis was conducted by creating a cohort of PLWHA transitioning to the community from prison or jail enrolled who were enrolled in a controlled trial of directly administered antiretroviral (DAART). Participants were systematically assessed for PDs and SUDs using the Mini International Neuropsychiatric Interview (MINI), a standardized psychiatric assessment tool, and compared to diagnoses documented within the correctional medical record., Results: Findings confirm a high prevalence of Axis I PDs (47.4%) and SUDs (67.1%) in PLWHA even after prolonged abstinence from alcohol and drugs. Although prevalence of PDs and SUDs were high in the medical record, there was fair to poor agreement among PDs using the MINI, making evident the potential benefit of more objective and concurrent PD assessments to guide treatment., Conclusions: Additional PD diagnoses may be detected in PLWHA in CJS using supplementary and objective screening tools. By identifying and treating PDs and SUDs in the CJS, care may be improved and may ultimately contribute to healthier outcomes after community release if patients are effectively transitioned.
- Published
- 2014
- Full Text
- View/download PDF
37. Glycan evolution in response to collaboration, conflict, and constraint.
- Author
-
Springer SA and Gagneux P
- Subjects
- Animals, Epistasis, Genetic, Evolution, Molecular, Glycomics methods, Glycomics trends, Glycoproteins genetics, Humans, Mutation, Proteins genetics, Glycoproteins metabolism, Polysaccharides metabolism, Proteins metabolism
- Abstract
Glycans, oligo- and polysaccharides secreted or attached to proteins and lipids, cover the surfaces of all cells and have a regulatory capacity and structural diversity beyond any other class of biological molecule. Glycans may have evolved these properties because they mediate cellular interactions and often face pressure to evolve new functions rapidly. We approach this idea two ways. First, we discuss evolutionary innovation. Glycan synthesis, regulation, and mode of chemical interaction influence the spectrum of new forms presented to evolution. Second, we describe the evolutionary conflicts that arise when alleles and individuals interact. Glycan regulation and diversity are integral to these biological negotiations. Glycans are tasked with such an amazing diversity of functions that no study of cellular interaction can begin without considering them. We propose that glycans predominate the cell surface because their physical and chemical properties allow the rapid innovation required of molecules on the frontlines of evolutionary conflict.
- Published
- 2013
- Full Text
- View/download PDF
38. Duplicate abalone egg coat proteins bind sperm lysin similarly, but evolve oppositely, consistent with molecular mimicry at fertilization.
- Author
-
Aagaard JE, Springer SA, Soelberg SD, and Swanson WJ
- Subjects
- Animals, Female, Gastropoda genetics, Gastropoda metabolism, Male, Molecular Mimicry, Mucoproteins genetics, Mucoproteins metabolism, Phylogeny, Reproductive Isolation, Egg Proteins genetics, Egg Proteins metabolism, Evolution, Molecular, Fertilization genetics, Selection, Genetic, Spermatozoa metabolism
- Abstract
Sperm and egg proteins constitute a remarkable paradigm in evolutionary biology: despite their fundamental role in mediating fertilization (suggesting stasis), some of these molecules are among the most rapidly evolving ones known, and their divergence can lead to reproductive isolation. Because of strong selection to maintain function among interbreeding individuals, interacting fertilization proteins should also exhibit a strong signal of correlated divergence among closely related species. We use evidence of such molecular co-evolution to target biochemical studies of fertilization in North Pacific abalone (Haliotis spp.), a model system of reproductive protein evolution. We test the evolutionary rates (d(N)/d(S)) of abalone sperm lysin and two duplicated egg coat proteins (VERL and VEZP14), and find a signal of co-evolution specific to ZP-N, a putative sperm binding motif previously identified by homology modeling. Positively selected residues in VERL and VEZP14 occur on the same face of the structural model, suggesting a common mode of interaction with sperm lysin. We test this computational prediction biochemically, confirming that the ZP-N motif is sufficient to bind lysin and that the affinities of VERL and VEZP14 are comparable. However, we also find that on phylogenetic lineages where lysin and VERL evolve rapidly, VEZP14 evolves slowly, and vice versa. We describe a model of sexual conflict that can recreate this pattern of anti-correlated evolution by assuming that VEZP14 acts as a VERL mimic, reducing the intensity of sexual conflict and slowing the co-evolution of lysin and VERL., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
- Full Text
- View/download PDF
39. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.
- Author
-
Springer SA, Qiu J, Saber-Tehrani AS, and Altice FL
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Naloxone therapeutic use, Opioid-Related Disorders virology, Prospective Studies, Treatment Outcome, Buprenorphine therapeutic use, HIV Infections drug therapy, Opioid-Related Disorders diet therapy, Prisoners
- Abstract
Introduction: HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX) as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD)., Methods: From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART) for released HIV-infected prisoners; 50 (53%) selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47%) selected no BPN/NLX therapy. Maximum viral suppression (MVS), defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44) groups., Results: The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%), from Hartford (74.4% v 47.7%) and have higher mean global health quality of life indicator scores (54.18 v 51.40). MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1)], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1)] and negatively with being Black [AOR = 0.13 (0.03, 0.68)]. Receiving DAART or methadone did not correlate with MVS., Conclusions: In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.
- Published
- 2012
- Full Text
- View/download PDF
40. Sexual selection by female immunity against paternal antigens can fix loss of function alleles.
- Author
-
Ghaderi D, Springer SA, Ma F, Cohen M, Secrest P, Taylor RE, Varki A, and Gagneux P
- Subjects
- Animals, Antigens immunology, Female, Gene Frequency, Genetics, Population, Humans, Male, Mice, Mice, Knockout, Mixed Function Oxygenases metabolism, Pan troglodytes metabolism, Spermatozoa immunology, Spermatozoa metabolism, Antibodies immunology, Mating Preference, Animal physiology, Mixed Function Oxygenases genetics, Neuraminic Acids immunology, Pan troglodytes immunology, Selection, Genetic, Sialic Acids metabolism
- Abstract
Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(-/-) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-of-function alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-of-function allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines.
- Published
- 2011
- Full Text
- View/download PDF
41. Public health implications for adequate transitional care for HIV-infected prisoners: five essential components.
- Author
-
Springer SA, Spaulding AC, Meyer JP, and Altice FL
- Subjects
- Case Management, HIV Infections epidemiology, Humans, Mental Disorders therapy, Prisons organization & administration, Public Health Administration, Risk Factors, Substance-Related Disorders prevention & control, Substance-Related Disorders therapy, United States epidemiology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections prevention & control, Prisoners
- Abstract
In the United States, 10 million inmates are released every year, and human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) prevalence is several-fold greater in criminal justice populations than in the community. Few effective linkage-to-the-community programs are currently available for prisoners infected with HIV. As a result, combination antiretroviral therapy (cART) is seldom continued after release, and virological and immunological outcomes worsen. Poor HIV treatment outcomes result from a myriad of obstacles that released prisoners face upon reentering the community, including homelessness, lack of medical insurance, relapse to drug and alcohol use, and mental illness. This article will focus on 5 distinct factors that contribute significantly to treatment outcomes for released prisoners infected with HIV and have profound individual and public health implications: (1) adaptation of case management services to facilitate linkage to care; (2) continuity of cART; (3) treatment of substance use disorders; (4) continuity of mental illness treatment; and (5) reducing HIV-associated risk-taking behaviors as part of secondary prevention.
- Published
- 2011
- Full Text
- View/download PDF
42. HIV Treatment in the Criminal Justice System: Critical Knowledge and Intervention Gaps.
- Author
-
Meyer JP, Chen NE, and Springer SA
- Abstract
The criminal justice system bears a disproportionate burden of the HIV epidemic. Continuity of care is critical for HAART-based prevention of HIV-related morbidity and mortality. This paper describes four major challenges to successful management of HIV in the criminal justice system: relapse to substance use, homelessness, mental illness, and loss of medical and social benefits. Each of these areas constitutes a competing priority upon release that demands immediate attention and diverts time, energy, and valuable resources away from engagement in care and adherence to HAART. Numerous gaps exist in scientific knowledge about these issues and potential solutions. In illuminating these knowledge deficits, we present a contemporary research agenda for the management of HIV in correctional systems. Future empirical research should focus on these critical issues in HIV-infected prisoners and releasees while interventional research should incorporate evidence-based solutions into the criminal justice setting.
- Published
- 2011
- Full Text
- View/download PDF
43. Advances in the prevention of heterosexual transmission of HIV/AIDS among women in the United States.
- Author
-
Chen NE, Meyer JP, and Springer SA
- Abstract
Despite recent advances in testing and treatment, the incidence of HIV/AIDS in the United States has remained stagnant with an estimated 56,300 new infections every year. Women account for an increasing proportion of the epidemic. The vulnerability of women to HIV stems from both increased biologic susceptibility to heterosexual transmission and also the social, economic, and structural disadvantages they often confront. This review describes the main reasons for the increased vulnerability of U.S. women to HIV transmission with particular emphasis on specific high-risk groups including: non-Hispanic blacks, women who use drugs, women with a history of incarceration, and victims of intimate partner violence. Although behavioral approaches to HIV prevention may be effective, pragmatic implementation is often difficult, especially for women who lack sociocultural capital to negotiate condoms with their male partners. Recent advances in HIV prevention show promise in terms of female-initiated interventions. These notably include female condoms, non-specific vaginal microbicides, and antiretroviral oral and vaginal pre-exposure prophylaxis. In this review, we will present evidence in support of these new female-initiated interventions while also emphasizing the importance of advocacy and the political support for these scientific advances to be successful.
- Published
- 2011
- Full Text
- View/download PDF
44. Improved HIV and substance abuse treatment outcomes for released HIV-infected prisoners: the impact of buprenorphine treatment.
- Author
-
Springer SA, Chen S, and Altice FL
- Subjects
- Buprenorphine, Naloxone Drug Combination, CD4 Lymphocyte Count, Female, Humans, Male, Mental Disorders complications, Methadone therapeutic use, Middle Aged, Narcotics therapeutic use, Substance-Related Disorders complications, Anti-Retroviral Agents therapeutic use, Buprenorphine therapeutic use, HIV Infections drug therapy, Naloxone therapeutic use, Narcotic Antagonists therapeutic use, Prisoners, Substance-Related Disorders drug therapy
- Abstract
HIV-infected prisoners fare poorly after release. Though rarely available, opioid agonist therapy (OAT) may be one way to improve HIV and substance abuse treatment outcomes after release. Of the 69 HIV-infected prisoners enrolled in a randomized controlled trial of directly administered antiretroviral therapy, 48 (70%) met DSM-IV criteria for opioid dependence. Of these, 30 (62.5%) selected OAT, either as methadone (N = 7, 14.5%) or buprenorphine/naloxone (BPN/NLX; N = 23, 48.0%). Twelve-week HIV and substance abuse treatment outcomes are reported as a sub-study for those selecting BPN/NLX. Retention was high: 21 (91%) completed BPN/NLX induction and 17 (74%) remained on BPN/NLX after 12 weeks. Compared with baseline, the proportion with a non-detectable viral load (61% vs 63% log(10) copies/mL) and mean CD4 count (367 vs 344 cells/mL) was unchanged at 12 weeks. Opiate-negative urine testing remained 83% for the 21 who completed induction. Using means from 10-point Likert scales, opioid craving was reduced from 6.0 to 1.8 within 3 days of BPN/NLX induction and satisfaction remained high at 9.5 throughout the 12 weeks. Adverse events were few and mild. BPN/NLX therapy was acceptable, safe and effective for both HIV and opioid treatment outcomes among released HIV-infected prisoners. Future randomized controlled trials are needed to affirm its benefit in this highly vulnerable population.
- Published
- 2010
- Full Text
- View/download PDF
45. Coevolution of interacting fertilization proteins.
- Author
-
Clark NL, Gasper J, Sekino M, Springer SA, Aquadro CF, and Swanson WJ
- Subjects
- Animals, Egg Proteins metabolism, Female, Fertilization, Gastropoda metabolism, Genetic Speciation, Male, Mucoproteins metabolism, Polymorphism, Genetic, Receptors, Cell Surface metabolism, Egg Proteins genetics, Evolution, Molecular, Gastropoda genetics, Mucoproteins genetics, Receptors, Cell Surface genetics
- Abstract
Reproductive proteins are among the fastest evolving in the proteome, often due to the consequences of positive selection, and their rapid evolution is frequently attributed to a coevolutionary process between interacting female and male proteins. Such a process could leave characteristic signatures at coevolving genes. One signature of coevolution, predicted by sexual selection theory, is an association of alleles between the two genes. Another predicted signature is a correlation of evolutionary rates during divergence due to compensatory evolution. We studied female-male coevolution in the abalone by resequencing sperm lysin and its interacting egg coat protein, VERL, in populations of two species. As predicted, we found intergenic linkage disequilibrium between lysin and VERL, despite our demonstration that they are not physically linked. This finding supports a central prediction of sexual selection using actual genotypes, that of an association between a male trait and its female preference locus. We also created a novel likelihood method to show that lysin and VERL have experienced correlated rates of evolution. These two signatures of coevolution can provide statistical rigor to hypotheses of coevolution and could be exploited for identifying coevolving proteins a priori. We also present polymorphism-based evidence for positive selection and implicate recent selective events at the specific structural regions of lysin and VERL responsible for their species-specific interaction. Finally, we observed deep subdivision between VERL alleles in one species, which matches a theoretical prediction of sexual conflict. Thus, abalone fertilization proteins illustrate how coevolution can lead to reproductive barriers and potentially drive speciation., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2009
- Full Text
- View/download PDF
46. Persistence of virological benefits following directly administered antiretroviral therapy among drug users: results from a randomized controlled trial.
- Author
-
Maru DS, Bruce RD, Walton M, Springer SA, and Altice FL
- Subjects
- Adult, CD4 Lymphocyte Count, Female, HIV Infections complications, HIV Infections virology, HIV-1 genetics, HIV-1 physiology, Humans, Male, Middle Aged, Patient Compliance, RNA, Viral blood, Self Administration, Social Support, Treatment Outcome, Anti-HIV Agents administration & dosage, Anti-HIV Agents therapeutic use, Directly Observed Therapy, HIV Infections drug therapy, HIV-1 drug effects, Substance-Related Disorders complications
- Abstract
Background: Although directly administered antiretroviral therapy (DAART) has demonstrated impressive biological benefits compared with self-administered therapy (SAT) among drug users, the persistence of DAART after transition to SAT has not been examined., Methods: We conducted a community-based, prospective, randomized controlled trial of 6 months of DAART compared with SAT. The primary outcome was the proportion of subjects who achieved virological success at 6 months postintervention, defined as either a 1.0 log10 reduction from baseline or HIV-1 RNA <400 copies per milliliter. Secondary outcomes included the change from baseline in HIV-1 RNA and CD4 lymphocyte count., Results: Of the 53 subjects in the SAT arm and 88 subjects in the DAART arm, 52 and 82, respectively, provided blood samples at 6 months postintervention. The DAART (n = 88) and SAT (n = 53) arms did not differ on virological success (DAART 58.0% vs. SAT 56.6%, P = 0.64), mean reduction in log10 HIV-1 RNA (-0.79 vs. -0.31 log10 copies/mL, P = 0.53), or mean change in CD4 lymphocyte count (+60.2 vs. -15.4 cells/mL, P = 0.12). In the multivariate analysis, only high levels of social support significantly predicted virological success., Conclusions: This analysis, from the first randomized controlled trial of DAART among active drug users, failed to show the persistence of the DAART intervention at improving virological outcomes. Additional strategies are needed to ensure the on-treatment benefits persist following the cessation of DAART.
- Published
- 2009
- Full Text
- View/download PDF
47. Extraordinary intraspecific diversity in oyster sperm bindin.
- Author
-
Moy GW, Springer SA, Adams SL, Swanson WJ, and Vacquier VD
- Subjects
- Alternative Splicing, Amino Acid Sequence, Animals, Blotting, Western, Electrophoresis, Polyacrylamide Gel, Male, Models, Molecular, Molecular Sequence Data, Ostreidae, Polymorphism, Genetic, Proteins chemistry, Proteins genetics, Recombination, Genetic, Sequence Homology, Amino Acid, Species Specificity, Sperm-Ovum Interactions, Proteins metabolism, Spermatozoa metabolism
- Abstract
In free-spawning invertebrates sperm-egg incompatibility is a barrier to mating between species, and divergence of gamete recognition proteins (GRPs) can result in reproductive isolation. Of interest are processes that create reproductive protein diversity within species, because intraspecific variants are potentially involved in mate choice and early speciation. Sperm acrosomes of the Pacific oyster Crassostrea gigas contain the protein bindin that bonds sperm to egg during fertilization. Oyster bindin is a single-copy gene encoding a diversity of protein variants. Oyster bindins have a conserved N-terminal region followed by one to five tandem fucose-binding lectin (F-lectin) domains. These repeats have diversified by positive selection at eight sites clustered on the F-lectin's fucose binding face. Additional bindin variants result from recombination in an intron in each F-lectin repeat. Males also express alternatively spliced bindin cDNAs with one to five repeats, but typically translate only one or two isoforms into protein. Thus, positive selection, alternative splicing, and recombination can create thousands of bindin variants within C. gigas. Models of sexual conflict predict high male diversity when females are diverse and sexual conflict is strong. The amount of intraspecific polymorphism in male GRPs may be a consequence of the relative efficiency of local (molecular recognition) and global (electrical, cortical, and physical) polyspermy blocks that operate during fertilization.
- Published
- 2008
- Full Text
- View/download PDF
48. Directly administered antiretroviral therapy for HIV-infected drug users does not have an impact on antiretroviral resistance: results from a randomized controlled trial.
- Author
-
Maru DS, Kozal MJ, Bruce RD, Springer SA, and Altice FL
- Subjects
- Adult, Drug Resistance, Viral genetics, Female, HIV Infections virology, HIV-1 genetics, HIV-1 isolation & purification, Humans, Male, Middle Aged, Prospective Studies, Self Administration, Treatment Outcome, Anti-Retroviral Agents administration & dosage, Anti-Retroviral Agents therapeutic use, Drug Therapy methods, HIV Infections complications, HIV Infections drug therapy, Substance-Related Disorders complications
- Abstract
Background: Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown., Methods: We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations., Results: The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ., Conclusion: In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.
- Published
- 2007
- Full Text
- View/download PDF
49. Superiority of directly administered antiretroviral therapy over self-administered therapy among HIV-infected drug users: a prospective, randomized, controlled trial.
- Author
-
Altice FL, Maru DS, Bruce RD, Springer SA, and Friedland GH
- Subjects
- Adult, Directly Observed Therapy methods, Female, HIV Infections complications, HIV-1 drug effects, HIV-1 genetics, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Patient Compliance statistics & numerical data, Prospective Studies, RNA, Viral genetics, RNA, Viral metabolism, Self Administration methods, Treatment Outcome, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, Substance-Related Disorders complications
- Abstract
Background: Directly administered antiretroviral therapy (DAART) is one approach to improve treatment adherence among human immunodeficiency virus (HIV)-infected drug users., Methods: In this randomized, controlled trial (ClinicalTrials.gov identifier, NCT00367172), the biological outcomes of a 6-month community intervention of DAART were compared with those of self-administered therapy among HIV-infected drug users. Patients randomized to receive DAART received supervised therapy 5 days per week from workers in a mobile health care van. The primary outcome, using an intention-to-treat approach, was the proportion of patients achieving either a reduction in HIV-1 RNA level of > or = 1.0 log10 copies/mL or an HIV-1 RNA level < or = 400 copies/mL at 6 months. Secondary outcomes included the mean change from baseline in HIV-1 RNA level and CD4+ T lymphocyte count., Results: Of the 141 patients who met the entry criteria, 88 were randomized to receive DAART, and 53 were randomized to receive self-administered therapy; 74 (84%) of 88 of the patients randomized to receive DAART accepted the intervention. Of the 74 patients who initiated DAART, 51 (69%) completed the full 6-month intervention. At the end of 6 months, a significantly greater proportion of the DAART group achieved the primary outcome (70.5% vs. 54.7; P=.02). Additionally, compared with patients receiving self-administered therapy, patients receiving DAART demonstrated a significantly greater mean reduction in HIV-1 RNA level (-1.16 log10 copies/mL vs. -0.29 log10 copies/mL; P=.03) and mean increase in CD4+ T lymphocyte count (+58.8 cells/microL vs. -24.0 cells/microL; P=.002)., Conclusions: This randomized, controlled trial was, to our knowledge, the first to demonstrate the effectiveness of DAART at improving 6-month virologic outcomes among drug users. These results suggest that DAART should be more widely available in HIV treatment programs that target drug users who have poor adherence to treatment.
- Published
- 2007
- Full Text
- View/download PDF
50. Adaptive gamete-recognition divergence in a hybridizing Mytilus population.
- Author
-
Springer SA and Crespi BJ
- Subjects
- Acrosome metabolism, Amino Acid Sequence, Animals, Base Sequence, DNA Primers, Demography, Likelihood Functions, Male, Models, Genetic, Molecular Sequence Data, Sequence Analysis, DNA, Adaptation, Biological genetics, Alleles, Evolution, Molecular, Hybridization, Genetic genetics, Mucoproteins genetics, Mytilus genetics, Phylogeny, Selection, Genetic
- Abstract
Gamete-recognition proteins often evolve rapidly, but it is not known if their divergence occurs within species and corresponds with the evolution of reproductive isolation, or if divergence typically accumulates between already isolated lineages. We examined the evolution of a candidate gamete-recognition protein in several sympatric and allopatric populations of Mytilus blue mussels, species that hybridize in nature. Within a single species, Mytilus galloprovincialis, we found adaptive divergence of Lysin-M7, a sperm acrosomal protein that dissolves the egg vitelline envelope during fertilization. Mytilus galloprovincialis Lysin-M7 alleles group into two distinct clades (termed G and G(D)), and individual alleles in these clades are separated from each other by at least three and up to eleven amino-acid substitutions. Maximum-likelihood estimates of selective pressure (dN/dS =omega) implicate selection in the divergence between M. galloprovincialis Lysin-M7 clades, and within the G(D) clade. Exact tests of population differentiation indicate that the relative frequency of G and G(D) Lysin-M7 alleles differs significantly among M. galloprovincialis populations. Compared with allopatric Mediterranean samples, Lysin-M7 alleles in the G(D) clade are found at elevated frequency in samples from the East Atlantic and California, areas of secondary contact and hybridization between Mytilus species, and Australia, an area of unknown species composition. Adaptive divergence between the alleles most common in allopatry and those found at elevated frequency in samples from sympatry suggests that selection pressures acting in hybridizing populations, likely following Pleistocene secondary contact with M. edulis in the East Atlantic, drove the divergence of Lysin-M7 in M. galloprovincialis.
- Published
- 2007
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.