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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Contemp Clin Trials. Author manuscript; available in PMC Mar 1, 2013.
Published in final edited form as:
PMCID: PMC3268833
NIHMSID: NIHMS342203
Rationale, Study Design and Sample Characteristics of a Randomized Controlled Trial of Directly Administered Antiretroviral Therapy for HIV-infected Prisoners Transitioning to the Community - A Potential Conduit to Improved HIV Treatment Outcomes
Ali S. Saber Tehrani, M.D., Sandra A. Springer, M.D., Jingjun Qiu, BMed, M.S., Maua Herme, M.P.H., Jeffrey Wickersham, Ph.D., and Frederick L. Altice, M.D., M.A.
Yale University School of Medicine, Department of Medicine, Section of Infectious Diseases, AIDS Program
Contact: Frederick L. Altice, M.D., Address: 135 College Street, Suite 323, New Haven, CT 06510, Phone: 203.737.2883, Facsimile: 203.737.4051, Frederick.altice/at/yale.edu
Background
HIV-infected prisoners experience poor HIV treatment outcomes post-release. Directly administered antiretroviral therapy (DAART) is a CDC-designated, evidence-based adherence intervention for drug users, yet untested among released prisoners.
Methods
Sentenced HIV-infected prisoners on antiretroviral therapy (ART) and returning to New Haven or Hartford, Connecticut were recruited and randomized 2:1 to a controlled trial (RCT) of 6 months of DAART versus self-administered therapy (SAT); all subjects received case management services. Subjects meeting DSM-IV criteria for opioid dependence were offered immediate medication-assisted treatment. Trained outreach workers provided DAART once-daily, seven days per week, including behavioral skills training during the last intervention month. Both study groups were assessed for 6 months after the intervention period. Assessments occurred within 90 days pre-release (baseline), day of release, and then monthly for 12 months. Viral load (VL) and CD4 testing was conducted baseline and quarterly; genotypic resistance testing was conducted at baseline, 6 and 12 months. The primary outcome was pre-defined as viral suppression (VL<400 copies/mL) at 6 months.
Results
Between 2004 and 2009, 279 participants were screened, of which 202 met eligibility criteria and 154 were ultimately enrolled in the study; 103 subjects were randomized to DAART and 51 to SAT. Subjects were mostly male (81.2%), people of color (87.0%), had an alcohol use disorder (39.7%), had underlying depression (54.2%), were virally suppressed (78.8%) and mean CD4=390.7 cells/mL.
Conclusions
Outcomes from this RCT will contribute greatly to HIV treatment outcomes after release from prison, a period associated with adverse HIV and other medical consequences.
Keywords: Adherence, Directly administered antiretroviral therapy, Directly observed therapy, HIV, AIDS, Substance abuse, prisoners, incarceration, DAART, antiretroviral therapy
In 2009, 7.2 million people were involved in the criminal justice system (CJS) in the United States [1] with one sixth of all people living with HIV/AIDS (PLWHA) passing through the CJS annually [2]. As a result of the overwhelming majority of correctional inmates having substance use disorders [3, 4], including injection drug use (IDU) [5], HIV prevalence among incarcerated persons is over three times greater than among the general population.
Though not examined recently, all published studies suggest that the majority of correctional inmates learn about their HIV diagnosis [6, 7] and first initiate antiretroviral therapy (ART) while incarcerated [8], making correctional settings ideal for HIV prevention and treatment initiatives [9]. Treatment for HIV using ART results in optimal outcomes [10, 11], resulting in the reduced mortality among prisoners such that they had reached parity with non-correctional populations by 2008 [12]. Despite these successes within prison, HIV treatment outcomes deteriorate soon after release [10, 13]. Arguably, many attribute the impressive benefits of ART among prisoners to the structure of the prison environment, stabilized housing, near universal access to ART, the relative lack of drug use, the treatment of mental illness and the supervised provision of directly administered antiretroviral therapy (DAART). One of the most pressing issues facing the correctional system today is therefore sustaining the benefit of ART while HIV-infected prisoners transition to community settings [10]. After release, HIV-infected prisoners face seemingly insurmountable social and medical destabilization [13, 14]. The extent to which these factors contribute to poor HIV treatment outcomes after release are complex, yet it is imperative to both the individual and collectively to society to develop effective prison-release interventions that address the unique needs of this population that is at risk for numerous negative health consequences, including overdose and death [15]. Documented problems accessing ART [16] and relapse to drug use [17] contribute to poor post-release HIV treatment outcomes, yet post-release case management services do not ameliorate these negative health outcomes any better than pre-release planning [18].
To overcome poor post-release HIV treatment outcomes, we postulated that providing continued structure, particularly with regard to support ART adherence even in the setting of relapse to drug and alcohol use, was a necessary and important contributor to HIV treatment outcomes under circumstances that were socially and medically destabilizing. Directly administered antiretroviral therapy (DAART) has been thoroughly developed [19] and documented in randomized controlled trials (RCTs) in community settings [20, 21] and now to be designed by the Centers for Disease Control and Prevention as an evidence-based behavioral adherence intervention for drug users [22]. Among active drug users, it has been associated with improved virological and immunological outcomes that are optimized when linked to healthcare and case management [23], has high acceptability, improves adherence and retention [24] and does not promote the development of genotypic resistance mutations [25]. To determine if DAART was effective at stabilizing the treatment outcomes among HIV-infected prisoners transitioning to the community, we therefore conducted a RCT comparing DAART to self-administered therapy on virological, immunological and a number of other treatment outcomes.
Study Design
The CONNECT trial was a two-site, RCT of HIV-infected individuals on stabilized ART who were transitioning from prison to the cities of New Haven or Hartford, Connecticut. The participants were randomized 2:1 to either: (1) directly administered antiretroviral therapy (DAART); or (2) self-administered therapy (SAT) as a control. Both groups received medication adherence counseling at baseline and at six months, and monthly interviews for 12 months. The primary outcome was achieving viral suppression at 6 months, measured at HIV-1 RNA levels < 400 copies/mL. Other outcomes of interest included: 1) changes in HIV-1 RNA levels from baseline; 2) maximum virological suppression defined as HIV-1 RNA < 50 copies/mL at 6 months; 3) change in CD4 from baseline to 6 months; 4) adherence to ART and 5) retention in care. To examine the durability of the intervention, all measures were assessed at 12 months and compared to the end of the intervention period (6 month assessment).
Study Setting
Project CONNECT enrolled subjects from 2004 to 2009 in two research sites in New Haven and Hartford, Connecticut. Unlike our previous studies of DAART,[19] ART was supervised once-daily, seven days per week in community settings by a trained outreach worker. Our previous studies confirmed that non-observed dosing days resulted in significantly lower adherence on those days [19]. All DAART participants were provided a mobile telephone during the 6-month intervention period to enhance daily communication between subjects and DAART outreach workers. For individuals meeting DSM-IV criteria for opioid dependence, they had the option of selecting to also receive buprenorphine as previously described [17]. Subjects prescribed buprenorphine, irrespective of randomization group, had weekly scheduled substance abuse counseling sessions for 12 weeks; the frequency of counseling sessions varied for subjects beyond the first 12 weeks, based on previously described buprenorphine counseling content[26]. For DAART subjects receiving buprenorphine, their buprenorphine was observed daily. Substance abuse counselors provided vouchers for buprenorphine prescription renewals at scheduled counseling sessions.
Study Inclusion and Exclusion Criteria
Participants were primarily recruited from the Connecticut Department of Correction (CTDOC) within 90 days prior to release. Inclusion criteria included: (1) Documentation of HIV-infection; (2) already receiving ART or eligible for it upon release; (3) ART prescribed once or twice daily; (4) incarcerated for a minimum of 90 days; (5) able to communicate in either English or Spanish; (6) returning to the cities of New Haven or Hartford; (7) at least 18 years of age; (8) capable of providing informed consent; and (9) not enrolled in any other adherence research intervention. Individuals who met eligibility requirements who were unexpectedly released from prison, but within 30 days of release, were also eligible for enrollment. Subjects who had pending charges unrelated to their current sentence or whose sentence was extended beyond the funding period were ineligible.
Protection of Human Subjects
Approvals, Confidentiality, and Data Safety and Monitoring
The Yale University Human Investigation Committee and Connecticut Department of Correction Research Advisory Committee approved the trial and it was registered at www.clinicaltrials.gov (NCT00786396). Because the trial involved released prisoners and individuals with substance use disorders with extensive criminal justice experiences, additional assurances were provided by the Office of Human Research Protection (OHRP) at the Department of Health and Human Services and a Certificate of Confidentiality from National Institutes of Health, respectively.
Specific Safety Protocols
All medications, whether dispensed as DAART or SAT, were prepared, packaged and dispensed by a licensed pharmacist. No experimental medications were used. Packaged daily pill and medication boxes were reviewed by clinical staff after preparation by the pharmacist in order to ensure that all medications were accurate to the regimen prescribed for the participant by their medical providers. Regimens were reviewed monthly with the participant and with their provider to ensure accuracy of the prescriptions. Prior to observing a participant taking their daily dose of medication, a review of the names and identification of the medication was done by the participant and research staff. This review was compared to the prescription labels on each medication box and along with a daily regimen tracking form. The tracking form also provided an opportunity to monitor the participant’s side effects, medical needs, participant’s record of non-observed medications and all attempts to be made to ensure the client received their medications for the day. Storage of all medications was kept in a locked cabinets used solely for the storage of medications.
Patient Recruitment, Enrollment, and Reimbursement
The Infectious Disease Contact Nurses (IDCN) within the Connecticut Department of Correction initiates the discharge planning process for all HIV-infected inmates beginning 90 days before expected release. This is accomplished by referring the inmates to Project TLC (Transitional Linkage to the Community) [27], a standard-of-care transitional case management program that develops a discharge plan and assists released individuals for a minimum of 30 days post-release. Project TLC assists with arranging medical appointments, ensuring that each person can continue their antiretroviral medications by completing the AIDS Drug Assistance Program application and making referral to other identified services that are needed. For the purposes of this study, a referral to Project TLC would also result in a simultaneous referral to Project CONNECT for inmates returning to New Haven and Hartford. There were two phases of recruitment. The first phase was eligibility screening and baseline data collection necessary for randomization. After the inmate signed the necessary release of information forms allowing communication between the inmate and research staff, a Project CONNECT staff member traveled to the prison as part of the pre-enrollment process, conducted the baseline assessment and described the details of the study and determined eligibility. The second phase was the formal enrollment into the randomized controlled trial, which only took place after the subject was released from the prison environment, to ensure that final enrolment was not coercive. Ideally, this occurred on the day the subject was released or as soon as possible thereafter, but within 30 days of release. If the subject remained interested in the project, he/she would sign a second consent form and a release of information form to allow further access to medical and drug treatment information for the subsequent 12 months.
Study participants received payments ranging from $10-$50 upon completing follow-up interviews; the amount varied based on the length of the survey and whether the subject had to travel for phlebotomy. No subject received payment for pre-enrollment activities or during any time of their incarceration or for participating in the DAART arm alone.
Randomization
Randomization was based upon data acquired while the subject was in prison (interview and chart review data), allowing for randomization to occur on the day of discharge from prison. Randomization was performed according to a balanced (self-adjusting) randomization scheme incorporating stratified cluster criteria [28, 29]. Randomization included the following factors: 1) returning to New Haven versus Hartford; and 2) presence or absence of an alcohol use disorder based on AUDIT criteria (>8 for men and >6 for women). Randomization was 2:1 for DAART: SAT, with oversampling the DAART group in order to allow for the potential refusal to participate in DAART should the subject not prefer it based on learning of their randomization status. Acceptability of DAART was measured as their willingness to participate in DAART after learning of their randomization status. Any subject meeting DSM-IV criteria for opioid dependence [30] for the 12-month period before incarceration was offered enrolment in buprenorphine or methadone maintenance treatment on the day of release.
Buprenorphine/naloxone was provided free of charge for all interested subjects by Reckitt Benckiser Pharmaceuticals as part of supplemental funding (R21 DA019843; Altice, PI).
Baseline Assessment and Follow-Up Interviews
Baseline information included: 1) demographic characteristics; 2) social circumstances prior to incarceration; 3) presence and severity of co-morbid medical and psychiatric conditions; 4) prior medical history and 5) HIV risk behavior in the 30 days prior to incarceration. Psychiatric and substance use disorders were assessed using the Mini International Neuropsychiatric Interview (MINI) [30] and alcohol use disorders were further measured using the Alcohol Use Disorders Inventory Test (AUDIT) [31]. Additional standardized measures at baseline and follow-up included the HIV symptom index [32], quality of life using the 36-item short-form from the Medical Outcomes Survey (SF-36) [33], the magnitude of depressive symptoms using the Self-Report Quick Inventory of Depressive Symptomatology (QIDS-SR) [34] and the Clinical Epidemiological Survey of Depression (CES-D) [35], social support scale [36], trust in physician scale [37], HIV-related stigma scale [38], neurocognitive impairment using the neuropsychological symptom inventory (NIS) [39] and the Addiction Severity Index [40] and event-level pre-incarceration HIV risk behaviors that were adapted from previous studies [41].
All subjects, after signing the final consent forms to participate, were scheduled for an interview on the day of prison-release where they were introduced to the community research team, further explained study procedures and underwent an additional survey that assessed their experiences in prison, including adherence to antiretroviral therapy using the visual analogue scale (VAS) [42], HIV risk behaviors, drug use and care-related activities. Subjects remained eligible for participation as long as this interview was conducted within 30 days post-release. All interviews were conducted using Audio Computer-Assisted Structured Interview (ACASI) methodology. On the day of release (or within 30 days), each subject underwent urine screening for opioids, cocaine, marijuana, amphetamines and methamphetamines using Reditest (Redwood, Santa Rosa, CA), phlebotomy for CD4 and HIV-1 RNA levels, and assignment to a study group.
Description of the Intervention and Control Conditions
All subjects were assigned to either DAART or SAT for a period of six months. At the end of six months, all subjects were converted to SAT and observed for an additional six months. The details of activities for the first six months for each group are described below. The protocol for both groups for the post-intervention periods (months 7-12) was identical and described subsequently.
Intervention Arm: (Directly Administered Antiretroviral Therapy, DAART)
Many of the DAART procedures have been previously described.[19] All chronically prescribed medications prescribed no more than twice-daily, including antiretroviral medications, were packaged and labeled by a pharmacist in dose packs and placed in a pillbox. For subjects selecting buprenorphine treatment, this medication was also observed as previously reported.[17] DAART subjects were observed to remove one dose per day from their weekly pre-packaged pillboxes and place their second dose (if one was prescribed) in a bottle with a Medication Event Monitoring System (MEMS, Aardex Group) recorder; in this way, the MEMS cap recorded both the morning dose by “placing” the second dose in the container and the evening dose when the subject took it later that day. Unlike our previous intervention where DAART was performed only on weekdays, DAART subjects were observed taking one dose daily seven days per week for the 6-month intervention period. DAART was conducted at selected locations throughout the cities of New Haven and Hartford. Subjects were allowed to select a location in accordance with their preferences (e.g., near their home, a drug treatment program, remote from their family, our research storefront, etc). In general, clients did not travel more than 4 blocks based on findings from our previous DAART studies.[24] DAART subjects were provided mobile telephones with voice and texting capabilities and met the outreach worker every morning between 8am and 11am. Outreach workers would observe and record all medications taken and if a client failed to show, the staff member would make multiple attempts to contact the client to guarantee that medications were delivered to them or that the client took a spare pack that was maintained in the bottle with a MEMS cap that was used to monitor medication adherence beyond observed doses, including multiple dose-per-day regimens. Up to three doses of medications, provided as “spare packs” were provided to all participants in recognition of inclement weather or unanticipated emergencies. Receipt of any more than three spare packs required meeting with the DAART outreach worker. All prescriptions were filled by a collaborating pharmacy that adhered to DAART procedures.
Previous DAART studies failed to confirm that the benefits from DAART persisted beyond the DAART intervention.[43, 44] Therefore, the outreach workers provided standardized supplemental training program that included daily recognition and naming of medications and discussion of missed doses using the Information, Motivation and Behavioral Skills model of adherence.[45] Additionally, beginning in the last month of the intervention, the outreach workers trained subjects to fill their own pillboxes, practice the names of medications, discussed methods of remembering to order refills in a timely manner and how to deal with any missed doses.
Control Arm: (Self-Administered Therapy, SAT)
SAT subjects received their monthly refills from the research pharmacy, which were then checked by the research staff and a MEMS cap was placed on the anchoring antiretroviral medication component. Anchoring medications included either the non-nucleoside reverse transcriptase inhibitor or protease inhibitor medication included in all regimens. Medication refills were scheduled and provided during the monthly structured interview when MEMS cap recordings could be downloaded. Subjects selecting to receive buprenorphine received their medications as SAT weekly for the first 12 weeks and then monthly thereafter. No cell phones were provided to SAT subjects.
Post Intervention Period
After the 6-month intervention period, all subjects were followed for an additional six months to determine the durability of the DAART intervention (post-intervention effect). During this time, refills for both study groups were provided by the research pharmacy and monitored using MEMS; these were the same procedures used for the SAT group during the intervention period. Table 1 summarizes the schedule and contents of the study visits.
Table 1
Table 1
Schedule and contents of study visits
Adherence Counseling
Baseline adherence counseling was provided for all participants regardless of study arm assignment. Counseling consisted of a standardized, 15-minute video that addressed the importance of medication adherence [46], including the association of adherence on viral load, CD4 counts, development of genotypic resistance mutations and dealing with missed doses. At six months, all subjects reviewed the video again and were provided with a comic-style pamphlet produced by Visionary Health Concepts, titled “Blocking the Mutant Invasion” [47].
Laboratory Monitoring
Blood samples
Phlebotomy was performed at pre-scheduled intervals to assess HIV-1 RNA levels (Amplicor 1.5; Roche), CD4 (FACS; Quest) lymphocyte count, and HIV-1 genotypic resistance mutations. All subjects underwent baseline phlebotomy. HIV-1 RNA and CD4 were assessed quarterly and genotypic resistance testing was monitored at 6- and 12-month interview. Quarterly, a standard chemical (including electrolytes, renal function, lipid profile and liver enzymes) and hematological (complete blood count) was also performed as part of routine clinical practice. In cases where the subject’s HIV provider performed phlebotomy, we used laboratory data that were provided by the clinic. Laboratory values were assigned to a designated time point (e.g. 6 months) if they were drawn within 6 weeks of the designated time period. A maximum of 50 mL was drawn at any visit; discard samples were stored and frozen at −80° C. All results were first reviewed by the medical director (SAS) and faxed to the primary HIV care provider. Any laboratory values that involved a Grade III or IV toxicity were discussed by phone with the primary HIV provider to come up with a treatment plan.
Urine drug testing
Urine toxicology screens were conducted monthly for monitoring relapse to drug use using the 6-panel Reditest (Redwood, Santa Rosa, CA); testing for buprenorphine was conducting using the Buprenorphine Reditest (Redwood, Santa Rosa, CA). Positive urine tests are indicative of active drug use of opioids, cocaine, amphetamine, buprenorphine and benzodiazepines in the previous 72-hour period and marijuana during the previous 42 days.
Sample size and power calculations
We calculated the sample size needed to detect this effect size with 80% power and a two-sided significance level of 0.05. Assuming alpha = 0.05, beta = 0.20, a compound symmetry true correlation structure of 0.5 (the most conservative, based on our results from the earlier study [48], constant intervention effects during intervention and then during post-intervention, the maximum attrition rate of 35%, and 2:1 randomization, the sample size required was estimated to be 149.
Planned statistical analyses
Statistical testing and modeling will be conducted for each outcome discussed. All p-values will result from two-tailed tests, and a p-value < 0.05 will be considered significant. Data from this randomized controlled trial of DAART versus SAT among released prisoners will be analyzed using both an intent-to-treat analysis (including all subjects randomized into either one of the two arms) and an on-treatment analysis (including only those subjects who participated in the arm to which they were assigned). Comparison of baseline characteristics will be evaluated using the Mantel-Haenszel chi-square test for categorical variables and F test of analysis of variance for continuous scale data. Kruskal-Wallis testing and a Dunn multiple comparison test will be performed to determine any statistically significant changes observed in HIV-1 RNA levels (VL) and CD4 lymphocyte counts. Final linear regression models will incorporate covariates with a univariate outcome p<.10. The primary outcome is having a VL<400 copies/mL at 6 months, assessed using a Cox proportional hazards model with secondary variables as covariates. The secondary outcome is VL<50 copies/mL. Change in log10 HIV-1 RNA from baseline to specified time-related outcomes (e.g. 12, 24, 48 weeks) will be analyzed using Buckley-James distribution-free model, which accounts for censored data. Analysis of change in mean CD4 lymphocyte count from baseline to time endpoints will be performed using the Wilcoxon rank test, stratified by daily vs. twice daily antiretroviral regimen. Spearman’s rank correlation (ro) will be used to test for associations between data with a binomial (bimodal) distribution (i.e. adherence, VL, CD4 count with binary outcome). The same test will be used to assess the correlation between self-reported adherence to treatment and MEMS cap data. Pill counts will be used to verify the MEMS cap data and improve the model fit in comparison with self-report. Sensitivity analysis of different adherence measures (e.g. MEMS, VAS) will be incorporated.
Screening and baseline interviews occurred between January 2005 and December 2009. A total of 277 participants were referred, most of which (92%) came directly from the Connecticut Department of Correction (CTDOC). Of these, 202 were eligible and 154 enrolled in the study (Figure 1). The main reasons for exclusion or not enrolling was not planning to return to either New Haven or Hartford. This occurred primarily because inmates were either offered a relocation program before release or it was stipulated as part of their community re-entry program. Lack of interest in enrolling in the study was related to either not being interested in research in general or not being interested in an adherence intervention (or both). Though not captured systematically, these individuals either felt that their adherence was not a problem or that they did not have an interest in being involved in a research study (data not shown). Table 2 illustrates the baseline characteristics of the participants.
Figure 1
Figure 1
Flow chart of study recruitment, enrollment and completion.
Table 2
Table 2
Baseline characteristics of CONNECT study samples, N (%) for categorical variables and mean ± SD for continuous variables
DAART, compared to SAT subjects were similar with regard to demographic characteristics, social instability upon release, addiction severity and a number of other characteristics. DAART subjects were statistically more likely, however, to have a higher mean CES-D score, but did not differ from SAT subjects with regard to meeting criteria for depression using standard cut-off with the CES-D and mean QIDS-SR score. Similarly, the two groups did not differ in terms of type of ART regimen or baseline viral load or CD4 lymphocyte status. Thus, subjects were generally well-balanced.
HIV-infected prisoners have many unmet and challenging needs as they transition from the correctional to the community setting. Examples include homelessness, lack of social support, unemployment, and poor access to antiretroviral medications, medical care, psychiatric services or substance abuse treatment.[10, 14] It is clear that case management alone is sufficient to optimize HIV treatment outcomes after release from prison.[10, 18] Innovative community-based programs that make regular contacts with drug users (e.g., drug treatment, prisons, and needle exchange programs) have had an important place in the detection and successful treatment of TB and other infectious diseases among these high-risk individuals [49, 50]. Although transitional case management programs have improved linkage to care in the community, for some jail and prison release programs [51, 52] they have unfortunately not demonstrated benefit in regards to HIV treatment outcomes upon release from prison [53].
Released inmates are vulnerable to resuming risky sexual and injection-related behaviors [15, 54, 55]. Both idealized modeling [56] and empiric data [57] suggest that high levels of adherence and suppression of HIV replication can markedly reduce HIV transmission. Thus, it is imperative that the high levels of viral suppression that are achieved during incarceration persist after release to the community. Empiric data, however, suggest that the period immediately after release from prison is associated with increased morbidity and mortality, particularly from drug overdose and relapse and from HIV-related complications.[15] This is particularly true for sustaining HIV suppression [10, 13]. A number of factors may contribute to poor HIV-related incomes, including those amenable to intervention [58], including poor prescription refills, potentially associated with decreased access to antiretroviral therapy [16], relapse to drug use [17] and non-adherence and/or non-persistence to antiretroviral treatment [59].
Directly observed therapy (DOT) has been proven effective in the public health management of tuberculosis [60]. In contrast to tuberculosis treatment, however, HIV treatment is chronic and characterized by lifelong medication use and sometimes the need to dose medications more than once-daily, which poses obstacles to the implementation of DAART [61]. Evidence suggests, however, that DAART provides virological and immunological benefits to drug-using populations during the period of the intervention [20, 21, 62-68]. Furthermore, these benefits are conferred without producing higher rates of antiretroviral drug resistance [25, 69]. DAART is thus emerging as a critical tool for improving outcomes in vulnerable populations such as recently released HIV-infected inmates.
In a recent systematic review of DAART, however, Ford et al [70] concluded that directly observed antiretroviral therapy offers no benefit over self-administered treatment, and called into question the use of such an approach to support adherence in general patient populations. On the other hand, the same review did mention marginal benefit of directly observed therapy in groups that were judged to be at high risk of non-adherence [70] and two subsequent meta-analysis confirmed the benefits of DAART, especially among HIV-infected persons with substance use disorders [69, 71]. There is an ongoing debate on DAART benefits, with DAART proponents pointing out that it should not be implemented on patients without known problematic adherence and that trials of DAART should focus only on patients who are likely to derive benefit [72].
Resisting drug relapse is another tremendous challenge for released prisoners. 85% of released prisoners relapse to opioid and alcohol use upon release to the community, regardless of the time of incarceration [73, 74]. Active opioid use has been found to be highly associated with non-adherence to antiretroviral therapy and increases morbidity and mortality as well as increased risk-taking behaviors [75-77]. Medication-assisted therapy (MAT), including methadone, buprenorphine and extended released naltrexone (XR-NTX) therapy for opioid dependence and XR-NTX for alcohol use disorders [78, 79], is another measure which can help decrease drug and alcohol use, time to relapse, criminal activity and HIV risk behaviors and increase retention in treatment [80-83]. Future prisoner-release interventions should include MAT part of a comprehensive intervention to improve ART adherence and HIV treatment outcomes [58].
Findings from this study will answer many important questions. First, does DAART confer more benefit than standard of care in maintaining the benefits of ART conferred during incarceration. Second, can the benefits of DAART be maintained beyond the intervention period? Third, can the use of buprenorphine for the subset of subjects who meet criteria for opioid dependence improve outcomes with or without the added contribution of DAART? Fourth, are there other covariates that contribute to improved (e.g. MAT) or worsened outcomes (e.g. alcohol use or untreated psychiatric conditions that are highly prevalent in this population) that must be simultaneously addressed. Fifth, with newer ART regimens, does DAART promote or retard development of resistance to ART? Last, can DAART confer protection for HIV transmission despite prevalent HIV risk behaviors after release to the community? Until such questions are answered, it is imperative to utilize the best evidence available to create effective prison-release interventions for people living with HIV/AIDS.
Footnotes
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