Cohort profile: seek, test, treat and retain United States criminal justice cohort

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.


STTR treatment cascade
The Seek, Test, Treat and Retain (STTR) treatment or HIV care cascade is a challenging yet potentially beneficial response to addressing HIV in an era of effective treatments [1][2][3]. This approach requires reaching out to at-risk individuals who have not been tested for HIV recently (Seek), engaging them in HIV testing (Test), initiating persons living with HIV (PLWH) on antiretroviral therapy (ART) and other treatment services (Treat), and facilitating uninterrupted HIV care (Retain) [1,2]. The STTR treatment cascade provides a framework for research aimed at improving the delivery of services, care and outcomes of PLWH. There is substantial dropout across each cascade step, and it has been estimated that only~19% of PLWH in the United States (US) are aware of their HIV diagnosis, engaged in care, on ART, and have an undetectable viral load (VL) [1], although more recent numbers suggest improvements [4,5]. 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. Improvements in the STTR treatment cascade have the potential to benefit the health of PLWH and improve public health by reducing HIV transmission [2].
The relevance of understanding the STTR treatment cascade across all CJ settings In the US, there are two main types of correctional facilities-jails, that typically are administered by city or county governments, and hold people awaiting trials or serving shorter sentences (generally under two years), and prisons that typically are administered by state and federal governments and hold people serving longer sentences or who have had their parole or probation revoked. Community supervision includes pretrial, probation and parole. Pretrial refers to people awaiting trial before receiving a criminal conviction or acquittal. Probation refers to adults who have been placed on supervision in the community, typically through local or state court systems; about half of individuals on probation also serve a short jail sentence. Parole refers to people who are released early from prison to serve the remaining part of their sentence in the community [6]. The criminal histories of people in prison typically are more serious, lengthy, and varied than individuals in jail or on community supervision [7,8].
Currently, >95% of incarcerated individuals will be released and re-enter society with nearly 80% being released to parole supervision [9]. About 1 in 35 adults in the U.S. are under CJ supervision, and the number is expected to continue to increase [10]. This trend expands opportunities for HIV prevention and treatment, especially in the public health realm [11]. Specifically, the estimated HIV prevalence among individuals incarcerated in the US prison system is 2-3 times higher than the general population [12][13][14][15][16]. These statistics translate to one in seven PLWH being incarcerated each year, a figure that rises to one in five PLWH who are African-American or Hispanic [17]. Although HIV testing rates in federal and state prisons are generally high (71%), [18,19] testing rates in jails are not (19%) [18]. Because many CJ-involved individuals pass only through jail, it is likely that many who are infected will not be offered HIV testing [18,20]. These individuals may not know their HIV status or their potential to transmit HIV [21]. Lack of testing among this higher risk group, and early ART initiation for those who are infected, is a lost opportunity to improve individual and public health and decrease HIV transmission. Those with HIV who return to the communities where they may lack access to health care services, including screening and early diagnosis, are likely to receive HIV treatment only after the disease has progressed to advanced stages [16,22]. As such, the Centers for Disease Control and Prevention (CDC) encourages more frequent HIV testing of persons within the CJ system, particularly those with drug-dependencies, because PLWH who learn their HIV status are less likely to spread HIV and more likely to seek medical treatment that can lower the potential for HIV transmission and reduce HIV-associated morbidity and mortality [23,24]. Finally, while PLWH incarcerated in prisons have access to care, including ART, maintaining ART and other medical services is a significant challenge for many re-entering the community following incarceration in prison [25] and engagement in the HIV care cascade has been shown to decline substantially after release [26]. Effective interventions are essential to link individuals to appropriate post-incarceration care and enhance retention in HIV care. The CJ involvement makes this a particularly unique and important cohort for addressing key questions across the HIV treatment cascade.

Cohort development
The STTR CJ cohort is the product of the STTR Data Collection and Harmonization Initiative developed by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research (OAR). This cohort was developed by a collaboration with researchers who harmonized and pooled data from independent prospective research studies funded under a grant mechanism focused on enhancing the STTR treatment cascade for individuals involved with the CJ system across the US [27]. This initiative produced another cohort not described here focused on vulnerable populations particularly substance users at risk for or with HIV in international and domestic settings. While the STTR initiative and its rationale have been previously described [27], the cohort itself has not yet been described.

Cohort management structure
The STTR CJ collaboration consists of a three way partnership between 1) individual researcher teams responsible for conducting the STTR studies and overseeing all enrollment and data collection; 2) a scientific officer and program officials from NIAID, NIDA, NIMH, and OAR who provide expertise and guidance regarding the data harmonization initiative; and 3) the STTR Data Coordination Center (DCC), which provides expertise in data harmonization, epidemiology, biostatistics, and HIV, harmonizes the data, supports investigations that use the harmonized data to answer novel scientific questions, and develops new methods for analysis of complex pooled data.

Cohort description
The STTR CJ cohort is unique in its focus on data from individuals involved in the CJ system and includes 11 NIAID, NIDA, NIMH, and OAR funded studies, several of which involve multiple sub-components and embedded studies. It includes single and multi-site randomized controlled and observational trials evaluating interventions to enhance care delivery along the HIV treatment cascade. It provides a large sample across CJ settings (jail, prison, community supervision) and includes both PLWH and HIV-uninfected individuals, many of whom engage in illicit drug use. Compared to single studies, the CJ cohort data provide increased statistical power to determine public health benefits of the STTR paradigm, address research questions on specific groups at risk of exiting the treatment cascade, and improve understanding of the intersection of drug use and HIV treatment. This cohort profile describes data from the resulting cohort and individual CJ studies including baseline demographic and clinical characteristics.

Data harmonization
Eleven domains were selected for data harmonization: CJ involvement; HIV risk behaviors; HIV and/or hepatitis C infection; laboratory measures of CD4+ cell count and HIV RNA viral load among those with HIV; mental health; health related quality of life; socioeconomic; health care access; substance use and alcohol use; and social support (Fig. 1). The goal is to integrate data from across studies to address research questions requiring sample sizes beyond that of a single study.
The DCC, with investigators from individual studies, is responsible for data integration. The DCC provides technical support and oversees a web-based project collaboration and document management system; documents procedures for data collection and translation, transmission, and quality control; develops integration methods; and generates analyzable data sets. Studies typically upload data biannually. The DCC coordinates data integration from studies sometimes collected using different instruments or timeframes to ensure that the data are comparable across studies in meaning and content. To accomplish this, an examination of data types collected by each study was conducted, working closely with individual study personnel to survey each study's protocol including how data were collected and modifications to the instruments used. Where data were comparable, codes were developed to create standardized sets of variables.

Availability of data and materials
The datasets generated during the current study are not publically available due to privacy/license concerns. However, we welcome collaboration from interested parties. We have policies to ensure multi-center analytic research proposals are developed and results analyzed collaboratively and fairly. We are guided by principles of other cohort collaborations [28][29][30] including that data at the DCC will be stripped of all protected health information (PHI); an individual study can choose to participate or not in any scientific aim or sub-aim; and concept proposals and completed manuscripts must be approved by the Publications and Presentations (P&P) committee. We appreciate and encourage mentorship and the use of the STTR data to enable early investigators to address meaningful questions with support to help ensure their success. Additional information can be obtained at the STTR website: https://sttr-hiv.org/cms or by contacting the STTR DCC at STTR@uw.edu. Figure 2 shows the diverse geography of the participating studies. For each of the 11 studies and their substudies, the research topic, the components of the STTR treatment cascade addressed, and the targeted participants are described in Table 1. All the steps of the treatment cascade are included in multiple studies, and a diverse array of research topics are included. The STTR CJ cohort includes studies focused on later steps in the STTR treatment cascade such as treatment and retention of PLWH and studies focused on earlier steps such as HIV testing. Therefore, the percentage of PLWH in the individual STTR CJ studies at baseline varies, ranging from 0 to 100% (Table 1), with an overall baseline total of 1888 PLWH. For each of the 11 studies and their substudies, detailed inclusion and exclusion criteria, and the study design including whether it was observational or a trial is described in Table 2. In addition to baseline information, most studies collected data at 3 and/or 6month follow-up time points, and many include 12 month and other follow-up time points ( Table 2).

Description of the STTR CJ studies and participants
The STTR CJ cohort includes 11,070 individuals with and without HIV who range in age from 18 to 77 years with a median baseline age of 37 years. The STTR CJ cohort is diverse and includes substantial numbers of African-American (64%) and Hispanic (12%) individuals as well as 17% percent women (Table 3). Given differences in enrollment criteria across STTR CJ cohort studies, the percentage reporting HIV risk behaviors varies considerably (Table  4). Injection drug use (IDU) ranged from 86% of participants reporting ever use in one study, with 64% in that study reporting IDU within the 30 days prior to incarceration, to very low levels in other studies ( Table 4). Reports of recent condomless anal or vaginal intercourse also varied from 4 to 79% of participants. Recent use of marijuana, cocaine, and opioids, and binge drinking were common across all studies (Table 5) with 53% reporting use of multiple substances. Information regarding nonmedical prescriptions drug use is available from 9 of the studies and substudies. The participants were recruited from a wide range of CJ settings including jail, prison, and community supervision (pretrial, parole and probation) with particularly large numbers of individuals from jail, prison, and probation (Table 6).

Harmonization results
By combining data across multiple studies, we include individuals involved with varying aspects of the CJ system, enabling comparisons that cannot typically be done within individual studies. For example, harmonizing data enables analyses involving subgroups such as transgender individuals and other subgroups that are often too small to assess in individual studies.
A key finding from our conduct of data harmonization is the need for multiple approaches. One technique involved modern psychometric approaches such as item response theory (IRT) to co-calibrate scales. Co-calibration enables    Table 1 b There are 33 participants who are included in more than one sub-study: 3 in BRIGHT 1 and BRIGHT 2, and 30 in UHSIIC and UHSIIL people from studies who responded to different instruments to have scores that are "calibrated together" on a single common metric. IRT provides a suite of tools to model and account for measurement precision. We use this approach to address differences in the depression and anxiety measures across studies. In contrast, we found a different approach was needed to harmonize domains like ART adherence, which are behavioral rather than latent traits. Below we describe two harmonization efforts for ART adherence and risk behaviors.

Harmonization of ART adherence measures
We used CJ studies that measured ART adherence with both the AIDS Clinical Trials Group (ACTG) questionnaire and the Visual Analogue Scale (VAS) measure to develop rules and a formula to co-calibrate both instruments. By co-calibrating adherence items from the ACTG (7 day recall) with the VAS, we were able to harmonize studies having different approaches to measuring adherence [31]. We found that 44% of PLWH in the STTR CJ cohort who were on ART reported adherence rates <95% for the prior 30 days and 38% reported having missed one or more doses in the prior 14 days. Furthermore, we found important variations not only in ART adherence in different groups, but also in how adherence measures work. The findings also highlighted problems with the VAS as a single item adherence measure and showed its validity varied across groups. These results would not have been feasible within single studies but instead were possible by harmonizing multiple studies to gain both necessary sample size and variation [32].

HIV sexual risk behavior harmonization
Eight studies administered a standardized risk behavior assessment tool to evaluate sexual risk behaviors in these reference periods: 30 or 90 days prior to incarceration for jail and prison detainees, or the previous 30 or 90 days for participants enrolled in the community. We described sexual risk behaviors of HIV-infected and uninfected participants in these studies and compared men and women [33,34]. To test for differences in risk behaviors between men and women, we performed individual patient data meta-analysis to combine information across studies. Findings indicated a high prevalence of condomless anal or vaginal sex among PLWH and uninfected participants, particularly women with HIV. For example, the adjusted odds ratio for condomless sex was 1.84 (1.16-2.95) for women with HIV compared with men with HIV [34]. By aggregating data across studies, we were able to overcome the much lower prevalence of women in CJ populations and, in turn, in each of the individual CJ studies.

Discussion
STTR CJ is a unique cohort that combines data from 11 studies that together address steps across the HIV treatment cascade focusing on participants with CJ involvement. The STTR CJ cohort includes a large and diverse assemblage of individuals who are at risk for, or living with HIV. The pooled data cohort is a sample of men, women, and transgender individuals across different racial/ethnic groups in multiple CJ settings (prison, jail, pre-trial, community supervision) as well as participants with no CJ involvement. The intervention studies span the HIV treatment cascade and have broad geographic locations across the US with participants enrolled from 11 states and the District of Columbia. These characteristics provide the opportunity to address questions of great importance for HIV prevention and treatment particularly related to individuals involved in the CJ system, those at risk or with HIV and using substances, and the unique risks and clinical needs of specific subgroups. For example, we are particularly interested in understanding the impact of changes in the intensity of substance use on HIV care cascade outcomes such as viral suppression and adherence, the impact of incarceration and release on the HIV care continuum, and to better understand risk behaviors of individuals upon release from incarceration. Finally, the study investigators and DCC have expertise in clinical, epidemiologic, CJ, biostatistical, and data harmonization areas. This team is well-positioned to address transdisciplinary scientific questions and identify new questions that will arise as HIV care and prevention continues to evolve, and we have developed harmonized measures to allow for combining studies to answer these questions.
There are limitations to the STTR CJ cohort data. Some of these limitations are inherent in combining data from independent studies with different enrollment criteria and different study designs. While the STTR CJ cohort includes a large number of CJ-involved PLWH or persons at risk of HIV, this combination of studies is not a representative sample of those involved in the CJ system in the US, and in particular may underrepresent   When merging these studies it is critical to identify the subset of the STTR CJ cohort appropriate for and able to provide data on the research questions of interest. These studies recruited from diverse source populations. For example, two studies recruited participants who were at high risk of CJ system involvement but not necessarily already involved with the CJ system at baseline. This variation prevents the naïve pooling of studies, as baseline characteristics are different between studies, and requires clustering of participants by study be accounted for using a mixed model or generalized estimating equation approach. Longitudinal follow-up duration and frequency varies with several studies having limited follow-up time although we will continue to include all additional data collected over follow-up, so long as studies remain ongoing. While this variation limits power for analyses looking at longitudinal outcomes, the STTR CJ cohort remains better powered than individual studies. The STTR CJ cohort is designed to allow expansion for new studies and domains as needed to address important questions in the HIV research agenda particularly related to the STTR treatment cascade. New studies will be added as needed to increase demographic, geographic, or clinical diversity and broaden scientific expertise. The STTR CJ cohort welcomes collaboration from interested parties and has policies to ensure multicenter analytic research proposals are developed and results analyzed collaboratively and fairly.

Conclusions
This cohort provides a large study sample across different CJ settings (jail, prison, community supervision) and includes both persons with and without HIV, many of whom engage in illicit drug use. Compared to single studies, the combined data of the CJ cohort provides increased statistical power to determine the public health benefit of the STTR paradigm, address research questions on specific groups at risk of exiting the treatment cascade, and improve understanding of the intersection of drug use and HIV treatment.