Self-reported antiretroviral therapy adherence and viral load in criminal justice-involved populations

A high level of adherence to antiretroviral treatment (ART) is essential for achieving viral suppression among people living with HIV, and is critical for both maintaining their health and preventing HIV transmission to others. Valid, yet practical measures of adherence to ART are needed for studies of intervention efficacy and effectiveness in low-resource settings, and are useful for the clinical care of hard-to-reach populations who have extensive barriers to achieving viral suppression. Real-world, self-reported ART adherence measures that are reliably associated with viral load (VL) measures provide many advantages over medication event monitoring system (MEMS) or pill count, namely increased feasibility of use in busy clinical care settings where pill counts and MEMS have numerous logistical hurdles for routine use, as well as lower costs and more complete data [1, 2]. Self-report data, however, often underestimate real-world adherence and are susceptible to recall and social desirability bias [3, 4]. These weaknesses may be particularly problematic among those with substance use disorders, mental illness, low income or lower education/literacy levels, and/or unstable housing, which are common among criminal justice-involved persons [5‐9].

As 1 in 7 people living with HIV cycle through criminal justice settings each year [10], clinicians may benefit from self-reported ART adherence measures that correlate well with viral suppression among the criminal justice-involved persons they may treat. In this population, frequent measurement of VL is challenging, especially among those recently released from criminal justice settings who often are out of clinical care [5, 7, 8, 11]. Self-reported adherence is an important and practical tool to use in HIV care or interventions that help patients to attain VS. It can be used to identify adherence challenges early, before virologic failure is detected using VL testing. Few, if any, previous studies have examined the association of self-reported adherence with plasma VL among criminal justice-involved persons in multiple U.S. sites.

One of the most widely used measures of self-reported adherence is a single-item, 0–100% rating scale, generally called the visual analogue scale (VAS) [12, 13]. It has the advantages of brevity, ease of administration even among low literacy populations, and ease of interpretation. In usual care settings, evidence supports the validity of VAS for measuring ART adherence, and its practicality compared with longer self-report measures or with more objective measures – such as MEMS Caps or unannounced pill counts (UPC) [14‐16]. This single-item assessment is also easier and briefer than other self-report measures [13]. The VAS adherence measure has been shown to be associated with MEMS Caps, UPC, and viral suppression in some studies [4, 17], but has not been examined across studies of criminal justice-involved populations in need of HIV care.

Although several factors besides ART adherence can affect viral suppression including persistence on ART [18], genotypic resistance to ART [19, 20], and pharmacokinetics of ART medications [21‐23], self-reported adherence should be closely associated with VL level, and very high adherence (> 95%) should predict VS. [20] Also, the degree of correspondence between the adherence measure and VL might vary, depending on clinical factors, such as level of immunosuppression measured by CD4 count and level of self-reported general health status [24]. Little is known, however, about how well self-reported ART adherence measures perform in terms of its association with VL and levels of viral suppression in criminal justice-involved populations.

This study had two main goals. First, we sought to examine rates of ART adherence and viral suppression among criminal justice-involved people living with HIV across seven sites in the U.S. Second; we aimed to examine the association between self-reported ART adherence and VL. Additionally, we explored whether the relationship between adherence and VL was modified by level of CD4 count or self-reported general health status. We hypothesized that higher levels of self-reported ART adherence would be associated with lower levels of VL or with viral suppression (VL < 200 copies/mL) [25]. In addition, we hypothesized that the association between adherence and VL would be stronger among those reporting worse health or having later stage disease (lower CD4 count) because patients with more advanced disease or who have symptomatic HIV are more likely to both non-adhere to ART and have high plasma HIV RNA levels [26, 27]. To address these goals, we examined associations between ART adherence as measured by the VAS and plasma VL level, using harmonized data from multiple criminal justice-involved studies across the U.S. [28]. To provide a normative comparison group, we examined corresponding measures and associations among people living with HIV in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort of people living with HIV in routine, ambulatory clinical care across multiple sites in the US.

Among criminal justice-involved persons living with HIV from seven criminal justice-focused studies in STTR, we found consistent associations between higher self-reported ART adherence, using a variety of approaches, with lower VL levels. We compared these findings to people living with HIV in routine clinical care from seven CNICS sites across the US and found similar patterns of association. In addition, the coefficients reflecting the strength of the association were generally in the same direction and of similar magnitude to those among people living with HIV in the routine clinical care sample. These findings have important implications for the care of people living with HIV who cycle through criminal justice settings, and the study of ART adherence in the continuum of HIV care among criminal justice-involved populations. Because criminal justice-involved populations, particularly those recently released from incarceration, are highly transient and hard-to-reach because of frequent unstable housing, substance use, and mental health problems they face greater challenges to ART adherence as well as to accessing HIV care [35‐37]. Suitably, the findings support the use of a simple, VAS measure to assess self-reported ART adherence in criminal justice-involved populations. Its brevity, ease of administration, and interpretation make it attractive for use with low literacy populations such as the criminal justice-involved people living with HIV [13].

Of particular note, in the criminal justice sample we found that the associations of self-reported adherence with VL were robust in that there was a significant association of high levels of adherence with lower levels of VL, measured in a variety of ways – continuous (log-VL) and dichotomous. It is clinically useful to know that every 10-point increment on the 0–100% adherence scale is associated with approximately a 25–30% decrement in log-VL. The GAM analysis suggests that this association was not significantly different in magnitude at the low or high end of the VAS adherence scale. Together these findings mean that assessing self-reported ART adherence could be useful in detecting patients who are most likely to have uncontrolled viremia at the low end, as well as in detecting those who are likely well controlled at the high end of adherence reports. Comparisons of these associations with the routine care sample provided strong confirmation of the findings in the smaller criminal justice sample because in almost every analysis, the coefficients were of very similar direction and magnitude as those in routine care.

The examination of potential effect modification by CD4 cell count and general health status also enhanced the clinical relevance of our findings. In the criminal justice sample, the regression coefficients relating high levels of ART adherence with lower levels of VL were significant in both strata of CD4 count, and the interaction testing difference in the association by CD4 level was not significant, suggesting that the relationship held regardless of stage of illness. However, the point-estimate of this regression coefficient among those with CD4 level < 500 was twice as large as that among those with CD4 level ≥ 500. Furthermore in the routine care sample, the point-estimate of this regression coefficient among those with CD4 level < 500 was more than three times as large as that among those with CD4 level ≥ 500. Thus, with the large sample size the interaction testing differences in the association by CD4 level was highly significant. It is important that the association was strongest among those with the most advanced disease, and for whom clinicians would be most concerned. Nonetheless, the regression coefficients relating high levels of ART adherence with lower levels of VL were significant in both strata of CD4 count in the routine clinical care sample, supporting the robustness of the association.

Examination of the associations by self-reported general health status, however, did reveal more variation. Among the criminal justice sample, we found that the regression coefficients relating high levels of ART adherence with lower levels of VL was strong and highly significant among those with low self-reported general health status levels. However, the corresponding coefficient was quite weak (nearly zero) and non-significant among those with high self-reported health status levels. Thus, the interaction testing of the difference in the association by self-reported general health status level was highly significant. This finding supports the association among the most symptomatic, but not among those in best self-perceived health. Interestingly, the same pattern was not observed in the routine care sample. There we found the association of VAS adherence with VL was significant and of similar magnitude regardless of self-reported general health status levels, so the interaction was not significant. Moreover, we found that adherence was associated with viral suppression, especially for combination ART medications.

As with all studies, these analyses had several limitations. First, this study was cross-sectional and hence we can only report associations and cannot demonstrate causality. We restricted the criminal justice and routine clinical care samples to only those whose 30-day adherence report window covered the VL test date. While this restriction reduced the sample size substantially, whether the VL overlapped with the adherence timeframe would most likely impart random error, rather than systematic bias in one consistent direction. Inherent to smaller sample size is the reduced power of some analyses, especially the interaction or moderation analyses, such as those we conducted by CD4 and self-reported general health status. As often occurs with secondary data analyses, the data were collected for other purposes and hence did not always align with the design needs of this analysis. The smaller sample size resulting from our attempts to eliminate error reduced our power to detect associations and interactions, widening confidence intervals around the coefficients of associations. The sample size was also smaller for analysis by CD4 count and general health status than that for other variables, so we had limited power for these moderation analyses. We lacked data on barriers to adherence, or objective measures such as MEMs, pill count or number of pills in each ART regimen to make comparisons with the VAS. Despite these limitations in the data we do have viral load data that a strong anchor for adherence for this analysis. Last, although this study includes several major HIV epicenters around the US, and both jail and prison settings, the findings may not generalize to all criminal justice settings, nor to all major metropolitan or smaller areas. It also may not generalize to cases where the time frames of the VAS adherence and VL measures do not match.

Overall, we found that relationships between adherence and VL, using a variety of approaches among criminal justice-involved PLWH, were robust and similar to those in routine clinical care. Consequently, the VAS adherence measure is a convenient, valid and useful adherence measure to support treatment for criminal justice-involved people living with HIV who are vulnerable to falling out of care. While we recognize that obtaining VL is essential to assessing the outcomes of care, the VAS adherence measure is useful to clinicians in this situation, where it is often difficult to measure VL regularly. It can provide results more quickly and efficiently for clinical decision-making than more complex adherence measures, or VL tests which often take days to produce results. Findings from this assessment when adherence is suboptimal (<=95%) can direct clinical care in two important ways: 1) providers can quickly intervene to optimize adherence and possibly avoid virologic failure sooner than they could if they waited for VL test results and 2) proactively order HIV-1 genotyping to assess for virologic resistance to current medications. The latter is indicated because the risk of resistance is greater with poor or intermittent adherence that often attends criminal justice-involved people living with HIV who have prevalent substance use disorders and cycles of incarceration and release. This study also provides further evidence of the validity of the VAS adherence measure for use in other survey research. This is, particularly the case in post-release criminal justice-involved populations or other situations where more objective forms of adherence measurement and more frequent VL testing are not feasible. While some research has supported the notion that criminal justice-involved populations can achieve HIV continuum of care milestones as well as those of non-criminal justice-involved populations [38], it is generally recognized that criminal justice-involved populations are at particular risk of lacking HIV care and adherence to ART [7, 39‐41]. Gaps in care and loss of viral control often occur after release, when it would be impractical and cost-prohibitive to measure VL frequently or to monitor adherence with resource-intensive approaches, such as MEMS-caps [42, 43]. Thus, our finding that the magnitude of association between adherence to ART and VL was quite comparable to that in a sample of people living with HIV in routine clinical care was reassuring of the usefulness and robustness of the VAS adherence measure for use in other low resource settings. Future research should further examine the performance of adherence measures in additional hard-to-reach, disadvantaged populations.