Simple, Effective Interventions Are Key to Improving Adherence in Marginalized Populations

To assist any marginalized population in poor health, we require simple, effective interventions that are pragmatically accessible. In this issue of Clinical Infectious Diseases, Petersen et al. [1] demonstrate an important association between pillbox use and both improved adherence and decreased HIV load. Considering the low cost and simplicity of this intervention, it represents an important tool to assist patients with HIV infection who are on the threshold of adequate adherence to maximize the potential outcomes possible with their daily combination antiretroviral regimens. There are currently few easily applied interventions with proven effectiveness in improving adherence [2]. Despite the plethora of interventions evaluated, ranging from toolkits and psychological counselling to cellular telephone text messages, many of these interventions have poor effectiveness, are difficult to apply broadly, and are expensive. Many marginalized populations living with HIV infection or AIDS, such as drug users, the homeless, and those with mental illness, are unable to access consistent, human resource–based interventions [3]. Challenges for these populations include forgetfulness, drug-induced apathy, stigma, and a lack of interest in time-consuming interventions that require interactions with health care staff. Although the barriers to adequate adherence in these populations are well-known, facilitators to improving adherence are less well understood [3]. For this reason, the contribution by Petersen et al. [1] provides an important step towards providing pragmatic assistance to marginalized people living with HIV infection or AIDS. The usefulness of pillboxes in treating chronic diseases is not new, and previous meta-analyses of randomized trials involving other conditions have demonstrated their effectiveness [4]. So why has it taken so long to evaluate their role in treating HIV infection and AIDS? Rather than looking towards simple interventions that patients can understand and access, the traditional focus of adherence research has been directed towards expensive and human resource–intensive interventions [2]. For example, directly observed therapy with antiretroviral drugs is now being disseminated widely among marginalized populations in North America and elsewhere. However, the success of this intervention remains in question [5]; it is comparatively expensive, and it may be associated with negative psychosocial outcomes. It seems obvious that, before resource-intensive interventions are initiated, we should first try simple and accessible strategies. This study [1] demonstrates, using a complex analysis of the San Francisco cohort, further strong inferences about the causative relationship between a simple intervention (i.e., pillboxes) and improved adherence. We recognize that evaluating adherence is a challenge in any population and that there is no gold standard for evaluating adherence. Petersen et al. [1] used unplanned pill counts as the primary outcomes, a strategy that provides strong inferences about the number of pills taken prior to the pill count. This strategy is superior to more-complex measurement tools, such as electronic bottle caps and pharmacy refills, because it removes research environment–driven biases and eliminates the patient's knowledge of how many pills to return to the pharmacy [6]. However, the study is not without bias. The willingness of patients to use pillboxes may be a marker of increased desire to take antiretroviral therapy. To the benefit of this analysis, the group reinforced their assessment of adherence by examining its relationship with the clinically important end point of plasma HIV load (albeit with a cutoff point of 400 copies/mL, which is higher than what is considered to be optimal by today's standards). Nevertheless, although neither end point alone is proof of causation, the combined relationship observed by Petersen et al. [1] is persuasive evidence that this low-cost intervention improves clinical outcomes. The findings of Petersen et al. [1] indicate that this intervention increases adherence by 4%–5%. Although, at first glance, this seems like an outcome that will produce only benefit, the true impact on immediate and long-term HIV load suppression may be dependent on the patient's baseline level of adherence. For the occasionally nonadherent patient (e.g., one who takes 90% of the prescribed mediations, with a missed dose every 1–2 weeks), the pillbox intervention may have a fundamentally beneficial impact on preventing the development of antiretroviral drug resistance by reducing, if not eliminating, periods during which wild-type HIV is exposed to subtherapeutic plasma antiretroviral levels. The impact on those patients with much poorer levels of adherence is uncertain. For some, provision of medications by pillbox may provide the amount of structure and routine needed to transform an occasional user of antiretroviral drugs into one who achieves the 95% level of adherence needed to achieve durable virologic suppression and avoid drug resistance evolution [7]. One undesirable but plausible outcome is that a 5% improvement in adherence may shift a patient from maintaining drug levels that are too low to generate drug resistance to a subtherapeutic plasma antiretroviral level that is insufficient to fully suppress HIV but is high enough to provide sufficient pressure to produce drug resistance. This may be an issue of particular relevance with respect to protease inhibitor–based treatment [8]. Despite this theoretical concern, the reality is that suboptimal adherence is a major hurdle to achieving success with HIV therapy, and few effective interventions are available to correct this. However, the most important aspect of the study is not the novel methodology or the advanced statistical methods used, but that the authors asked an important, straightforward question and aimed to answer it in a sound manner [9]. Although the medical research world is promising tremendous improvements in health with advanced technologies, effective and accessible interventions are few and far between. Populations affected by drug use, homelessness, and mental illness are the least likely to access new technologies, and any interventions with monetary value will often be sold or lost within a short period. Assessing an intervention that costs <$5 and that can be used repeatedly over an extended period is not a particularly flashy approach to improving HIV infection and AIDS care. Pillboxes represent a pragmatic, user-friendly, and cost-effective approach to health care delivery that should be most welcome in these populations. Patients in marginalized populations are some of the hardest to treat effectively, and that is why we need to assess simple interventions that are culturally acceptable. Although we can dream up complex and expensive interventions, their applicability in these populations is questionable. Simple and effective interventions that are widely used can have a tremendous impact on the health of the population. Pillboxes appear to be one such simple and effective intervention and should be widely used. Financial support. Canadian Institutes for Health Research (to E.J.M.) and the Ontario HIV Treatment Network (to C.C.). Potential conflicts of interest. E.J.M. and C.C.: no conflicts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.