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Review Article

A Systematic Review of Nurse-Led Antiretroviral Medication Adherence Intervention Trials

How Nurses Have Advanced the Science

Lambert, Crystal Chapman PhD, CRNP, ACRN*; Galland, Brooke BS; Enriquez, Maithe PhD, APRN, FAAN; Reynolds, Nancy R. PhD, RN, ANP, FAAN

Author Information
Journal of the Association of Nurses in AIDS Care: May-June 2021 - Volume 32 - Issue 3 - p 347-372
doi: 10.1097/JNC.0000000000000247
  • Open


If antiretroviral (ART) medication is taken as prescribed, the once-fatal HIV infection is a chronic, manageable disease with a good prognosis (Deeks et al., 2013). The international HIV goal (95-95-95) aims for 95% of people living with HIV (PLWH) to know their HIV diagnosis, 95% of people diagnosed with HIV to be on ART, and 95% of people on ART to achieve viral suppression by 2030 (UNAIDS, 2014; UNGA, 2017). The primary clinical goal of HIV treatment is sustained suppression of viral load, which aligns with the public health priority of preventing HIV transmission in the community as the risk of transmitting HIV to another individual is eliminated by the use of fully effective ART medications among adherent individuals (DHHS, 2019). Despite the real and promising opportunity for a combined clinical and public health strategy to eradicate HIV from the community, the incidence of infection remains high and disparate, particularly among racial, ethnic, and sexual and gender minority populations, notwithstanding decades of work to reduce the spread of the HIV pandemic (Nash, 2020).

Public health workers have adopted a number of strategies, some quite successful, to suppress community HIV viral load and decrease disease transmission (Mohammed et al., 2018). Unfortunately, these widespread efforts to identify individuals with HIV infection, link them to care, and suppress viral load by treating with ART are much less effective than they could be. Subgroups of the populations living with HIV are not taking ART medications or are struggling with adherence to treatment and, hence, do not have a suppressed HIV viral load. This is continuing to fuel avoidable HIV transmission in many communities, resulting in negative health outcomes for many individuals living with HIV (Jeffries et al., 2018; Martinez et al., 2018; Trinh et al., 2017).

Unfortunately, despite efficacious, well-tolerated, and accessible HIV treatment options, adherence to antiretroviral therapy remains unsatisfactory and varies between 27% and 80% across different population groups in various studies globally (Iacob et al., 2017). Only about half of the people living with HIV in the United States have reached the universal goal of attaining a fully suppressed HIV viral load (Centers for Disease Control and Prevention [CDC], 2017). Untreated HIV infection, suboptimal medication adherence, and lack of viral load suppression results in a much higher risk of transmitting HIV to other individuals and developing HIV drug resistance with consequent treatment failure, thereby increasing morbidity and mortality (Crepaz et al., 2018). Suboptimal adherence to HIV treatment and lack of retention in HIV care remain vexing issues that are widely recognized as some of the most pressing challenges in treating HIV disease and ending the HIV epidemic (Stricker et al., 2014).

A number of critical studies have investigated the phenomenon of nonadherence to ART and developed strategies to enhance medication adherence (Amico et al., 2013; Chaiyachati et al., 2014; Kanters et al., 2017; Liu et al., 2013; Robbins et al., 2014). These interventions, delivered either singly or in combination with other interventions, have included counseling (e.g., cognitive behavioral, motivational interviewing, psychoeducational), directly observed therapy, financial incentives, reminder devices (such as mobile phone text messages), and peer and family support. There is robust evidence that the interventions can significantly improve ART adherence in some situations, but each intervention has also been found not to have a significant effect in others (Chaiyachati et al., 2014). Several intervention strategies have led to increased adherence rates as assessed by behavioral measures such as self-report or pill counts. However, the effect sizes have sometimes been small, measures of viral load suppression have not been used, or differences in viral load outcomes in comparison with the control condition were not significant (Enriquez & McKinsey, 2011; Spaan et al., 2020).

As the 40th commemoration of the HIV epidemic approaches, it remains critical to develop and use evidence-based strategies to enhance and support adherence to HIV treatment to improve individual and public health outcomes. Thus, the purpose of this review was to highlight the unique and significant contributions that nurses have made to advance the science surrounding effective HIV medication adherence interventions.


The Preferred Reporting Items for Systematic Review guided this review (Liberati et al., 2009; Moher et al., 2009, 2015).

Eligibility Criteria

Eligibility criteria were aligned with the purpose of this review to highlight the contributions of nurses in the advancement of HIV medication adherence interventions. Studies were included if they met the following eligibility criteria: (a) written in English; (b) a randomized controlled trial; (c) focused on HIV medication adherence as an outcome; (d) published in a peer-reviewed journal; (e) the intervention delivery was facilitated by a nurse; and (f) the study was published between January, 2006 to the end of December 2019. We set the year limit at years published between 2006 to the end of December 2019 to capture studies that examined interventions designed to promote adherence to contemporary ART regimens.

Information Sources and Search

The final search was performed on December 18, 2020 with the assistance of a librarian at the Johns Hopkins School of Nursing. To minimize the bias of missed published interventions, multiple search strategies were implemented (Figure 1). Studies were identified through systematic searches of electronic databases and scanning the reference lists of relevant articles. The data bases searched were PubMed, CINAHL, Embase, Cochrane, Web of Science, and Scopus. Multiple search terms were deployed, reflecting our eligibility criteria: antiretroviral (i.e., antiretroviral therapy, highly active, antiretroviral therapy, ART, HAART, retrovirus, anti-HIV agents); adherence (i.e., patient compliance, treatment refusal, adherence, noncompliance, nonadherence); randomized controlled trial (i.e., controlled clinical trial, allocated, controlled study, random assignment); and nurse (nurse, nurse-led, nurse-delivered).

Figure 1
Figure 1:
Flow diagram (Liberati et al., 2009; Moher et al., 2009, 2015) of inclusion and exclusion of publications. Note. RCT = randomized controlled trial.

Study Selection

Two authors (C.C.L. and B.G.) screened records initially by title and abstract for eligibility. All duplicate publications were excluded, as well as case reports and letters reporting study findings. All randomized controlled trials reporting results were included, even if they were pilot studies. The full-text documents that met the eligibility criteria or for which eligibility was unclear by the title and abstract review were then examined. Discrepancies regarding eligibility were resolved by discussion between the two reviewers (C.C.L. and B.G.), and if consensus could not be reached, a third author (N.R.R.) resolved the differences.

Data Collection Process and Data Items

Once the authors identified all eligible articles, one author (B.G.) extracted the data describing the study characteristics, including first author and date published, title, target population, sample size, country where study was conducted, characteristics of the intervention and control conditions, adherence measures and treatment effect (Table 1).

Table 1
Table 1:
Summary Study Characteristics

All extracted data were initially compiled in an Excel spreadsheet and then independently assessed by a second (C.C.L.) and third (N.R.R.) author. Any disagreements were resolved by discussion between all authors.


Using the search terms, 1,099 articles were identified. After removing duplicates, 726 articles were identified. A review of the abstracts and titles for appropriateness excluded 683 of these articles. Forty-four full-text articles were retrieved and screened and 21 were removed by application of the inclusion and exclusion criteria. A total of 23 articles were retained for data extraction (Figure 1).

Sample Characteristics

The 23 studies included in the review contained study samples that ranged in size from 20 to 2,172, and most (12/23) were conducted in the United States (Table 1). The other studies were conducted in China (Huang et al., 2013; Simoni et al., 2011; Wang et al., 2010; Williams et al., 2014), Estonia (Uuskula et al., 2018), Kenya (Lester et al., 2010; Sarna et al., 2008), the Netherlands (de Bruin, Hospers, et al., 2010; de Bruin et al., 2017), and Tanzania (Geldsetzer et al., 2017; Mugusi et al., 2009).

All study participants were adults 18 years of age or older. Studies enrolled participants who were either exclusively antiretroviral treatment-naive (8/23; Koenig et al., 2008; Lester et al., 2010; Mannheimer et al., 2006; Mugusi et al., 2009; Reynolds et al., 2008; Robbins et al., 2013; Sarna et al., 2008; Simoni et al., 2011), treatment-experienced (Berg et al., 2011; de Bruin, Viechtbauer, et al., 2010; Enriquez et al., 2015; Geldsetzer et al., 2017; Holzemer et al., 2006; Wang et al., 2010), or had a combination of both treatment-naive and treatment-experienced PLWH (Blank et al., 2014; de Bruin et al., 2017; DiIorio et al., 2008; Huang et al., 2013; Konkle-Parker et al., 2012; Uuskula et al., 2018; Wagner et al., 2006; Williams et al., 2014), and one study did not specify (Holstad et al., 2011). A few studies enrolled participants with other specific characteristics, including active or history of drug use (Berg et al., 2011; Uuskula et al., 2018; Wang et al., 2010; Williams et al., 2014), active mental illness (Blank et al., 2011), or female only (Holstad et al., 2011).

In studies that reported the sexual orientation or identity of their sample (de Bruin, Hospers, et al., 2010; de Bruin et al., 2017; DiIorio et al., 2008; Holstad et al., 2011; Koenig et al., 2008), most participants described themselves as heterosexual or straight (24–77.7%), homosexual or gay (2.6–70.0%), and some as bisexual (2–10%). Only one study reported transgender participants (2% of the sample; DiIorio et al., 2008; data not shown).

Treatment Groups

Most of the studies tested interventions that were delivered at the individual level (21/23). One of the interventions was delivered by group (Holstad et al., 2011), and one intervention was delivered at both the individual level and by group (Simoni et al., 2011). Seventeen of the interventions were fully or partially delivered by phone; three of these used SMS text messaging. Nine of the interventions used peer support and/or family support as a component of the intervention. All but one study (Sarna et al., 2008) used a form of psychosocial counseling such as cognitive behavioral therapy or motivational interviewing and provision of information to build knowledge, motivation, and skills (e.g., problem solving) to enhance adherence behavior. Four studies (Berg et al., 2011; Blank et al., 2011; Mugusi et al., 2009; Sarna et al., 2008) used directly observed therapy, and three used electronic monitoring feedback (de Bruin, Hospers, et al., 2010; de Bruin et al., 2017; Koenig et al., 2008) as the mechanism for fostering ART adherence. Nearly all the interventions used multiple component approaches. The interventions varied in length as well as frequency of delivery, and control groups most often received usual or standard care (see details in Table 1). Three studies used an enhanced usual care condition, and three used an attention control group (Enriquez et al., 2015; Holstad et al., 2011; Sarna et al., 2008; Table 1).

Each of the interventions was delivered in full, or in part, by a nurse. Most studies did not report why a nurse was used for delivery of the intervention. Likewise, most of the studies did not identify what level of educational preparation the nurse had or whether the nurse was expected to bring a certain set of competencies to the delivery of the intervention. Two of the studies (Blank et al., 2011; Konkle-Parker et al., 2012) specified that the intervention was delivered by an advanced practice nurse, and one indicated that the nurse held a Bachelor's of Science in Nursing degree (Simoni et al., 2011). Five of the studies indicated that Registered Nurses delivered the intervention (DiIorio et al., 2008; Huang et al., 2013; Reynolds et al., 2008; Wang et al., 2010; Williams et al., 2014). Others indicated that the study was delivered by clinic nurses (Berg et al., 2011; Enriquez et al., 2015; Koenig et al., 2008; Lester et al., 2010; Mugusi et al., 2009; Sarna et al., 2008; Simoni et al., 2011), study nurses (Holzemer et al., 2006; Mannheimer et al., 2006; Robbins et al., 2013; Uuskula et al., 2018; Wagner et al., 2006), or HIV clinic nurses (de Bruin, Hospers, et al., 2010; de Bruin et al., 2017). Several articles reported that the intervention nurse received training for delivery of the intervention as part of the study protocol. Eight of the studies were led by a nurse researcher, as noted in Table 1.

Adherence Measurement

Adherence was predominantly measured by self-report (14/23; Berg et al., 2011; Holzemer et al., 2006; Huang et al., 2013; Konkle-Parker et al., 2012; Lester et al., 2009; Mannheimer et al., 2006; Mugusi et al., 2009; Reynolds et al., 2008; Robbins et al., 2013; Sarna et al., 2008; Simoni et al., 2011; Uuskula et al., 2018; Wang et al., 2010; Williams et al., 2014), followed by an electronic monitoring device (10/23; Berg et al., 2011; de Bruin, Hospers, et al., 2010; de Bruin et al., 2017; DiIorio et al., 2008; Enriquez et al., 2015; Holstad et al., 2011; Holzemer et al., 2006; Koenig et al., 2008; Simoni et al., 2011; Wagner et al., 2006), and pill counts and/or pharmacy refill (4/23; Berg et al., 2011; Enriquez et al., 2015; Holzemer et al., 2006; Konkle-Parker et al., 2012). Self-report was usually measured by a 4-, 7-, or 30-day adherence recall. Two of the studies used a 0–100% visual analog scale (Konkle-Parker et al., 2012; Williams et al., 2014). Most of the studies collected HIV viral load (20/23; Berg et al., 2011; Blank et al., 2011; de Bruin, Hospers, et al., 2010; de Bruin et al., 2017; DiIorio et al., 2008; Enriquez et al., 2015; Geldsetzer et al., 2017; Holstad et al., 2011; Holzemer et al., 2006; Koenig et al., 2008; Konkle-Parker et al., 2012; Lester et al., 2009; Mannheimer et al., 2006; Reynolds et al., 2008; Robbins et al., 2013; Sarna et al., 2008; Simoni et al., 2011; Uuskula et al., 2018; Wagner et al., 2006; Williams et al., 2014) and CD4+ T-cell counts (16/23) through chart review or as part of the study protocol (Blank et al., 2011; de Bruin et al., 2017; DiIorio et al., 2008; Enriquez et al., 2015; Holstad et al., 2011; Holzemer et al., 2006; Huang et al., 2013; Koenig et al., 2008; Konkle-Parker et al., 2012; Mannheimer et al., 2006; Mugusi et al., 2009; Robbins et al., 2013; Sarna et al., 2008; Simoni et al., 2011; Wagner et al., 2006; Williams et al., 2014).

Adherence was measured at different intervals and over varying lengths of time (Table 1). A variety of different statistical approaches were used to summarize and analyze the data.

Adherence Outcomes

Among the studies (21/23) that measured adherence with a behavioral measure (self-report, an electronic measuring device, pill count, or pharmacy refill data), 12 of the studies (Berg et al., 2011; de Bruin, Hospers, et al., 2010; Enriquez et al., 2015; Koenig et al., 2008; Lester et al., 2010; Mannheimer et al., 2006; Reynolds et al., 2008; Sarna et al., 2008; Uuskula et al., 2018; Wagner et al., 2006; Wang et al., 2010; Williams et al., 2014) reported that the intervention group had significantly better adherence than the control group. Six of the 20 studies (Berg et al., 2011; de Bruin, Hospers, et al., 2010; de Bruin et al., 2017; Enriquez et al., 2015; Koenig et al., 2008; Lester et al., 2010) that reported viral load outcomes found that the intervention group had significantly better viral suppression outcomes than the control group. Others reported a trend toward better viral load outcomes (Blank et al., 2011; Holstad et al., 2011; Konkle-Parker et al., 2012; Mannheimer et al., 2006; Reynolds et al., 2008; Sarna et al., 2008).


There is a large, global base of evidence that supports the effectiveness of ART adherence interventions. Although contemporary ART regimens have more convenient dosing (e.g., single tablet, once-daily dosing) and are far better tolerated than older regimens, adherence to HIV medications continues to be a challenge to many PLWH. The purpose of this review was to examine the contributions of nurses to the science surrounding HIV medication adherence interventions designed to support better adherence. The interventions examined in the 23 studies included in this review were delivered, at least in part, by nurses. Eight of the studies were led by nurse researchers.

Many of the studies reported that the nurse-delivered HIV medication ART adherence intervention had a positive effect on adherence or HIV viral outcomes or both. However, some studies were not powered to examine significance and reported only a trend toward viral suppression, and the majority used the standard of care as the control group intervention rather than a time- and contact-matched attention control group. Nonetheless, these results suggest that nurses can provide effective delivery of ART adherence intervention content through various modalities (e.g., individual-level face-to-face or phone, group). However, similar to the broader ART adherence intervention literature, which shows that adherence interventions can significantly increase ART adherence in some settings (Amico et al., 2013; Chaiyachati et al., 2014; Kanters et al., 2017; Liu et al., 2013; Robbins et al., 2014), the effect is inconsistent. Further, there was a great deal of heterogeneity of study designs and methodologies. As such, it is difficult to assess whether the variance in the nurse-delivered adherence intervention study outcomes is due to the intervention content, the target population, characteristics of the interventionist, or the measurements and analytic approach used.

Most of the interventions included in this review focused at the individual level. This delivery format is consistent with the U.S. Centers for Disease Control and Prevention's medication adherence evidence-based behavioral interventions that are focused at the individual level and are not multilevel interventions (Centers for Disease Control and Prevention, 2020). Yet, community and social–structural level interventions are essential to ending the HIV epidemic because factors such as stigma and discrimination are salient factors that influence the HIV epidemic from prevention to treatment (Cahill et al., 2017; Katz et al., 2013; Relf et al., 2019). In fact, one of the key areas for HIV funding is addressing multilevel factors that influence HIV prevention and treatment (The National Institute of Health, 2020). To effectively address stigma and discrimination as barriers to ART adherence, future interventions should focus beyond the individual level (Agurs-Collins et al., 2019).

Nurses are known to play a vital role in HIV care, from prevention to medication adherence to viral suppression (Dumitru et al., 2017; Rouleau et al., 2019; Tunnicliff et al., 2013). Although each of the studies reviewed used nurses to deliver the intervention, many did not report a rationale for employing nurses to deliver the interventions or specify competencies expected of the nurse interventionists. Moreover, in addition to being known as the most trusted profession, nurses provide direct care to persons affected by and living with HIV, as well as serve as case managers and advocates. For example, the Association of Nurses in AIDS Care has a history of advocating for people affected by and living with HIV by collaborating with policy makers and community partners and by taking a stance against HIV-related stigma, health disparities, and the decriminalization of HIV (Association of Nurses in AIDS Care, 2020). Nurses in nonclinical roles assist patients in accessing health, food, and housing services and resources. In clinical roles, nurses and nurse practitioners provide high-quality direct patient care, education, adherence counseling (Dumitru et al., 2017; Rouleau et al., 2019; Tunnicliff et al., 2013), and in some situations, they serve as the medical director of ambulatory HIV clinics. Thus, nurses continue to play a pivotal role in HIV care.

The delivery characteristics of behavioral change interventions are central to their success and important with respect to feasibility, timeline, cost, and potential of the intervention to be broadly implemented (Gitlin & Czaja, 2015). Besides limited clarification of nurse interventionist characteristics, few of the studies addressed cost, and none of the studies compared delivery of the intervention by a nurse with another type of provider. These would be valuable considerations in nurse-delivered intervention trials in the future.


This review had limitations that must be considered when interpreting the results. Although the review conducted a thorough search of the literature using a team approach, relevant studies may have been unintentionally omitted. This review included only articles published in English, which may have omitted relevant nurse-led ART adherence interventions published in other languages. The review included only interventions that were nurse-led, in full or in part. Effective intervention strategies that have been led by other types of providers may exist that could be adopted for implementation by nurses in the clinical setting. Finally, the studies examined in this review were highly heterogeneous, especially concerning methods of calculating adherence.


Medication adherence continues to be a significant unmet challenge for optimizing patient outcomes (Stirratt et al., 2018). Despite effective and well-tolerated HIV medications, suboptimal adherence to ART treatment remains a major challenge for subgroups of the population living with HIV disease. There is a continuing need to deepen and strengthen the evidence base for adherence support interventions (Stirratt et al., 2018). To date, nurses have made important contributions to the science surrounding the enhancement of ART adherence. However, nurses have been underused and underrepresented in the science of HIV treatment adherence. Nurses comprise nearly half of the health care workforce and have been named the “most honest profession” for 18 years in a row by the Gallup Poll, yet only a small number of ART adherence trials that included nurses as interventionists were located for this review. Moreover, little information was provided in the published articles that explained why nurses were selected for delivery of the intervention or what unique qualifications the nurse brought that enhanced intervention effectiveness. This review has shown that nurse-delivered ART adherence interventions can be effective. However, more research is needed to better understand the important role that nurses can have in treatment adherence. Nurses are in a unique position to design and deliver multilevel interventions; more emphasis on this type of intervention design seems warranted. Finally, there is a need for more research to examine the comparative effectiveness and cost benefits of nurse-delivered interventions.


The authors report no real or perceived vested interests related to this article that could be construed as a conflict of interest. As with all JANAC feature manuscripts, this article was reviewed by two impartial reviewers in a double-blind review process. JANAC's Editor-in-Chief, Michael Relf, handled the review process for the paper, and Crystal Chapman Lambert had no access to the paper in her role as an editorial board member or reviewer.

Author Contributions

All authors participated in the conceptualization, design, data interpretation, writing, and final approval. C. Chapman Lambert, B. Galland, and N.R. Reynolds participated in the data collection. B. Galland and N.R. Reynolds summarized the data.

Key Considerations

  • Adherence to antiretroviral therapy is essential to achieve optimal HIV health outcomes, yet more than half of Americans living with HIV struggle to achieve viral suppression.
  • Several influential studies have examined strategies to enhance adherence to antiretroviral therapy and have demonstrated effectiveness. However, results are mixed, and interventions have primarily addressed individual-level factors.
  • Nurses play a pivotal role in the care of people living with HIV and often have the most contact with patients, allowing for rapport building.
  • Nurses are well-positioned to deliver and lead behavioral medication adherence interventions.
  • Additional rigorous studies are warranted to examine the effectiveness of nurse-delivered interventions to enhance adherence to HIV treatment in diverse settings.


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                adherence; antiretroviral therapy; HIV; review

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