Multi-tablet, Single-Tablet, or Long-Acting Antiretroviral Treatment for HIV: A Cross-sectional Study of Patient Preferences in the United States and Spain : Journal of the Association of Nurses in AIDS Care

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Research Brief

Multi-tablet, Single-Tablet, or Long-Acting Antiretroviral Treatment for HIV: A Cross-sectional Study of Patient Preferences in the United States and Spain

Carracedo, Alfredo Soler RN, MSc, MSN*; Oliveira, Vitor PhD; Saz, Jorge; Pujol, Ferran; Milinkovic, Ana MD, PhD, MSc; Webel, Allison RN, PhD, FAAN

Author Information
Journal of the Association of Nurses in AIDS Care: November/December 2022 - Volume 33 - Issue 6 - p 638-645
doi: 10.1097/JNC.0000000000000343
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Major breakthroughs in HIV treatment over the past decades have rendered HIV a chronic manageable condition, allowing many individuals to live longer, healthier lives (Singh et al., 2019). However, this is only possible if people with HIV (PWH) adhere to the antiretroviral therapy (ART; Chen et al., 2017). Factors associated with poor ART adherence include pill burden, medication side effects, health beliefs, busy schedules, substance abuse, and other comorbidities (Cheng et al., 2018).

Currently, oral ART formulations are routinely available to PWH, whereas injectable long-acting ART (ILART) formulations administered intramuscularly (IMs) every 4 or 8 weeks, such as cabotegravir, an integrase inhibitor (II), and rilpivirine, a non-nucleoside reverse transcriptase inhibitor, have been recently approved (Singh et al., 2019). The use of these long-acting agents could potentially offer better adherence, leading to improved health outcomes for PWH (Simoni et al., 2019). PWH would only need to receive an IM injection in a health care setting once every four or eight weeks, instead of taking ART tablets every day (Singh et al., 2019).

Understanding factors that affect ART adherence is paramount for the successful management of HIV infection (British HIV Association, 2016). As ILART is not routinely prescribed to treat HIV, there is limited scientific literature regarding PWH's acceptability of this new form of ART treatment, and therefore, there is a need for data to better understand PWH's preference for ILART (British HIV Association, 2016; Department of Health and Human Services, 2021). The objectives of this study were to (a) understand factors that affect adherence and (b) explore the acceptability and preference of frequency and route of administration of ART, comparing these findings in two distinct settings.


Study Design

All participants completed an anonymous, cross-sectional survey. It was conducted at two outpatient settings including the John T Carey Special Immunology Unit at Case Western Reserve University in Cleveland, USA, and at Barcelona Checkpoint, Spain, between November 2020 and February 2021.


The survey was developed by reviewing the extant literature and included questions commonly used to investigate demographics, adherence, HIV-related items, and ART preference. After the team discussion and expert review, the final survey was developed and consisted of 15 total items.

Demographic-related questions asked participants to self-report from various options regarding their gender, sexual orientation, age group, race, and educational level.

To assess ART adherence, participants were asked if they had forgotten to take their ART in the last week and the last month. To ascertain their HIV characteristics, participants self-reported the year of HIV diagnosis, if they had an undetectable viral load, current CD4+ T-cell count, the name of the ART they were taking, and if they were happy with that ART.

For year of HIV diagnosis, the research team decided to group all the answers into three categories: 1985 to 1996, 1997 to 2009, and 2009 to 2020. These categories were created to facilitate the statistical analysis, particularly findings associated with years to ART preference, because we lacked power to establish those relationships with individually reported years.

Participants also reported which form of HIV treatment they preferred out of five possible options. Oral ART consisting of: (a) any number of tablets multiple times a day, (b) any number of tablets once a day, or (c) one tablet once a day. The other two were ILART: (d) one IM injection at the clinic once a month, or (e) one IM injection at the clinic once every 2 months. Participants also reported if they had previously received an IM injection.

The survey given in the United States and Spain contained the same items, except for the educational level of participants, because the education system in both countries differs substantially, so different response options were provided. Clear and unambiguous language, in both English and Spanish, was used. In Spain, all questions were answered by self-report. In the United States, participants answered the questions by self-report, except latest CD4+ T-cell count and being undetectable or not, because the research team already extracted that information from the medical record. The survey took 5 to 15 min to complete. Participants could skip any questions they did not want to answer. There was no financial compensation or any other incentive for participants taking part in the study.

Sample and Setting

In the United States, individuals participating in the PROSPER study (Webel, Long, et al., 2020) were invited to participate. The PROSPER study is exploring which specific aspects of physical activity and dietary intake affect the symptom experience in PWH. In Spain, participants were recruited through one of the largest sexual health clinics—Barcelona Checkpoint—which sees around 8,000 individuals annually. Around 1,100 PWH at Barcelona Checkpoint agreed to be emailed about research, and they were selected as recruitment targets.

Eligiblity criteria

Adults (≥18 years of age), diagnosed with HIV, receiving care at one of the aformentioned clinics, taking ART medication, who could understand either English or Spanish language, depending on the location, were eligible to participate in the study.

Ethical Considerations

Ethics approval at King's College London was sought and obtained for the conduct of this study in Spain, as part of a Master's degree in nursing award, IRB number LRU-19/20-20,609. Ethics approval at Case Western Reserve University was sought and obtained for the conduct of this study in the United States, IRB number STUDY20180761, as an amendment to the PROSPER study.

Data Collection

In the United States, in-person appointments at the John T. Carey Immunology Unit were restricted due to the coronavirus disease-19 (COVID-19); however, participants of the PROSPER study (Webel, Long, et al., 2020) were able to attend in-person research visits, thereby completing the survey in person. In Spain, data were collected via an active clinic-based registry of individuals interested in research participation because in-person appointments were restricted due to COVID-19.

In the United States, participants in the PROSPER study (Webel, Long, et al., 2020) who attended their routine PROSPER research visits were introduced to the study by a member of the research team, who detailed why the study was being conducted, what it involved, and the benefits, potential risks, and how to withdraw. Those electing to participate provided written, informed consent. Participants completed a paper version of the survey, and the fully de-identified answers were uploaded on a Microsoft Forms survey that contained the exact same items by a member of the research team.

In Barcelona, an email was sent to 1,100 PWH who indicated their interest in participating in HIV-related research. The email contained a link inviting them to complete the anonymous survey, made with Microsoft Forms, and a brief description of the study, explaining the details of the study, what it involved, the benefits, potential risks, and how to withdraw. The survey and all the information in the email were in Spanish. To ensure participants read the document before completing the survey, the first question of the survey, which contains a box that participants had to tick, read, “please tick this box if you have read the participant information sheet and you choose to participate.” Return of survey was considered consent.

Statistical Analysis

Descriptive statistics are presented as frequencies and valid percentages, to account for missing data. Chi-square tests were used to check for statistically significant differences in the contingency tables, combined with both univariate and multivariate analyses to examine associations with ART preference. To detect a medium effect size with 14 independent variables, a sample size of 135 participants was required to achieve 80% power at alpha 0.05 for a two-tailed F test. A significant association was established if p < .05. Multivariate testing was used to assess the association between year of HIV diagnosis, happiness with current ART, and having ever received an IM injection with preference for an ILART. Those variables were chosen as univariate analysis showed p ≤ .2. Analyses were conducted by using SPSS 27.0 (SPSS Inc., Chicago, IL).


Participant Characteristics

In the United States, 55 participants completed the survey (Table 1), and of those, most participants were identified as male (83.6%), homosexual (50.9%), Black/African American (66.7%), and had less than a Bachelor's degree (67.9%). On average, participants were diagnosed with HIV between 1985 and 1996 (45.5%), had an undetectable HIV viral load (89.1%), were currently taking a single-tablet ART regimen (60%), had taken all their ART in the last week (77.8%) or the last month (68.6%), and were happy with their current ART (98.2%). Approximately 56% reported never receiving an IM injection.

Table 1. - Participant's Characteristics
Variable Total (N = 196), n (%) United States (N = 55), n (%) Spain (N =141), n (%) p
Sex <.01
 Male 181 (92.8) 46 (83.6) 135 (96.4)
 Female 14 (7.2) 9 (16.4) 5 (3.6)
Sexual orientation <.01
 Homosexual 150 (78.5) 27 (50.9) 123 (89.1)
 Heterosexual or bisexual 41 (21.5) 26 (49.1) 15 (10.9)
Age group <.01
 18–34 years 39 (19.9) 5 (9.1) 34 (24.1)
 35–54 years 101 (51.5) 18 (32.7) 83 (58.9)
 ≥55 years 56 (28.6) 32 (58.2) 24 (17)
Race/ethnicity <.01
 Black/African American 38 (19.5) 36 (65.5) 2 (1.4)
 White 119 (60.7) 16 (29.1) 103 (73)
 Latino 34 (16.8) 1 (1.8) 33 (23.4)
 Other 5 (3) 2 (3.6) 3 (2.1)
Educational level <.01
 Less than Bachelors 83 (43) 36 (67.9) 47 (33.6)
 Bachelors or more 110 (57) 17 (32.1) 93 (66.4)
Year of HIV diagnosis < .01
 1985–1996 39 (20) 25 (45.5) 14 (10)
 1997–2009 33 (16.9) 17 (30.9) 16 (11.4)
 2009–2020 123 (63.1) 13 (23.6) 110 (78.6)
Viral load .02
 Undetectable 185 (94.9) 49 (89.1) 136 (97.11)
CD4+ T-cell count .07
 ≤400 cells/mm3 13 (9.8) 9 (16.4) 4 (5.2)
 401–600 cells/mm3 45 (34.1) 19 (34.5) 26 (33.8)
 601–800 cells/mm3 33 (25) 9 (16.4) 24 (31.2)
 ≥801 cells/mm3 41 (31.1) 18 (32.7) 23 (29.9)
Current ART < .01
 1 tablet 128 (73.1) 33 (60) 95 (79.2)
 >1 tablet 47 (26.9) 22 (40) 25 (20.8)
Forgot to take ART in the last week .02
 None 166 (86.9) 42 (77.8) 124 (90.5)
 Once, twice, or three times 25 (13.1) 12 (22.2) 13 (9.5)
Forgot to take ART in the last month .69
 None 131 (69.7) 35 (68.6) 96 (70.1)
 Once 30 (16) 7 (13.7) 23 (16.8)
 Twice or more 27 (14.4) 9 (17.6) 18 (13.1)
Happy with current ART < .01
 Yes 168 (87) 54 (100) 114 (82)
 No 25 (13) 0 25 (18)
Ever received an IM .06
 Yes 107 (55.2) 24 (44.4) 83 (59.3)
 No 87 (44.8) 30 (55.6) 57 (40.7)
Note. Results expressed in frequencies (valid percentages) so as to account for missing answers.
Note. ART = antiretroviral therapy; IM = intramuscular.

In Spain, 141 participants out of 1,100 eligible candidates completed the survey, resulting in a 12.8% participation rate (Table 1). The majority of participants were male (96.4%), homosexual (89.1%), 35 to 54 years of age (58.9%), and White (73%), with a Bachelor's degree or more (66.4%). In regard to the HIV characteristics, most participants had been diagnosed between 2009 and 2020 (78.6%), had an undetectable HIV viral load (97.1%), were on a single-tablet ART regimen (79.2%), had not forgotten to take their ART in the last week (90.5%) or the last month (70.1%), and were happy with their current ART (82%). Twenty-one participants were unable to remember the name of their ART and 40.7% of participants had never received an IM injection.

Adherence to Antiretroviral Therapy Preference

Among participants in United States, the most preferred ART option was a single tablet, once a day (44.4%; Table 2). The least preferred ART options included any number of tablets multiples times a day, and one IM injection, at the clinic, once a month (5.6%). When comparing oral ART with injectable ART, 68.5% of participants preferred oral ART compared with those preferring IM ART (31.5%).

Table 2. - ART Preference
ART Total (N = 196), n (%) United States (N = 55), n (%) Spain (N =141), n (%)
Ways of disposal
 Any number of tablets, multiple times a day 3 (1.6) 3 (5.6) 0
 Any number of tablets, once a day 16 (8.3) 10 (18.5) 6 (4.3)
 One tablet, once a day 64 (33.2) 24 (44.4) 40 (28.8)
 One IM, at the clinic, once a month 10 (5.2) 3 (5.6) 7 (5)
 Once IM, at the clinic, once every 2 months 100 (51.8) 14 (25.9) 86 (61.9)
Combined forms
 Oral 83 (43) 37 (68.5) 46 (33.1)
 IM 110 (57) 17 (31.5) 93 (66.9)
Note. Results expressed in frequencies and valid percentages so as to account for missing answers.
Note. ART = antiretroviral therapy; IM = intramuscular.

In Spain, the majority of participants preferred one IM injection once every 2 months, at the clinic, over the other options (61.9%; Table 2). Any number of tablets, once a day, was the least preferred option (4.3%). Comparing oral ART with injectable ART, IM ART was preferred by 66.9% of participants compared with those preferring oral ART (33.1%).

Correlates of Preferred Form of Adherence to Antiretroviral Therapy Treatment

In the United States, having previously received an IM injection was associated with a preference for IM ART (odds ratio [OR] 11.18 in the multivariate analysis, 95% CI = 2.01-62.14, p < .01). In Spain, none of the variables correlated with ART preference when multivariate analysis were performed (ps > .05).

When participants from both sites were combined, three variables were associated with a preference for IM ART (p < .05) in the multivariate analysis: recent year of HIV diagnosis, not being happy with the current ART regimen, and having ever received an IM injection (Table 3). Participants who were diagnosed with HIV from 2009 to 2020 were 4.21-fold (95% CI 1.87-9.46, p < .1) more likely to prefer IM ART compared with those diagnosed with HIV before 2009. Those unhappy with their current ART regimen were 3.88-fold (95% CI 1.29-11.69, p = .02) more willing to take IM ART compared with those who were happy with their current regimen. Having previously received an IM injection was associated with 2.41-fold preference for IM ART (95% CI 1.29-4.51, p < .01).

Table 3. - Variables Associated With a Preference for Intramuscular Antiretroviral Therapy
Variable Univariate, OR (95% CI) p Multivariate, OR (95% CI) p
Year of HIV diagnosis
 1985 to 1996 Reference < .01 Reference < .01
 1997 to 2008 2.00 (0.77–5.23) 2.13 (0.78–5.85)
 2009 to 2020 3.90 (1.82–8.39) 4.21 (1.87–9.46)
Happy with current ART
 Yes Reference .01 Reference .02
 No 3.42 (1.22–9.54) 3.88 (1.29–11.69)
Ever received an IM
 No Reference < .01 Reference < .01
 Yes 2.24 (1.25–4.01) 2.41 (1.29–4.51)
Note. OR = odds ratio; CI = confidence interval; ART = antiretroviral therapy; IM = intramuscular.


Our study provides much needed, patient-centered data to the scant literature on this novel ART formulation. Results demonstrate an overall preference of ILART over oral ART when combining results from both sites (57% preferring ILART). Acceptability was higher in Spain (66.9%), with receiving an IM administration of ART every two months in the clinic being the most preferred option (61.9%). In the United States, 68.5% of participants prefer an oral ART, with one tablet once a day the most preferred option (44.4%).

The body of literature is inconsistent and reveals both high and low acceptance rates for ILART over oral ART. Kerrigan et al. (2020) reported 90% of participants preferring ILART over oral ART, Akinwunmi et al. (2021) reported 65.8%, and Rusconi et al. (2017) reported 83%. Dandachi et al. (2020) reported 61% of participants were likely or very likely to use long-acting ART, among them, 40% preferred injections, 41% pills, 18% an implant, and 1% an intravenous formulation. Carillon et al. (2020) conducted a qualitative study with PWH and PrEP users, showing no clear-cut pattern in favour or against ILART, highlighting the complexity of this choice. In clinical trials, such as FLAIR, LATTE-2, and ATLAS, participants who were given ILART reported acceptability levels of more than 80% (Orkin et al., 2020; Rizzardini et al., 2020).

The preference for oral ART may be explained by a variety of reasons, including comorbidities requiring additional oral daily medications, reduced cost, and fear of injection pain, among others (Simoni et al., 2019). The presence of other comorbidities that require oral medication could mean that participants do not consider the addition of an oral ART to their routinely prescribed medication to be a burden because one extra tablet would not represent a substantial increase in pill burden (Dube et al., 2020). Although ART is given free of charge in Spain, this is not always the case in the United States, where cost of the medication is an important variable for PWH to consider (Kerrigan et al., 2018; Simoni et al., 2019). Some of the participants who chose oral ART were perhaps concerned because ILART is a new form of medication, meaning that it could be expensive (Simoni et al., 2019). Kerrigan et al. (2018) asked PWH how much they would be willing to pay for ILART, and participants reported $184 per month, although this number should be interpreted with caution because the sample consisted of 11 participants and their financial well-being was not assessed, and therefore may not be representative of the PWH general population. Future research should specifically explore the relationship between perceived cost and acceptability of novel HIV treatment options. Extra visits to the clinic, as ILART must be given at the clinic either every four or eight weeks, could also represent an increase in cost and time (Webel, Schexnayder, et al., 2020). Trypanophobia, a fear of injections or needles, could also explain the reticence to ILART (Simoni et al., 2019).

Reasons for preferring ILART may include a desire not to take oral medication so as not be reminded about living with HIV, better adherence, lower pill burden, avoiding food considerations, stigma, and medical needs such as malabsorption, among others (Akinwunmi et al., 2021; Kerrigan et al., 2018). Regimen simplification has been shown to improve adherence and quality of life for PWH (Chen et al., 2017). ILART would decrease pill burden, resulting in a more simplified regimen, which could offer better adherence (Chen et al., 2017).

The preference for ILART observed among participants in the United States that had previously received an IM (OR = 11.18, 95% CI 2.01–62.1, p < .01) may be related to a previous positive experience receiving an IM injection, thereby increasing their willingness to undergo this procedure as part of their routine HIV care. It is important to highlight that long-acting cabotegravir and rilpivirine are administered as two gluteal IM injections, and participants were not asked about the nature of the IM injections they had experienced (Singh et al., 2019).

For all participants, those who were not happy with their current ART were more likely to try ILART (OR = 3.88, 95% CI 1.29–11.69, p < .02). Participants who were diagnosed between 2009 and 2020 were more likely to select ILART as a preferable option (OR = 4.21, 95% CI 1.87–9.46, p < .01). This may be explained by participants diagnosed with HIV in earlier years preferring to continue with ART that they are familiar with, know what to expect, and how to remain undetectable. Among younger participants, a higher prevalence of them were more interested in ILART, although our study may not be powered enough to observe a difference in this variable in the multivariate analysis.

As ILART is slowly being implemented as part of the routine care of PWH, health care professionals will have the opportunity to discuss this new form of treatment with eligible individuals. Registered nurses will play a central role in discussing, prescribing, and administering ILART. Health care settings will have to evolve to better accommodate the logistics of administering ILART (Akinwunmi et al., 2021). Ongoing and planned studies are exploring the implementation of ILART in different practice settings (Orkin et al., 2020).

Study Limitations

Limitations of our study include: participants were not asked about comorbidities, a cross-sectional design, the lack of a qualitative component, a nondiverse sample, and a low participation rate in Spain. Participants were not asked about the presence of other comorbidities that required medication to be taken, so the pill burden could not be studied. Cross-sectional studies are prone to nonresponse and recall bias, and in this study, one of the main nonresponse biases is that individuals in both Spain and the United States were interested in participating in research, which could mean individuals might be more likely to consider a novel approach on ART than those who are not willing to participate in research (Wang & Cheng, 2020). By combining qualitative techniques, such as focus groups, a more in-depth analysis could be performed and more exact reasons for the preference of oral versus IM ART could be obtained. When combining results from both sites, the majority of our participants were male, homosexual, and White. A more diverse sample, including individuals from different sex, race, sexual orientation, ages, year of HIV diagnosis, and those who had not previously expressed willingness to take part in research, to name a few, is needed to reflect the views of a more representative population. Generalizations to these groups cannot necessarily be made from our findings. Unfortunately, the researchers did not have access to the particular characteristics of the demographics of the population studied at both sites.


Our study found high levels of acceptance of IM ILART among PWH in Barcelona, but not in Cleveland. Being recently diagnosed with HIV, not being happy with their current ART, and having previously received an IM injection were associated with a preference for ILART over oral ART. Choosing between an oral or long-acting ART is a complex decision, with many factors that must be carefully taken into consideration. The implementation of ILART in health care settings presents logistical challenges, and registered nurses will play a key role in helping to redesign HIV clinics to facilitate the delivery of this form of ART. Further research, preferably using mixed methodology, is needed.


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. Allison Webel, JANAC's Deputy Editor, had no access to the paper in her role as an editor or reviewer and did not serve as the corresponding author.


This work was funded, in part, by the National Institutes of Health (NR018391, PI: A.R. Webel). The content is solely the responsibility of the authors and does not necessarily represent official views of the National Institutes of Health.

Author Contributions

All authors reviewed and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Individual specific contributions were: Conceptualization: A. S. Carracedo, J. Saz, F. Pujol, A. Milinkovic, A. Webel; Methodology: A. S. Carracedo; Formal Analysis: V. Oliveira, Investigation: V. Oliveira, J. Saz, F. Pujol; Resources: A. S. Carracedo, A. Webel; Data Curation: A. S. Carracedo, V. Oliveira; Writing—Original Draft: A. S. Carracedo, V. Oliveira; Writing—Review & Editing: A. S. Carracedo, V. Oliveira, J. Saz, F. Pujol, A. Milinkovic, A. Webel; Supervision: A. Webel, A. Milinkovic; Project Administration: A. S. Carracedo; Funding Acquisition: A. Webel.

Key Considerations

  • Overall, an IM ILART was the preferred option, although there are substantial variations between settings.
  • Choosing between an oral and injectable ART is a complex decision, with many factors to take into consideration. Further research combining qualitative techniques, such as focus groups, could provide a more in-depth analysis.
  • Registered nurses will play a key role in the discussion, prescription, and administration of ILART.


The authors thank all participants for taking part in this study. The authors also thank the research assistants—Robin, Vinh, and Martell—at the John Carey Special Immunology Unit in Cleveland, Ohio, USA, for their help with the running of the study. At Chelsea and Westminster Hospital, UK, the authors thank Suji for her help with statistics.


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Adherence; Antiretroviral; Cross-sectional study; Injectable; Long-acting; People with HIV

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