“I Feel Like I Don’t Even Have HIV Anymore”—Facilitators,Barriers,and Experience regarding Use of Long-Acting Injectable Antiretroviral Therapy Among Persons with HIV in North Carolina

Abstract

As access to long-acting injectable antiretroviral therapy (LAI ART) expands, understanding patient perceptions and experiences around LAI should inform equitable scale-up and effective implementation strategies. This study used qualitative research design relying on semi-structured interviews conducted among persons with HIV (PWH) who were either virally suppressed on oral treatment (n = 11) or had received at least one dose of injectables (n = 7). Approximately half of participants identified as male (10/18) and most identified as African American (17/18). Among participants on oral ART, many described the prospect of injectable treatment as likely convenient and discreet, relieving the stress of remembering to take daily pill. Nearly all had heard of LAI ART prior to the interview, often from television or internet commercials. Most were excited about less frequent dosing, though expressed concern about the logistics involved in coming to clinic every two months. Many expressed uncertainties regarding the relative effectiveness of LAI ART compared with oral therapy and were wary of potential pain related to injections. In contrast, all persons on LAI ART described injection-site soreness as manageable. In addition to acknowledging the convenience of every-two-month injections, some persons receiving LAI ART expressed relief by lifting the emotional stress of taking a daily-pill that reminded them of their HIV positive status. Emerging clinical trial data supports the individual and public health benefits of LAI ART, regardless of prior viral-suppression; our work adds to a growing body of literature demonstrating the potential psychological benefits associated with this novel treatment modality for PWH regardless of recent viral-suppression.

Introduction

Monthly or every-two-month intramuscular injections of long-acting cabotegravir (an integrase strand-transfer inhibitor) and long-acting rilpivirine (a nonnucleoside reverse-transcriptase inhibitor) are safe,¹ and noninferior to daily oral antiretroviral therapy (ART) for maintaining HIV viral suppression.^2,3 The less frequent dosing of long-acting injectable (LAI) ART makes it a compelling alternative to daily oral ART, particularly for people with HIV (PWH) who may struggle with adherence to daily medications owing to diverse barriers related to access, stigma, and life routines.⁴ Increasing evidence is supporting use of LAI ART for PWH who struggle with daily oral pills. Findings from the ABOVE study (a real world retrospective cohort study in the United States) demonstrated that patients on LAI ART had higher treatment adherence (72% vs. 43%, p ≤ 0.001) and persistence (274 vs. 256 days, p < 0.001) compared to those on oral ART.⁵ Among the patients in the above study, most were male (73% in each cohort) and more than 40% were ≥50 years old (44% in the LAI ART cohort and 43% in the oral ART cohort). In 2022, Food and Drug Administration (FDA) removed the requirement for the one month daily oral lead removing a potential barrier for persons who have challenges with daily pills.⁶ The potential role of LAI ART as it relates to individual and population health has also been explored in modeling, with multiple studies suggsting that LAI ART has the potential to reduce HIV incidence by improving viral suppression.^7
–9 Emerging evidence from the Trio Cohort and OPERA cohort studies further suggests high virological suppression in viremic patients with LAI ART.^10,11 Interim trial data from the LATITUDE Phase III trial has found that LAI ART has superior efficacy as compared with the oral therapy for those who experience challenges with adherence.¹² Other observational projects have found LAI ART for PWH with viremia to be feasible with promising early outcomes for hard-to-reach patients such as those experiencing housing instability or homelessness.^13,14 Alongside the benefits of LAI ART for PWH with viremia, there may concurrently be benefits for those who are already suppressed on oral ART.

After approval by the FDA in January 2021, LAI ART programs have been started at several clinics in the United States, however implementation challenges persist.^15,16 One qualitative study of provider perspectives raises insurance-related challenges, insufficient resources, and lack of interprofessional coordination as obstacles to implementation.¹⁷ A survey of 40 Ryan White clinics in USA found that 20% were not at all ready to implement LAI ART while 52% were slightly or somewhat ready.¹⁸

Several articles with PWH and community stakeholders discuss potential challenges, acceptability, and preferences related to implementing LAI ART; however, the body of literature around LAI ART lacks perceptions and lived experiences of those for whom LAI ART was made available, or those using LAI ART outside of trial settings, in the early post-FDA approval period.^19

–22 This study aimed to assess knowledge, perceived barriers, perceived and experienced benefits, and key drivers to accepting LAI ART among PWH receiving care at a large academic medical center in the Southeastern United States.

Methods

Study settings

The University of North Carolina Infectious Disease (UNC ID) clinic is a safety net clinic that introduced LAI ART in January 2022. The UNC ID clinic serves a unique population drawn from across North Carolina (NC), typically engaging around 2,000 PWH annually from more than 80 (of 100) NC counties.

Participant recruitment and data collection

We used purposeful sampling to recruit PWH who were virally suppressed (<40 copies/mL) at their most recent measurement. We also engaged a subset of PWH who had initiated LAI ART. A research manager introduced the study in-person on the day of or via phone in advance of their scheduled provider visit and offered details about the study to interested participants. All participants were at least 18 years of age and completed an informed consent process. Participants were interviewed by study staff either in person or via HIPAA-compliant video conferencing (Zoom), depending on the participant’s preferences and availability.

Interviews were conducted between January 2022 and December 2022 and ranged between 30 and 40 minutes. We used a semi-structured interview guide to conduct the interview. Topics included participant experiences starting oral ART, switching medications, knowledge around LAI ART, as well as perceived or experienced barriers and facilitators related to LAI ART. All participants were given a $50 gift card for their participation.

All interviews were conducted in English and audio recorded. The recordings were transcribed verbatim by professional transcribers. We removed any personal identifiers from all transcripts to protect the confidentiality of participants.

Data analysis

We used directed content analysis to analyze interview transcripts. With a directed approach, analysis starts with relevant research findings as guidance for initial codes.²³ To develop the initial codebook, we drew from the interview guide and our initial review of the transcripts. Two independent coders piloted the codebook and compared results to iteratively adjust the codes and code definitions as needed. The two coders then coded all transcripts independently and met to compare coding and resolve any discrepancies through discussion. We used ATLAS.ti V.23 to complete the coding process. Code frequency reports from ATLAS.ti were exported, and overlapping themes were grouped together. Results were summarized per the study goals and based on salience of findings.

Ethics statement

The study was approved by the UNC Chapel Hill (IRB Number 21–2517).

Results

Participants demographics

Approximately half of participants identified as male (10/18), and most (17/18) identified as African American. Roughly one-third (7/18) of participants were taking LAI ART at the time of their interview (i.e., had received at least one injection). Those on LAI ART had a median age of 48 and those on oral ART had a median age of 49 (Table 1). In general, participants lived within a 1-hour drive to the clinic, though participants lived as far as 2 hours away.

Table 1.

Demographic Characteristics of Persons with HIV Who Participated in the Study

	LAI users (n = 7)	Oral ART users (n = 11)
Age (Median, range—minimum and maximum)	48 (33–58)	49 (25–68)
Distance from clinic (Number of minutes to drive to clinic)	30 (15–45)	45 (20–120)
Gender
Male	4	6
Female	3	5
Employment
Employed	3	5
Unemployed	4	6

LAI, long-acting injectable; ART, antiretroviral therapy.

PWH experience with oral ART (n = 18)

Most participants in our study have been living with HIV for more than a decade; some were diagnosed when highly effective oral medications for viral suppression were still being developed. Many reported switching ART regimens in the past. These participants commonly described an overall positive experience in switching to newer medications, which often consolidated multiple pills and lengthened dosing intervals. Participants reflected that such conversations of switching ART in the past were primarily initiated by their providers.

Although our sample was limited to PWH who were virally suppressed at their most recent assessment, many participants described initially struggling with adherence to daily oral ART. The reasons for these struggles varied from unpleasant treatment side effects to physical and social conditions (e.g., depression, unstable housing) to having a busy routine and general forgetfulness. Regardless of the reason, challenges with adherence were often described as a significant source of stress. Once patients had identified ways to integrate oral ART into their personal routine, most felt that adherence was no longer a problem as their treatment simply became a part of their everyday life.

LAI ART perceived barriers among non-LAI users (n = 11)

Drawing from these experiences and their current circumstances, participants who were not yet on LAI ART (n = 11) articulated concerns transitioning from their present regimen to injectable treatment. Several relayed the importance of control over their HIV treatment. For example, one participant shared that the physical act of taking a pill every day assures them that the medication is “working,” while another noted that switching to LAI ART required trusting someone else to administer it correctly.

One participant worried about their body “accepting” a new treatment, especially when they knew that the current oral treatment was working for them. Others were concerned about the effectiveness of the medication generally and its ability to keep them undetectable along with possible side effects:

With the injection, the bad thing—my concern would be whether my body would accept it. Because I already know now—the pills that I’m takin’ now, I’m good with it.

—LAI non-user (PT4)

Aversion to needles and the anticipated associated soreness was also a common concern, though some shared that they have been getting injections for other reasons and would be okay with receiving shots for HIV treatment.

For many participants, distance to clinic and the cost of transportation were salient logistical concerns as they would have to come to the clinic more frequently to receive injections. This was notably a concern for participants who lived further away from the clinic, were not employed, and/or were dependent on charity care to cover transportation:

Cause I don’t work, it wouldn’t change too much. Only thing would be gas. It would be the only burden that I would have to try to come up with. I don’t know, through the charity care that I have, whether they would do every two months. We get a certain budget.

—LAI non-user (PT7)

Visit frequency was less of a concern for participants who were visiting the medical center more often already for other comorbidities:

I come every six months [to the HIV clinic]. You figure when I would see my psychiatrist […] once a month, so that’s not a big deal with me.

—LAI non-user (PT1)

LAI ART perceived facilitators/benefits among non-LAI users (n = 11)

Participants also described perceived and experienced benefits with respect to LAI ART. Among those who were not on LAI ART, most were enticed by the prospect of not having the stress of remembering to take a pill every day and avoiding missed doses, connecting LAI ART with convenience. More specifically, participants describe a sense of relief, lifting the cognitive burden of the daily pill, especially during travel or other nonroutine circumstances.

Participants had mixed perspectives on the discreetness of LAI ART as compared to daily pills.

For example, while one participant felt that not having to maintain a pill box or carry pills made LAI ART more discreet, another participant noted that having multiple visits to the clinic may make cohabitants or other people around suspicious, making it less discreet.

Because I think it would help me out a lot because I forget my dosages. Then I have extra activities, and then I don’t want my medicine to be loose, or fallin’ out my pillbox, or not keeping up with my pillbox, or—you know? It’s discreet.

—LAI non-user (PT2)

Because some people are a little reluctant in having to be so—you would actually have to come all the time to get this medication, I mean, to come get the injection. I guess it would be, I would think, less discreet for them, maybe, I’m thinking. They can get a mail order medication come to their house. They can take a pill at home. Nobody has to know about it, family or anyone, if they don’t. They might say, “What goin’ on with you?” if they didn’t know, if they didn’t already know, if they had some reservations about tellin’ people. That would be the only reason.

—LAI non-user (PT1)

When we asked participants not on LAI ART whether they would switch away from their oral regimen, most said they would “choose” LAI ART, but all wanted more information regarding effectiveness of the newer therapy.

Experiences of using LAI ART (n = 8)

Participants who were already receiving LAI ART at the time of the study (n = 7) described an overall positive experience with the treatment. They appreciated the convenience offered by LAI ART and elimination of stress of taking a pill every day. One participant acknowledged the effectiveness of LAI ART and that it keeps them undetectable, just like pills:

Convenience and it’s covered by insurance, so not much out of pocket. It does the same job as well, which is the goal is to remain undetectable. It does that, so it’s effective.

—LAI user (PT16)

With respect to the injection itself, most participants confirmed it was indeed painful to take the shot, but that the pain was manageable and/or transient:

The pain that—the medicine that was gettin’ injected into you. I think that might’ve been what was hurtin’. The needle itself, I don’t know. I’m used to needles ’cause I’ve had needles stuck on me a long time. Oh, it was really fast. It wasn’t that long at all. As soon as it get in there, the pain is gone. Nothin’ really that long at all, probably a second or two. That’s not very long. Yeah. It hurt for a couple of seconds, like I said, but it wasn’t no—I didn’t have the problems with no swellin’ on there or redness or none of that, either.

—LAI user (PT13)

Some participants further shared how their previous regimen was a reminder of their diagnosis as they had to take a pill every day. For one participant, in the absence of daily pills, LAI-ART offered a sense of peace and stability:

It helps me by not forgetting doses and thinking about it every day. It makes me feel better. It makes me kind of forget that I have that. Not really, but it’s–I don’t have to be thinking about it every day. It’s a little less stressful. I’m very happy with everything, with the service. The doctors are very nice. I think they help me a lot with anything I need. My life is much better. I quit drinking ’cause I feel a little more better, more secure.

—LAI user (PT15)

Another participant even compared LAI ART to an HIV cure, stating that they felt that they did not have HIV anymore:

I feel like I don’t even have HIV anymore. I feel like I’m just cured and—I do. I feel like I don’t have anything. I’m just goin’ there just to get some shots. It don’t bother me. It don’t bother me at all. It beats takin’ a pill, swallowing a pill every day.

—LAI user (PT17)

These reflections highlighted not only the medical and logistical benefits of LAI ART but also illuminated the potential psychological benefits experienced by people actively receiving injectable treatment.

Discussion

PWH on oral ART voiced concerns regarding LAI ART effectiveness, the need for additional visits and associated commute costs, and potential unknown side effects including injection site pain or soreness; and even though this group was virally suppressed on oral ART, per study eligibility, there was often a desire to explore an option that would not require a daily pill. Patients on LAI ART primarily reported positive experiences, and generally found the soreness to be manageable. Our study highlights lived experiences of PWH using LAI ART outside of trial settings along with perspectives of non-LAI users, finding that the convenience of monthly or bimonthly injections with LAI ART was an appealing alternative to daily oral pills.

Our study findings supporting perceived convenience of LAI ART corroborate with other studies conducted in the United States and globally. A study in Houston, Texas collected perspectives of PWH who were not using LAI ART and found the elimination of daily pills was the most commonly perceived benefit (74%, n = 374). The same study also reported 43% being worried about the effectiveness of LAI ART, a theme that also emerged among our participants.²¹ A systematic review of barriers to LAI ART revealed the challenges of side effects, pain and soreness, and transportation, similar to our study.¹⁹ Perceived concerns around increased visits and costs were also reported by a commentary that focused on implementation of LAI ART in lower- and middle-income countries.²⁴

Notably, LAI ART’s need for an in-person visit every two months might be a salient barrier to use for many PWH. However, this could be overcome by delivering LAI ART outside of HIV clinics and at locations such as pharmacies or at home.²² An implementation science study that explored the possibility of storing the medication at home in refrigerators and delivering those injectables at home by health care professional found high satisfaction and no difference in sustained virological suppression.²³ Another implementation science trial found no differences with respect to efficacy, safety, or satisfaction among clients who chose to get LAI ART at clinic and those who chose to get it at home.²⁴ A survey that examined the perspectives of PWH in Southern Carolina around receipt of LAI ART at home revealed that at-home mechanism may also help with some enacted stigma.²⁵ While we found mixed perspectives on LAI ART’s discreteness, participants of an acceptability study in Vietnam were enthusiastic about the discreteness it offered.²⁶

Several participants who were receiving LAI ART felt as though this new treatment modality helped alleviate the negative psychological impacts of managing HIV with a daily pill. This theme also emerged in a mixed-method study in southern California that explored patient and physician preferences for long-acting modalities, which found that LAI ART had the potential to reduce reminders of their HIV status which was a perceived advantage.²⁶ Another acceptability study in Paris had similar findings with psychological benefits of a nondaily treatment since it would make patients not think about their status outside the medical appointments.²⁰ Further, perspectives of PWH in beyond study revealed that LAI ART was never or rarely an unwelcome reminder of their HIV status.²⁷ Because stigma and psychological conditions such as depression remain a key and persistent barrier to HIV treatment and prevention efforts, these impacts are notable and worth further exploration in future studies of LAI ART.

A strength of our study is our ability to assess perspectives about LAI ART among PWH on oral ART as well as those receiving LAI ART outside of a clinical trial context in the United States. However, we only included PWH on virologically suppressive oral ART given the potential confusion introduced by discussing a treatment alternative that, at the time of our study, would not generally be made available to PWH who were viremic. The perspectives of PWH who are viremic, particularly those who are struggling with adherence to daily oral ART, likely differ from the participants included in our study. Our study also contextualizes the use of LAI in settings where patients travel not just from the nearby areas but also from far off locations.

Long-acting forms of ART are promising HIV treatment modalities for PWH and offer a form of therapy that is generally perceived as convenient and acceptable. Insights from those receiving LAI ART indicate that this treatment may also provide psychological benefits, including stress relief and a sense of stability. However, LAI ART may present logistical challenges that may be unacceptable for some patients, and for some, removing the daily pill may be an undesirable shift in control and confidence in HIV management. Although the individual and public health benefits of expanding LAI ART use to PWH with viremia are suggested by models and supported by emerging clinical trial data, quantifying the full benefit of LAI ART should also consider these psychological benefits even for those durably suppressed on daily oral ART.

Footnotes

Acknowledgments

Foremost, the authors are thankful to our research participants who gave their valuable time and shared their life experiences with us. The authors are also thankful to the support of UNC Chapel Hill’s Gillings School of Global Public Health and UNC Infectious Disease Clinic for their consistent support. The authors would further like to express gratitude to B.J. Turner, Jonah Pierce, and Tia Morgan for their valuable effort to make this study possible.

Author Disclosure Statement

The authors declare no conflicts of interest.

Funding Statement

This study was supported by pilot funds provided by North Carolina Translational and Clinical Sciences Institute (UM1TR004406) and the University of North Carolina at Chapel Hill Center for AIDS Research (P30AI050410). SER received additional support from Doris Duke Charitable Foundation grant #2020143.

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