Treatment experience of people living with HIV who transitioned from oral to long-acting injectable antiretrovirals in Puerto Rico: A qualitative study.

Antiretroviral therapy (ART) has revolutionized the management of HIV, transforming it from a fatal disease into a chronic condition. By 2022, an estimated 39 million individuals worldwide were living with HIV [ 1 ]. Over 16,000 people are living with HIV in Puerto Rico in 2022, yet new cases have decreased over 45% from 2013 to 2022 [ 2 ]. This decline in new infections can be attributed, in part, to the significant advancements in ART and its broader accessibility. ART has played a crucial role in reducing the viral load in people living with HIV, making them less likely to transmit the virus to others [ 3 ]. Daily oral ART adherence is a critical aspect of managing HIV, yet it is often hindered by various barriers. Stigma and discrimination surrounding HIV status remain significant obstacles to adherence [ 4 ]. Individuals living with HIV may fear disclosing their status, leading to social isolation and reluctance to take their medication consistently. In addition, complex pill burden regimens and the potential for medication side effects can deter adherence [ 5 ]. The inconvenience and adverse effects of daily oral ART may discourage individuals from maintaining their treatment, which is essential for achieving viral suppression and reducing the risk of transmission [ 6 ]. In 2017, Puerto Rico was ranked 6 th in the prevalence of adults and adolescents living with HIV among the United States and its territories. Based on surveillance data from 2014, about 68% of people living with HIV on the island were in HIV care, but only 55% were virally suppressed and about 9% were undiagnosed [ 7 ]. Currently, collaborative agreements exist between the public and private sector as well as non-profit entities for the prevention and treatment of HIV. The Puerto Rico Ryan White Part B and AIDS Drugs Assistance Program Providers Network consists of 55 centers distributed throughout eight health regions [ 8 ]. Access to medications exists for patients without health insurance or with limited coverage through these programs. Main risk factors for HIV infection in Puerto Rico include intravenous drug abuse, high risk heterosexual sex, and men who have sex with men [ 7 ]. The greatest prevalence is in the metropolitan area of San Juan. Limitations in HIV care in Puerto Rico include stigma, barriers for prevention, inadequate education, and social determinants including housing instability and transportation [ 9 ]. The transition from oral ART to long-acting injectable therapy with Cabotegravir/Rilpivirine (LAI-CAB/RPV) represents a promising approach to addressing these challenges associated with adherence to oral ART. This approach involves the use of long-acting injectable formulations of Cabotegravir and Rilpivirine, which can maintain exposure at plasma concentrations exceeding in vitro 90% inhibitory concentrations with monthly intramuscular injections [ 10 ]. To this day, clinical trials have demonstrated that long-acting ART is non-inferior to daily oral ART, showing rates of viral suppression, treatment failure, and drug resistance similar to daily oral ART [ 11 ]. In the LATTE-2 trial, the percentage of participants with HIV-1 RNA suppression through 96 weeks was similar among those who switched to LAI-CAB/RPV and those who continued oral cabotegravir-based therapy [ 12 ]. Additionally, as part of these clinical protocols, some studies have quantitatively measured patient self-reported outcomes, such as satisfaction and quality of life, in patients who have transitioned to injectable therapy. In phase 3 ATLAS and FLAIR studies, the investigators utilized patient-reported outcome instruments to measure treatment satisfaction (HIVTSQ) and acceptance (ACCEPT general domain), health status (SF-12), injection tolerability/acceptance (PIN), and treatment preference. In pooled analyses, LAI-CAB/RPV-treated patients demonstrated greater mean improvements from baseline than the oral ART group in treatment satisfaction and acceptance. In both studies, ≥ 97% of long-acting group participants with recorded data preferred LAI-CAB/RPV treatment compared with prior oral therapy [ 13 ]. These results further support the potential of a long-acting injectable option for people living with HIV to improve adherence and quality of life. However, it’s important to acknowledge the limitations of quantitative research in capturing the nuanced and multifaceted aspects of patient experiences during this transition. This underscores the need for further qualitative investigations to explore patient perspectives, shedding light on the unique challenges, motivations, and coping strategies individuals employ during this process. This deeper understanding can enhance patient-centered care, provide insights into strategies for improving adherence and treatment outcomes, facilitate discussions with healthcare providers, inform future treatment recommendations, and encourage further research aimed at optimizing long-acting therapies, improving patient outcomes, and developing more patient-friendly treatment options. A qualitative study was conducted among people living with HIV participating in a Phase II trial of cabotegravir/rilpivirine (LATTE-2) in the United States and Spain [ 14 ]. The study explored participant experiences with LAI-CAB/RPV versus daily oral ART. Participants described the convenience of long-acting injections versus daily pills and emotional benefits such as minimized potential for HIV disclosure and eliminating the daily reminder of living with HIV [ 14 ]. The study yielded important results, highlighting that participants perceived LAI-CAB/RPV as a highly acceptable and desirable treatment option. This perception stemmed from the convenience of a monthly or bimonthly injection compared to daily pills, as the injectable achieved the benefit of eliminating the daily reminder of living with HIV. Importantly, these positive perceptions were consistent across diverse participant demographics, suggesting that long-acting ART holds promise for a wide range of individuals. This aligns with prior findings on the positive impact of reducing the number of daily pills on adherence and quality of life in HIV-positive patients, underscoring the potential long-term benefits of long-acting ART [ 14 , 15 ]. Nevertheless, the study identified several limitations, including its cross-sectional nature and the sample’s selectivity from a clinical trial, which may have influenced the positive experiences reported by participants. Hence, we aim to comprehensively investigate the treatment experience of individuals living with HIV who have transitioned from conventional oral antiretroviral therapy to long-acting antiretroviral therapy using Cabotegravir/Rilpivirine in Puerto Rico. By exploring the personal narratives of participants, we seek to gain a deeper understanding of their journey, challenges, and successes in adapting to this novel treatment approach.

The study included 10 participants living with HIV who transitioned from oral ART to LAI-CAB/RPV. Participants’ mean age was 67 years (SD = 9), ranging from 46 to 81 years (see Table 1 ). Seventy percent of the study participants were men, and 30% were women. Most of them identify themselves as heterosexual (60%) and 40% as homosexual. On average, study participants have taken oral ART medication for 23.2 years (SD = 8.7), ranging from 10 to over 30 years. Study participants have been on LAI-CAB/RPV for at least 6–24 months. All participants had a viral load of ≤ 50 cp/mL, with CD4 counts within the normal range, which were maintained both before and after the transition to the injectable therapy. Common comorbidities included hyperlipidemia (70%), hypertension (60%), hypothyroidism (40%), and diabetes mellitus type 2 (30%). * DM-2, diabetes mellitus-2; GERD, gastroesophageal reflux disease; COPD, chronic obstructive pulmonary disease; ESRD, end-stage renal disease; CKD, chronic kidney disease; CD4, cluster of differentiation 4. For most of our study participants, receiving an HIV diagnosis was a life-changing event, as Angélica, a 46-year-old female, shared, “It felt like the ground disappeared beneath my feet. I thought my life was over.” In addition to having to manage the implications of their new HIV diagnosis, they learned that they needed to take ART medication for the rest of their lives. They later understood that their ART was essential for their lives but did come with challenges and struggles. In this section, you will get to know our participants’ lived experiences with their oral regimen. Participants’ experiences with oral ART were marked by several challenges, including the complexity of regimens, adverse effects, and social implications. Many started with regimens involving multiple medications taken several times a day. Dennis, a 65-year-old male, recalled “Back when I started... with oral medication, cocktails still existed. It was a cocktail of 10 to 15 pills morning, noon, and night. So how was I supposed to socialize publicly at work and all that having to gulp down those cocktails’ morning, noon, and night?” Adverse effects ranged from gastrointestinal discomfort to psychological distress. Reiki, a 68-year-old male, recounted, “ There was one now I can’t remember the name that raised my liver enzymes a lot. They had to suspend the treatment. They raised them almost to a thousand”. Lipodystrophy had a profound psychological impact. July, a 64-year-old male, noted, “...and I’ll always remember that when the side effects started like lipodystrophy that really affected me emotionally”. Adherence challenges were prominent, including the burden of daily medication, difficulties swallowing large pills, and disruptions to daily life. Ernesto, a 61-year-old male, emphasized the necessity of adherence, saying, “ For me, my life depends on those bottles. If I don’t take them, I will die”. Participants often had to hide their medications to avoid stigma and maintain privacy. Laura mentioned, “I used to hide my pills in the fridge so that my family wouldn’t find out”. The social implications of oral ART were significant. The need to take multiple doses throughout the day often disrupt social activities, travel plans, and work commitments, leading to feelings of isolation and frustration. For instance, Reiki shared, “...at that moment it made me nervous passing through customs or airport security seeing a young person with so many pill bottles because the medications were three huge bottles. Plus, with that concern of having to carry enough supply of the medications for every day, it creates tension”. Our study participants considered the transition to LAI-CAB/RPV a transformative experience that impacted their lives from many standpoints. All of them considered LAI-CAB/RPV something positive that improved their lives personally and socially and helped them have a sense of ‘normalcy’. Study participants learned about LAI-CAB/RPV through different sources, such as leaflets, at the pharmacy, and through a talk by the clinic’s director. The idea of a new long-acting injectable treatment for HIV was well received by the study participants. As Laura shared: [referring to LAI-CAB/RPV] “I already knew it was in the making; I have been waiting for 15 years and said yes. I use it every month; I don’t care. If you prick me, I don’t care. And she [referring to the clinic staff] asks me, are you sure? And I said, yes, I am”. Most of the study participants were invited to transition to the LAI by the healthcare provider at Centro Ararat and access to the injectable therapy was facilitated by them who efficiently managed the paperwork and approval process. Ernesto highlighted the ease of accessing injectable therapy: “Yes, that was a blessing... when the doctor approached me, I said yes, let’s see if the medical plan approves it, and thanks to the Lord, I haven’t had any kind of situation”. However, some faced delays with pharmacy services, requiring proactive follow-up to ensure timely delivery, as mentioned by July: “ I mean the bureaucratic process of medical plans and the specialized pharmacy that is dedicated to distributing the medication... I have to keep pushing, as one says, the specialized pharmacy to ensure it arrives on time because it is very important for me, and I told them so... I mean, every two months I have to stay on top of it, and it creates tension for me”. The first-dose experience elicited mixed emotions of excitement and anxiety. Ernesto described his anticipation as a “gift of life,” while also noting initial concerns about potential side effects and reactions. Laura expressed a similar sentiment, feeling both nervous and hopeful about the new treatment. Ismael recounted his positive feelings, stating, “ I felt happy because it’s a success. It’s every two months that I don’t have to worry about pills anymore”. Most participants reported mild discomfort at the injection site, which subsided within a day. Some experienced mild symptoms such as body aches or chills, manageable with over-the-counter medication. Angélica, reflecting on her experience, stated: “I do feel a little sore in the area if I touch it and such, but it wasn’t something like I couldn’t walk. But I didn’t mind as long as I don’t have to take a pill anymore, I’m happy”. Participants demonstrated a high level of acceptance and adaptability to potential adverse effects, emphasizing their willingness to tolerate discomfort in exchange for the benefits of injectable therapy. Participants showed a remarkable level of resilience and adaptability to the new regimen. Ismael noted, “I didn’t have any reactions to the medication. I felt good, thank God .” Laura highlighted the improvement in her quality of life, stating, “The first injection was a bit nerve-wracking, but after that, everything improved so much. I told my doctor he saved my life”. Participants demonstrated high adherence to LAI-CAB/RPV, appreciating the reduced frequency of clinic visits and the flexibility it afforded. Laura mentioned, “Before, I had to come monthly for medication refills. Now, I only come every two months, which is much more convenient”. Participants also noted the ease of incorporating the bi-monthly clinic visits into their routines without the daily reminder of their condition, as was the case with oral ART. The transition to LAI-CAB/RPV brought significant emotional relief and a sense of normalcy. Participants emphasized freedom from the constant reminder of their condition that daily pills represented. Angélica described it as, “Freedom. It means freedom. I don’t have to think, did I take it, did I not take it, where is the alarm? It’s like normalizing my life”. Laura echoed this sentiment, stating that the injectable therapy provided her with more security and optimism for the future. See Fig 2 to see other terms used to describe the meaning participants ascribed to LAI-CAB/RPV. Participants also experienced a positive impact on their social lives. The reduced burden of medication allowed for more spontaneous and less restricted social interactions. Laura highlighted the transformative effect, saying, “I feel more like any other person now. I get the injection, and then I don’t have to think about it for two months”. The role of healthcare providers was crucial in the successful transition to LAI-CAB/RPV. Participants expressed gratitude for the support and guidance provided by their doctors and clinic staff. Ernesto highlighted the seamless process facilitated by his healthcare team, “The doctor and pharmacist coordinated everything. I didn’t have any issues with approval, and the process was smooth .” Laura also praised her healthcare providers, noting, “The staff here are excellent. They made sure everything was taken care of, and I felt supported throughout the transition”. The transition to LAI-CAB/RPV had a profound impact on participants’ quality of life. The convenience of reduced medication burden, improved adherence, and enhanced emotional well-being were consistently highlighted. Angélica summed up her experience, “It’s been a huge relief. I don’t have to worry about taking pills every day, and I feel more at peace”. Participants reported a significant improvement in their overall well-being, both physically and emotionally. Laura mentioned, “ Emotionally, I feel much better. I don’t have the daily reminder of my condition, and that has made a big difference in my life”. Ismael shared a similar experience, noting the positive impact on his mental health, “I feel much better since using the injectable. I don’t have the constant worry about my medication, and that has improved my emotional state”. Participants were asked to provide recommendations for others considering the transition to LAI-CAB/RPV. The advice was overwhelmingly positive, with many encouraging others to make the switch. Angélica advised, “ Don’t be afraid. It’s much easier than taking pills every day, and it has made a big difference in my life.” Laura emphasized the importance of staying informed and communicating with healthcare providers, “Seek information, talk to your doctor, and don’t be afraid to ask questions. This treatment has been a game-changer for me”. Participants also highlighted the importance of support from healthcare providers and the value of patient education. Ernesto suggested, “Make sure your healthcare team is supportive and that you understand the process. The transition can be smooth if you have the right information and support” .

The transition from oral ART to LAI-CAB/RPV in our study participants has demonstrated substantial benefits, including improved medication experience, enhanced quality of life, and reduced stigma. These findings are consistent with broader research, underscoring the potential of long-acting injectables to address the challenges associated with daily oral ART and to revolutionize the standard of care for people living with HIV. Future research and clinical practice should continue to explore the use and expand access to long-acting injectable ART to maximize its benefits for diverse populations living with HIV.

We conducted a qualitative study with a phenomenological approach to explore the lived experiences and perspectives of people living with HIV who transitioned from oral ART to LAI-CAB/RPV. Patients who were 21 years old or older, who transitioned from oral ART to LAI-CAB/RPV, and who had been on the injectable for at least six months were invited to be part of the study. Those cognitively impaired that could not provide informed consent were excluded from the study. The research was approved as exempt by the Nova Southeastern University Institutional Review Board on November 15, 2023 (protocol # 2023–576-NSU). This approval was valid and sufficient to conduct our study on our research site, and no additional step was needed. The study was conducted at Centro Ararat, a not-for-profit, Ryan White HIV/AIDS-funded clinic established in 2001, that offers primary health services in Ponce, San Juan, and Arecibo, Puerto Rico to over 1,200 people living with HIV. Centro Ararat worked the transition from oral ART to long-acting injectable as follows: after medical evaluation, the prescribing physician assesses eligibility criteria for switching to LAI- CAB/RPV. To qualify, patients must have maintained viral suppression for at least six months on their current oral antiretroviral regimen and must have no documented resistance to the prescribed agents. Eligible patients may initiate either an oral lead-in phase or transition directly to the injectable formulation. Once the decision to initiate LAI-CAB/RPV is made, the physician communicates the treatment plan to the multidisciplinary care team, which includes pharmacy, case management, nursing, and clinical coordinator. The case manager collaborates with the pharmacy department to assess insurance coverage for LAI-CAB/RPV. For patients with private insurance and specialty pharmacy benefits, medication is coordinated through the specialty pharmacy and delivered to the clinic. For those without private coverage, access is facilitated through public programs such as Medicaid or the AIDS Drug Assistance Program. Upon approval, delivery of the medication is scheduled, and the clinic receptionist coordinates the LAI-CAB/RPV administration appointment. The multidisciplinary team is responsible for ensuring timely receipt of medication every two months and for scheduling administration visits within the recommended timeframe to minimize the risk of delayed dosing and maintain therapeutic continuity. When the study took place, the clinic had only 49 patients who had transitioned to long-acting injectable ART. Purposeful sampling was used to recruit study participants. This strategy seeks to gain a deeper understanding of phenomena of interest by selecting rich cases, “from which one can learn a great deal about issues of central importance to the purpose of the research” [ 16 ]. Potential participants who were over 21 years old, who transitioned from oral ART to LAI-CAB/RPV, and who had been on the injectable for at least six months were invited to be part of the study. This six-month minimum was chosen since it allows sufficient time for participants to experience both the initial transition and medium-term adaptation to the injectable regimen. It was important to capture not only first impressions but also more sustained reflections on treatment integration into daily life. Study participants that met the inclusion criteria were invited to be part of the study by the staff of Centro Ararat. Once the participants agreed to be part of the study, an appointment for the face-to-face interview was made. At the moment of the interview, the first author confirmed that the participant indeed met the inclusion criteria and continued with the discussion of the written informed consent. After clarifying doubts and verifying the participant’s understanding, a signature of the informed consent was obtained. Considering the inclusion and exclusion criteria, 10 potential participants were invited to be part of the study and all of them agreed. The interview took place in a private space at Centro Ararat, a familiar and non-threatening environment for the study participants. Three of the authors developed the question guide: a pharmacy resident, a health educator with experience in qualitative studies and HIV, and a pharmacist specialized in HIV [R.V.P, G.S.S. & K.A.]. R.V.P is a Hispanic male with a pharmacy doctorate degree completing his postgraduate year one pharmacy residency. K.A. is a female pharmacist specialized in HIV with more than 15 years of experience in an HIV ambulatory care setting. G.S.S. is a Hispanic, female researcher with an educational background in public health and who has previously worked in a specialized HIV clinic in Puerto Rico. She has conducted various qualitative research projects and has had formal and informal training in conducting qualitative interviews and focus group. A panel of experts in HIV composed of academic external members and part of the research team reviewed the question guide, assessing its content alignment with the study’s purpose and the questions’ relevancy. The interview guide was later piloted with a potential participant. After the pilot, questions regarding receiving an HIV diagnosis were added. The question guide sought to elicit responses from the participants about their experiences as people living with HIV who transitioned from oral to long-acting injectable ART. Questions about HIV diagnosis, experience with oral ART, and experience and meaning of the transition to LAI-CAB/RPV ART were asked. Approval from the Nova Southeastern University Institutional Review Board was obtained before conducting the interviews. The first author conducted ten interviews from December 19, 2023, until March 3, 2024. The interviews lasted 30–40 minutes approximately and were voice-recorded and transcribed verbatim. Transcripts were checked for accuracy by the research team. Identifying information was removed from the transcripts to ensure confidentiality. Interviews were conducted in Spanish, the participants’ and researchers’ primary language. All the research files were kept in the principal investigator’s office in a locked cabinet. The voice recordings were transferred to the institutional computer of the first author, which is password protected. The recordings were deleted from the recorder to avoid a breach of confidentiality. A small sample size in Interpretative Phenomenological Analysis (IPA) is recommended [ 17 ]. After completing ten interviews, the research team noted that thematic recurrence was consistent across participants, suggesting that saturation had been achieved. This aligns with the methodological standards of IPA, which prioritizes depth of analysis over large sample sizes. Data analysis followed the IPA approach as outlined by Smith, Flowers [ 17 ]. The original Spanish interview transcripts were used for data analysis to avoid an additional level of interpretation and ensure accuracy, thereby respecting our participants’ voices. Each transcript was analyzed individually. The process began with multiple readings of the interview transcripts to immerse the researchers in the data and ensure the participants’ voices were central to the analysis. Detailed and comprehensive notes were made, capturing initial thoughts and reflections. These notes were then distilled into experiential statements to reduce the volume of detail while highlighting key points. Connections were mapped to identify patterns and relationships within the data, forming Personal Experiential Themes (PET) for each participant. This process was repeated for all transcripts, ensuring consistency and depth. Finally, the themes were synthesized across all participants to develop Group Experiential Themes (GET), identifying commonalities and differences in their experiences. Two GETs, receiving an HIV diagnosis and ART experience, were identified, along with different sub-themes within each of the GETs. Fig 1 shows a graphic representation of the data analysis. The GET and each sub-theme will be used to illustrate the study findings. English translations of the fragments from participants’ narratives will be included to support each GET and its sub-themes. Two authors (R.V.P. & G.S.S.), knowledgeable in English and Spanish and the Puerto Rican culture translated the finals quotes added in this manuscript. Study participants selected the fictional name used in this manuscript to protect their identity. Data analysis was conducted manually by three members of the research team (R.V.P., G.S.S. & F.B.). No codes were established a priori. Each of the coders worked independently, and after coding all the interviews a final meeting took place to discuss individual analysis and discuss discrepancies. When facing discrepancies in the coding, a discussion took place until consensus was reached. Anonymized excerpts of interview transcripts may be made available upon reasonable request to the corresponding author, subject to IRB approval and participant confidentiality agreements.