Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting

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The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). Methods This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV between June 2022 and May 2023. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 48 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was employed to estimate changes in clinical data from baseline. Results Thirty-eight male participants were enrolled. Viral suppression was maintained and no cases of virological failure were observed (estimated value:-10.9, 95%CI: -37.5–15.8]. Renal function improved (estimated value: -0.04, 95%CI: -0.07 – -0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased significantly after switching to CAB + RPV(estimated value: 6.6, 95%CI: 2.2–11.0). Conclusion Long-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being, but patient selection and monitoring to prevent HBV-related complications are important. Ethics and dissemination: This study was conducted as a single-center study and was reviewed and approved by the Ethics Review Committee of Osaka City General Hospital (approval number: 2210072). antiretroviral therapy long-acting antiretroviral therapy adherence cabotegravir rilpivirine Japanese Figures Figure 1 Figure 2 Figure 3 Introduction Since the introduction of antiretroviral therapy (ART), HIV medications have continuously improved. The risk of side effects has reduced, pill sizes have shrunk, and once-daily dosing, including a single-tablet regimen, has become the norm. Furthermore, the development of long-acting antiretroviral drugs represents a significant evolution in treatment. Long-acting ART, combining the new integrase inhibitor cabotegravir (CAB) with the established non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV), achieves an adequate blood concentration to suppress HIV with just one or two monthly injections (administered intramuscularly in the buttocks). Its antiviral effectiveness is similar to that of conventional antiretroviral regimens [ 1 – 3 ]. Improvements in treatment satisfaction have been reported among people living with HIV (PLWH) who switched from conventional to long-acting ART [ 4 ]. However, issues have been pointed out, such as the increased frequency of clinic visits, lack of anti-hepatitis B virus (HBV) activity [ 5 ], restricted convenience for PLWH on concomitant medications [ 6 ], and the emergence of drug-resistant mutations in clinical trials [ 2 , 3 , 7 ]. CAB + RPV is emerging as a novel ART option in Western countries. The US Food and Drug Administration approved a monthly injectable regimen in 2021 and a bimonthly regimen in 2022. In Japan, it was approved in March 2022 and made available in June 2022. Long-acting ART is not suitable for all patients with HIV, particularly untreated patients, and clinical research focuses on patients who have achieved virological suppression. The use of a long-acting injectable ART regimens eliminate the need for daily oral HIV medication and could lead to high patient satisfaction. However, few studies have evaluated antiviral effectiveness and treatment satisfaction of patients receiving long-acting ART in real-world clinical settings. Given this context, our study involved PLWH who switched from conventional to long-acting ART. We examined the antiviral effects of the long-acting ART and its impact on renal function, lipid metabolism, glucose metabolism, and treatment satisfaction. Patients and methods This single-center, prospective, cohort study focused on PLWH aged 18 or older. Participants were those who switched from conventional to long-acting ART between June 1, 2022, and May 31, 2023. The criteria for this switch included (1) HIV-RNA level < 50 copies/mL, (2) negative for HBV DNA, and (3) no resistance mutations related to RPV in past drug resistance tests. Patients were selected based on their informed consent after understanding the inclusion criteria. Before transitioning to long-acting ART, all patients were required to take an oral regimen of CAB and RPV for at least 4 weeks after switching from conventional ART to ensure no adverse effects. Clinical data extracted from electronic medical records included baseline information (age, gender, height), previous ART regimens, HIV-related status (CD4 positive T-lymphocyte count [CD4], HIV-RNA quantity [viral load: VL]), body weight, renal function markers (serum creatinine [Cre]), and random blood lipid markers (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides [TG]), and hemoglobin A1c (HbA1c) values. Blood tests were categorized as day 1 (just before changing from the oral CAB and RPV regimens), 4 weeks (just before switching to long-acting ART), and 8, 16, 24, 32, 40, and 48 weeks after switching to long-acting ART for analysis. Confirmed virological failure (CVF) was defined as a persistent VL above 200 copies/mL. Patient satisfaction with treatment was assessed using a 12-item questionnaire adapted from the original 10-item HIV Treatment Satisfaction Questionnaire (HIVTSQ), which was validated in an HIV-1 patient cohort [ 8 ]. This 12-item questionnaire, which was previously used in the ATLAS [ 1 ] and FLAIR [ 9 ] studies, was validated in the LATTE-2 study [ 10 ]. Two additional items were added to address the administration method of CAB + RPV LA (intramuscular injection). The items were: (1) “How easy or difficult have you been finding your treatment to be recently?” (2) “How satisfied are you with the amount of discomfort or pain involved with your present form of treatment?” HIVTSQ status version (HIVTSQs) instructs participants to rank their answers on a 6-point Likert scale ranging from 0 (“very dissatisfied”) to 6 (“very satisfied”). In contrast, the HIVTSQ change version (HIVTSQc) asks participants to compare the HIV therapy they were receiving before changing to long-acting ART with their current treatment and rank their answers from − 3 (“much less satisfied now”) to 3 (“much more satisfied now”). In both versions, item scores were added together to give a total aggregate summary score, with HIVTSQs ranging from 0 (“very dissatisfied”) to 66 (“very satisfied”), and HIVTSQc ranging from − 33 (“much less satisfied now”) to 33 (“much more satisfied now”). The HIVTSQs was administered on day 1 and at week 32, whereas the HIVTSQc was assessed only at week 32. Patient adherence was measured as the difference between the scheduled and actual injection dates, with 7 days around the planned date considered optimal. This study determined the proportion of patients who received injections within this timeframe. Additionally, this study was conducted as a single-center study and was reviewed and approved by the Ethics Review Committee of Osaka City General Hospital (approval number: 2210072). Statistical analysis The baseline characteristics of the participants were presented using frequencies (percentages) and medians (interquartile range [IQR]), as appropriate. A linear mixed-effects model was used to estimate changes in clinical data and treatment satisfaction from baseline. This model incorporates both participants and weeks as random effects. Changes from baseline were reported with 95% confidence intervals. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [ 11 ], a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria). EZR is an enhanced version of the R commander, specifically tailored to include statistical functions commonly used in biostatistics. Results This study included 38 male participants. The patients’ backgrounds are shown in Table 1 . The median age at treatment change was 46.5 years (IQR, 38–51.5 years), and the median body mass index (BMI) was 24.6 kg/m² (IQR, 23.1–26.9 kg/m²). Before the treatment change, the antiretroviral drug regimens comprised raltegravir (RAL) plus tenofovir alafenamide (TAF)/emtricitabine (FTC) in 8 patients (21%), dolutegravir (DTG)/lamivudine (3TC) in 7 patients (18%), bictegravir (BIC)/TAF/FTC in 6 patients (16%), DTG + TAF/FTC in 6 patients (16%), and darunavir/cobicistat (DRV/cobi)/TAF/FTC in 5 patients (13%). Regarding hepatitis B status, 17 patients (45%) were positive for hepatitis B surface (HBs) and core (HBc) antibodies (Ab), 5 (13%) for HBsAb alone, 3 (8%) for HBs antigen (Ag) with undetectable HBV DNA, and 13 (34%) were negative for HBsAg, HBcAb, and HBsAb. Table 1 Characteristics and measurements for PLWH in this study (N = 38) Variables Value Age (years), median [IQR] 46.5 [38–51.5] Height (cm), median [IQR] 168.5 [165.3–174] Body weight (kg), median [IQR] 71.5 [65.2–79.4] BMI (kg/m 2 ), median [IQR] 24.6 [23.1–26.9] Progressed to AIDS, n (%) 7 (18%) Duration of ART (months) 65.5 [49–119.5] History of treatment interruptions 4 (10.5%) Current ART RAL + TAF/FTC 8 (21%) DTG/3TC 7 (18%) BIC/TAF/FTC 6 (16%) DTG + TAF/FTC 6 (16%) DRV/cobi/TAF/FTC 5 (13%) Other regimens 6 (16%) Clinical data CD4 569 [455.3–889] VL 20 [20–24.8] Cre VL 0.91 [0.84–0.99] HDL-C 48 [41.2–54.8] LDL-C 117 [92–135] TG 138 [73–270] BW 71.5 [65.2–79.4] HIVTSQs score 54 [45.3–60.8] 3TC, lamivudine; ART, antiretroviral therapy; BIC, bictegravir; cobi, cobicistat; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; HBcAb, hepatitis B core antibody; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; IQR, interquartile range; RAL, raltegravir; TAF, tenofovir alafenamide, HDL-C, high-density lipoprotein cholesterol; HIVTSQ, HIV Treatment Satisfaction Questionnaire; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; VL, viral load. The changes in clinical data are shown in Fig. 1 . There were no cases of CVF, and no significant changes in CD4 counts (estimated value at 48 weeks: 23.9, 95% CI: -48.6–96.5) or VL (estimated value at 48 weeks: -10.9, 95%CI: -37.5–15.8) were observed. Five patients experienced treatment changes unrelated to CVF, including 3 with reactivation of HBV infection, 1 with acute hepatitis B, and 1 for personal reasons. All three patients with reactivation of hepatitis B infection were HBsAg-positive and HBV DNA-negative on blood tests prior to the change in long-acting therapy. The patient with acute hepatitis B was unvaccinated and negative for HBsAg, HBcAb, and HBsAb. The creatinine levels decreased at all observation points (estimated value at 48 weeks: -0.04, 95%CI: -0.07 – -0.01). No changes were observed in the HDL-C or TG levels; however, the LDL-C levels decreased after 8 (estimated value: -10.2, 95%CI: -18.9 – -1.4)and 16 weeks (estimated value: -13.5, 95%CI -22.6 – -4.4) and 16 weeks (estimated value: -13.5, 95%CI -22.6 – -4.4). No changes were observed in HbA1c levels; however, body weight was lower at 32 (estimated value: -0.87, 95%CI: -1.70 – -0.04) and 48 weeks (estimated value: -1.01, 95%CI: -2.01 – -0.01) than at baseline. Changes in treatment satisfaction are shown in Fig. 2 . HIVTSQs score was increased at 32 week (estimated value: 6.6, 95%CI: 2.2–11.0). Treatment satisfaction, as assessed using the HIVTSQc, showed positive scores across all items, with the median number of total score was 30 (IQR, 24.3–31.8). Patient adherence is shown in Fig. 3 . During the study period, 223 injections were administered, with 96% of the injections were administered during the dosing period, including 157 (70.4%) administered on the scheduled day, 46 (20.6%) administered 1–7 days late, and 11 (4.9%) administered 1–7 days early. Discussion In this study, no CVF was observed and most patients maintained viral suppression. In the ATLAS trial, a phase 3 study, patients who switched to monthly CAB + RPV injections showed similar efficacy and safety at 48 weeks as those who continued their current treatments after initially achieving virological suppression with conventional ART [ 1 ]. The ATLAS-2M trial, a phase 3b clinical trial comparing the efficacy and safety of the CAB + RPV bimonthly injection switch group with the CAB + RPV monthly injection switch group, also showed equivalent efficacy and safety at 48 weeks [ 2 ]. In the FLAIR trial, another phase 3 trial, patients who began with DTG/abacavir (ABC)/3TC and then switched to monthly CAB + RPV injections were compared with those who continued DTG/ABC/3TC. Both the groups demonstrated similar efficacy and safety at 96 weeks [ 3 ]. A combined analysis of the ATLAS, ATLAS-2M, and FLAIR trials examining factors related to CVF 48 weeks after initiating long-acting ART found that among 1,039 participants, 13 (1.3%) experienced CVF [ 12 ]. No single factor predicted CVF, but a combination of two or more factors—pro-virus RPV resistance-related mutations, HIV-1 subtype A6/A1, and BMI ≥ 30 kg/m²—resulted in a CVF rate of 25.7%. Although it is difficult to measure pro-virus resistance mutations and HIV-1 subtypes in clinical practice, E138A/G/K RPV resistance-related mutations were found in 8 of 1107 (0.72%) untreated Japanese PLWH [ 13 ]. The frequency of HIV-1 subtype A in the Japanese population is 15 of 3838 cases (0.4%) [ 14 ], and both E138A/G/K RPV resistance-related mutations and HIV-1 subtype A are relatively rare. The proportion of patients with a BMI ≥ 30 kg/m² among Japanese PLWH who started a tenofovir-containing regimen between 2002 and 2009 was reported as 8 of 494 cases (1.6%) [ 15 ]. However, recent reports indicate a link between ART and weight gain in PLWH, with significant weight gain observed after ART initiation compared with non-infected individuals [ 16 ], particularly among patients treated with integrase inhibitors and TAF/FTC [ 16 , 17 ]. A Swiss cohort study observed a rise in obesity among PLWH, with those having a BMI ≥ 30 kg/m² increasing from 4% in 2002 to 9% in 2012 and 12% in 2017 [ 18 ]. In our previous study of 543 treated PLWH, in which we used a body composition meter to assess the effect of ART, 218 patients (40.1%) were classified as obese (BMI ≥ 25 kg/m² and body fat percentage ≥ 20%), and 64 patients (11.8%) had a BMI ≥ 30 kg/m² [ 19 ]. Thus, obesity in PLWH is an important issue, and the proportion of obese patients with a BMI ≥ 30 kg/m² is expected to increase in Japan. In our study, five patients (13%) had a BMI ≥ 30 kg/m². Two patients switched from long-acting ART back to conventional ART due to HBV reactivation, but the remaining three continued treatment with long-acting ART without developing CVF. Further research is required to determine whether obesity is associated with CVF. A 2019 study of 2,389 HIV-positive adults from 25 countries, including 75 from Japan, assessed the factors affecting satisfaction with ART [ 20 ]. The study found that 36% of the Japanese participants viewed daily ART as a burden, 43% were reminded of their HIV status through daily intake, and 45% felt stressed by daily oral medication. Only 53% of Japanese participants reported no issues in managing their medications daily. The most sought-after improvements in HIV treatment were “reducing side effects” (53%), “minimizing long-term health impact” (48%), and “availability of long-acting treatments not requiring daily intake” (39%). This implies that a notable number of HIV-positive individuals are somewhat dissatisfied with their daily ART intake. In our hospital survey of PLWH [ 21 ], 16.2% were dissatisfied with conventional ART, while 54.9% preferred switching to long-acting ART. Although not all who wished to switch could do so, this indicates considerable interest among Japanese PLWH in long-acting ART. In this study, satisfaction with long-acting ART, as evaluated using the HIVTSQs/c, significantly increased. Adherence was high, with 96% of the injections administered on schedule. This suggests that long-acting ART may greatly enhance patient satisfaction, medication adherence, and overall quality of life. In this study, an improvement in Cre levels was observed after switching to a long-acting ART. Drugs such as cobi, ritonavir (rtv), RPV, DTG, and BIC inhibit transporters, leading to decreased creatinine secretion from the renal tubules. Thus, an initial increase in serum creatinine and a decrease in creatinine clearance is observed. Cobi and DTG do not alter the true glomerular filtration rate [ 22 , 23 ]. The apparent improvement in renal function due to the decrease in Cre levels can be attributed to the switch from conventional to a long-acting ART. Conversely, TAF, commonly used in conventional ART, is a prodrug of tenofovir disoproxil fumarate (TDF) and is believed to reduce the tubular toxicity associated with TDF [ 24 , 25 ]. Therefore, TAF is a new treatment option for patients with reduced renal function. However, the US Department of Health and Human Services guidelines [ 26 ] recommend careful monitoring when switching from TDF to TAF, owing to the unclear long-term effects on patients with a history of renal disease, including proximal tubular injury, even though the switch is associated with improvements in proteinuria and renal biomarkers. Renal function recovery has been reported in patients with chronic kidney failure who switched to an NRTI-sparing regimen [ 27 , 28 ]; however, the true improvement in renal function in this study is unclear because of the lack of measurements of urinary markers such as cystatin C and beta-2 microglobulin. Further case accumulation and evaluation of renal function using urinary markers are required to understand the impact of long-acting ART on renal function. This study has a few limitations. First, it involved a relatively small and homogeneous group of 38 male participants, potentially limiting the generalizability of the findings. A larger and more diverse sample would likely yield more comprehensive insights, applicable to a broader population. Second, being conducted at a single center, the study may reflect particular local practices or patient demographics. Multi-center studies could provide a broader perspective and help reduce the biases associated with single-center research. Third, the absence of a comparative control group in this study design is a notable limitation. Including a control group receiving standard treatment would have enhanced our ability to directly link the observed outcomes to the long-acting therapy. Despite the limitations, the strength of this study is distinguished by its real-world clinical setting, providing practical insights. The extensive data collection over a significant period adds depth to our findings. Importantly, the focus on patient satisfaction introduces a valuable dimension, reflecting a holistic approach to assessing therapy effectiveness. Conclusion In conclusion, in patients who switched from conventional to long-acting ART, no CVF was observed, and experienced increased treatment satisfaction. Despite limitations, such as the small and homogeneous nature of the participant group and the absence of a control group, our findings underscore the potential of long-acting therapy in maintaining viral suppression and enhancing patient satisfaction and quality of life. A BMI ≥ 30 kg/m² has been reported as a predictor of virological treatment failure in injection regimens, and an increase in obese PLWH is expected in Japan. Further studies are needed to determine whether obesity alone can lead to treatment failure. Treatment satisfaction, as assessed using the HIVTSQs and HIVTSQc, improved, suggesting that injection regimens could contribute to patient satisfaction, medication adherence, and enhanced quality of life. Future research, involving larger and more diverse cohorts and conducted across multiple centers, is essential to corroborate these findings and broaden our understanding of the role of long-acting therapy in HIV treatment. Abbreviations 3TC, lamivudine; Ab, antibody; ABC, abacavir; Ag, antigen; ART, antiretroviral therapy; BMI, body mass index; CAB, cabotegravir; Cre, serum creatinine; CVF, confirmed virological failure; DTG, dolutegravir; FTC, emtricitabine; HbA1C, hemoglobin A1c; HBcAb, hepatitis B core antibody; HBsAb, Hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HDL-C, high-density lipoprotein cholesterol; HIVTSQ, HIV Treatment Satisfaction Questionnaire; LDL-C, low-density lipoprotein cholesterol; RPV, rilpivirine; rtv, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; TG, triglycerides; VL, viral load. Declarations Ethics approval and consent to participate The study was approved by the Ethics Review Committee of Osaka City General Medical Center (Approval Number: 2210072). The study was conducted in compliance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the patient to participate in the study. Consent for publication Not applicable Availability of data and materials Raw data were generated at Osaka City General Hospital. Derived data supporting the findings of this study are available from the corresponding author K.K. on request. Competing interests The authors declare that they have no competing interests Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author contributions K.K. contributed to the study design, conducted the literature review, wrote the manuscript, and was responsible for the final decision to submit the manuscript. D.O. revised the manuscript and provided valuable intellectual content. M.O., Y.K., and M.S. contributed to the data acquisition from each institution. M.S. supervised the conduct of this study. All authors reviewed the draft manuscript and critically revised it critically for intellectual content. All authors approved the final version of the submitted manuscript. Acknowledgments Editorial support, in the form of medical writing, collating author comments, copyediting, fact-checking, and referencing, was provided by Editage, Cactus Communications. Declaration of competing interests None declared. References Swindells S, Andrade-Villanueva JF, Richmond GJ, Rizzardini G, Baumgarten A, Masiá M, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med 2020;382:1112 – 23. https://doi.org/10.1056/NEJMoa1904398. Overton ET, Richmond G, Rizzardini G, Jaeger H, Orrell C, Nagimova F, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. 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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents with HIV. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new-guidelines. [Accessed 22 June 2022]. Fontecha M, Monsalvo M, Rodriguez-Sagrado MA, Vivancos MJ, Moreno A, Casado JL. Long-term improvement in renal, bone, lipid parameters, and CD4/CD8 ratio in HIV-infected patients switching to a dual therapy with lamivudine plus boosted darunavir. Infect Dis (Lond) 2019;51:293 – 8. https://doi.org/10.1080/23744235.2018.1554908. Jabłonowska E, Pulik P, Kalinowska A, Gąsiorowski J, Parczewski M, Bociąga-Jasik M, et al. Efficacy and safety of nucleoside-sparing regimen based on raltegravir and ritonavir-boosted darunavir in HIV-1-infected treatment-experienced patients. J Med Virol 2017;89:2122 – 9. https://doi.org/10.1002/jmv.24826. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Sep, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted Reviews received at journal 30 May, 2024 Reviewers agreed at journal 23 May, 2024 Reviews received at journal 15 May, 2024 Reviewers agreed at journal 01 May, 2024 Reviewers agreed at journal 02 Apr, 2024 Reviewers invited by journal 27 Mar, 2024 Editor assigned by journal 26 Mar, 2024 Editor invited by journal 04 Mar, 2024 Submission checks completed at journal 04 Mar, 2024 First submitted to journal 19 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3971672","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":276488579,"identity":"bd057dd7-192a-48e8-af74-1d8f1679b650","order_by":0,"name":"Keiji Konishi","email":"data:image/png;base64,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","orcid":"","institution":"Osaka University","correspondingAuthor":true,"prefix":"","firstName":"Keiji","middleName":"","lastName":"Konishi","suffix":""},{"id":276488580,"identity":"b7d40324-989c-4e5a-a0be-f16f8300449c","order_by":1,"name":"Daisuke Onozuka","email":"","orcid":"","institution":"Osaka University","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Onozuka","suffix":""},{"id":276488581,"identity":"ffc3ff84-be75-4ab4-b2f5-525e8a416664","order_by":2,"name":"Moeka Ookubo","email":"","orcid":"","institution":"Osaka City General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Moeka","middleName":"","lastName":"Ookubo","suffix":""},{"id":276488582,"identity":"e48018af-6c13-481a-89ff-69878e0f488e","order_by":3,"name":"Yu Kasamatsu","email":"","orcid":"","institution":"Osaka City General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Kasamatsu","suffix":""},{"id":276488583,"identity":"3dc90d29-4d95-4ad9-821c-d0ead1df94d6","order_by":4,"name":"Michinori Shirano","email":"","orcid":"","institution":"Osaka City General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Michinori","middleName":"","lastName":"Shirano","suffix":""}],"badges":[],"createdAt":"2024-02-20 04:50:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3971672/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3971672/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-024-09904-x","type":"published","date":"2024-09-16T15:56:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52105182,"identity":"b1f5dbb1-1c79-4b2e-9d51-e8fe8b1d71db","added_by":"auto","created_at":"2024-03-06 19:26:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1048382,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in clinical data after switching from conventional to long-acting antiretroviral therapy\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3971672/v1/474509f788eae1b095c7728f.png"},{"id":52105179,"identity":"8a1973cc-7366-4dea-aec0-b8e1569d96b6","added_by":"auto","created_at":"2024-03-06 19:26:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":643071,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment satisfaction before and after switching from conventional to long-acting antiretroviral therapy\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3971672/v1/d8fc7ff2f84fbd135c8462a9.png"},{"id":52105183,"identity":"deb0fe58-abc9-4517-9ebd-6b7b626bfac2","added_by":"auto","created_at":"2024-03-06 19:26:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":381768,"visible":true,"origin":"","legend":"\u003cp\u003eAdherence to the injection schedule among patients receiving long-acting antiretroviral therapy\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3971672/v1/81ffbc9a2e601fc831f1238e.png"},{"id":65108891,"identity":"492ecd3a-562e-4902-8454-ea33877bb5c7","added_by":"auto","created_at":"2024-09-23 17:29:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1877293,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3971672/v1/43431c5a-9498-4fe3-974a-e1da3aa53733.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSince the introduction of antiretroviral therapy (ART), HIV medications have continuously improved. The risk of side effects has reduced, pill sizes have shrunk, and once-daily dosing, including a single-tablet regimen, has become the norm. Furthermore, the development of long-acting antiretroviral drugs represents a significant evolution in treatment. Long-acting ART, combining the new integrase inhibitor cabotegravir (CAB) with the established non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV), achieves an adequate blood concentration to suppress HIV with just one or two monthly injections (administered intramuscularly in the buttocks). Its antiviral effectiveness is similar to that of conventional antiretroviral regimens [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Improvements in treatment satisfaction have been reported among people living with HIV (PLWH) who switched from conventional to long-acting ART [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, issues have been pointed out, such as the increased frequency of clinic visits, lack of anti-hepatitis B virus (HBV) activity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], restricted convenience for PLWH on concomitant medications [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and the emergence of drug-resistant mutations in clinical trials [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCAB\u0026thinsp;+\u0026thinsp;RPV is emerging as a novel ART option in Western countries. The US Food and Drug Administration approved a monthly injectable regimen in 2021 and a bimonthly regimen in 2022. In Japan, it was approved in March 2022 and made available in June 2022. Long-acting ART is not suitable for all patients with HIV, particularly untreated patients, and clinical research focuses on patients who have achieved virological suppression. The use of a long-acting injectable ART regimens eliminate the need for daily oral HIV medication and could lead to high patient satisfaction. However, few studies have evaluated antiviral effectiveness and treatment satisfaction of patients receiving long-acting ART in real-world clinical settings.\u003c/p\u003e \u003cp\u003eGiven this context, our study involved PLWH who switched from conventional to long-acting ART. We examined the antiviral effects of the long-acting ART and its impact on renal function, lipid metabolism, glucose metabolism, and treatment satisfaction.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThis single-center, prospective, cohort study focused on PLWH aged 18 or older. Participants were those who switched from conventional to long-acting ART between June 1, 2022, and May 31, 2023. The criteria for this switch included (1) HIV-RNA level\u0026thinsp;\u0026lt;\u0026thinsp;50 copies/mL, (2) negative for HBV DNA, and (3) no resistance mutations related to RPV in past drug resistance tests. Patients were selected based on their informed consent after understanding the inclusion criteria. Before transitioning to long-acting ART, all patients were required to take an oral regimen of CAB and RPV for at least 4 weeks after switching from conventional ART to ensure no adverse effects. Clinical data extracted from electronic medical records included baseline information (age, gender, height), previous ART regimens, HIV-related status (CD4 positive T-lymphocyte count [CD4], HIV-RNA quantity [viral load: VL]), body weight, renal function markers (serum creatinine [Cre]), and random blood lipid markers (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides [TG]), and hemoglobin A1c (HbA1c) values. Blood tests were categorized as day 1 (just before changing from the oral CAB and RPV regimens), 4 weeks (just before switching to long-acting ART), and 8, 16, 24, 32, 40, and 48 weeks after switching to long-acting ART for analysis. Confirmed virological failure (CVF) was defined as a persistent VL above 200 copies/mL. Patient satisfaction with treatment was assessed using a 12-item questionnaire adapted from the original 10-item HIV Treatment Satisfaction Questionnaire (HIVTSQ), which was validated in an HIV-1 patient cohort [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This 12-item questionnaire, which was previously used in the ATLAS [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] and FLAIR [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] studies, was validated in the LATTE-2 study [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Two additional items were added to address the administration method of CAB\u0026thinsp;+\u0026thinsp;RPV LA (intramuscular injection). The items were:\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e(1) \u0026ldquo;How easy or difficult have you been finding your treatment to be recently?\u0026rdquo;\u003c/p\u003e \u003cp\u003e(2) \u0026ldquo;How satisfied are you with the amount of discomfort or pain involved with your present form of treatment?\u0026rdquo;\u003c/p\u003e \u003cp\u003eHIVTSQ status version (HIVTSQs) instructs participants to rank their answers on a 6-point Likert scale ranging from 0 (\u0026ldquo;very dissatisfied\u0026rdquo;) to 6 (\u0026ldquo;very satisfied\u0026rdquo;). In contrast, the HIVTSQ change version (HIVTSQc) asks participants to compare the HIV therapy they were receiving before changing to long-acting ART with their current treatment and rank their answers from \u0026minus;\u0026thinsp;3 (\u0026ldquo;much less satisfied now\u0026rdquo;) to 3 (\u0026ldquo;much more satisfied now\u0026rdquo;). In both versions, item scores were added together to give a total aggregate summary score, with HIVTSQs ranging from 0 (\u0026ldquo;very dissatisfied\u0026rdquo;) to 66 (\u0026ldquo;very satisfied\u0026rdquo;), and HIVTSQc ranging from \u0026minus;\u0026thinsp;33 (\u0026ldquo;much less satisfied now\u0026rdquo;) to 33 (\u0026ldquo;much more satisfied now\u0026rdquo;). The HIVTSQs was administered on day 1 and at week 32, whereas the HIVTSQc was assessed only at week 32. Patient adherence was measured as the difference between the scheduled and actual injection dates, with 7 days around the planned date considered optimal. This study determined the proportion of patients who received injections within this timeframe. Additionally, this study was conducted as a single-center study and was reviewed and approved by the Ethics Review Committee of Osaka City General Hospital (approval number: 2210072).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe baseline characteristics of the participants were presented using frequencies (percentages) and medians (interquartile range [IQR]), as appropriate. A linear mixed-effects model was used to estimate changes in clinical data and treatment satisfaction from baseline. This model incorporates both participants and weeks as random effects. Changes from baseline were reported with 95% confidence intervals. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria). EZR is an enhanced version of the R commander, specifically tailored to include statistical functions commonly used in biostatistics.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThis study included 38 male participants. The patients\u0026rsquo; backgrounds are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age at treatment change was 46.5 years (IQR, 38\u0026ndash;51.5 years), and the median body mass index (BMI) was 24.6 kg/m\u0026sup2; (IQR, 23.1\u0026ndash;26.9 kg/m\u0026sup2;). Before the treatment change, the antiretroviral drug regimens comprised raltegravir (RAL) plus tenofovir alafenamide (TAF)/emtricitabine (FTC) in 8 patients (21%), dolutegravir (DTG)/lamivudine (3TC) in 7 patients (18%), bictegravir (BIC)/TAF/FTC in 6 patients (16%), DTG\u0026thinsp;+\u0026thinsp;TAF/FTC in 6 patients (16%), and darunavir/cobicistat (DRV/cobi)/TAF/FTC in 5 patients (13%). Regarding hepatitis B status, 17 patients (45%) were positive for hepatitis B surface (HBs) and core (HBc) antibodies (Ab), 5 (13%) for HBsAb alone, 3 (8%) for HBs antigen (Ag) with undetectable HBV DNA, and 13 (34%) were negative for HBsAg, HBcAb, and HBsAb.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics and measurements for PLWH in this study (N\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.5 [38\u0026ndash;51.5]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm), median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e168.5 [165.3\u0026ndash;174]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody weight (kg), median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.5 [65.2\u0026ndash;79.4]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e), median [IQR]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.6 [23.1\u0026ndash;26.9]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgressed to AIDS, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of ART (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.5 [49\u0026ndash;119.5]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of treatment interruptions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRAL\u0026thinsp;+\u0026thinsp;TAF/FTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (21%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDTG/3TC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBIC/TAF/FTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDTG\u0026thinsp;+\u0026thinsp;TAF/FTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDRV/cobi/TAF/FTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (13%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther regimens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e569 [455.3\u0026ndash;889]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 [20\u0026ndash;24.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCre VL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.91 [0.84\u0026ndash;0.99]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL-C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 [41.2\u0026ndash;54.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL-C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117 [92\u0026ndash;135]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e138 [73\u0026ndash;270]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBW\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.5 [65.2\u0026ndash;79.4]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIVTSQs score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 [45.3\u0026ndash;60.8]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e3TC, lamivudine; ART, antiretroviral therapy; BIC, bictegravir; cobi, cobicistat; DRV, darunavir; DTG, dolutegravir; FTC, emtricitabine; HBcAb, hepatitis B core antibody; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; IQR, interquartile range; RAL, raltegravir; TAF, tenofovir alafenamide, HDL-C, high-density lipoprotein cholesterol; HIVTSQ, HIV Treatment Satisfaction Questionnaire; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; VL, viral load.\u003c/p\u003e \u003cp\u003eThe changes in clinical data are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were no cases of CVF, and no significant changes in CD4 counts (estimated value at 48 weeks: 23.9, 95% CI: -48.6\u0026ndash;96.5) or VL (estimated value at 48 weeks: -10.9, 95%CI: -37.5\u0026ndash;15.8) were observed. Five patients experienced treatment changes unrelated to CVF, including 3 with reactivation of HBV infection, 1 with acute hepatitis B, and 1 for personal reasons. All three patients with reactivation of hepatitis B infection were HBsAg-positive and HBV DNA-negative on blood tests prior to the change in long-acting therapy. The patient with acute hepatitis B was unvaccinated and negative for HBsAg, HBcAb, and HBsAb. The creatinine levels decreased at all observation points (estimated value at 48 weeks: -0.04, 95%CI: -0.07 \u0026ndash; -0.01). No changes were observed in the HDL-C or TG levels; however, the LDL-C levels decreased after 8 (estimated value: -10.2, 95%CI: -18.9 \u0026ndash; -1.4)and 16 weeks (estimated value: -13.5, 95%CI -22.6 \u0026ndash; -4.4) and 16 weeks (estimated value: -13.5, 95%CI -22.6 \u0026ndash; -4.4). No changes were observed in HbA1c levels; however, body weight was lower at 32 (estimated value: -0.87, 95%CI: -1.70 \u0026ndash; -0.04) and 48 weeks (estimated value: -1.01, 95%CI: -2.01 \u0026ndash; -0.01) than at baseline. Changes in treatment satisfaction are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. HIVTSQs score was increased at 32 week (estimated value: 6.6, 95%CI: 2.2\u0026ndash;11.0). Treatment satisfaction, as assessed using the HIVTSQc, showed positive scores across all items, with the median number of total score was 30 (IQR, 24.3\u0026ndash;31.8).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatient adherence is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. During the study period, 223 injections were administered, with 96% of the injections were administered during the dosing period, including 157 (70.4%) administered on the scheduled day, 46 (20.6%) administered 1\u0026ndash;7 days late, and 11 (4.9%) administered 1\u0026ndash;7 days early.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, no CVF was observed and most patients maintained viral suppression. In the ATLAS trial, a phase 3 study, patients who switched to monthly CAB\u0026thinsp;+\u0026thinsp;RPV injections showed similar efficacy and safety at 48 weeks as those who continued their current treatments after initially achieving virological suppression with conventional ART [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The ATLAS-2M trial, a phase 3b clinical trial comparing the efficacy and safety of the CAB\u0026thinsp;+\u0026thinsp;RPV bimonthly injection switch group with the CAB\u0026thinsp;+\u0026thinsp;RPV monthly injection switch group, also showed equivalent efficacy and safety at 48 weeks [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In the FLAIR trial, another phase 3 trial, patients who began with DTG/abacavir (ABC)/3TC and then switched to monthly CAB\u0026thinsp;+\u0026thinsp;RPV injections were compared with those who continued DTG/ABC/3TC. Both the groups demonstrated similar efficacy and safety at 96 weeks [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA combined analysis of the ATLAS, ATLAS-2M, and FLAIR trials examining factors related to CVF 48 weeks after initiating long-acting ART found that among 1,039 participants, 13 (1.3%) experienced CVF [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. No single factor predicted CVF, but a combination of two or more factors\u0026mdash;pro-virus RPV resistance-related mutations, HIV-1 subtype A6/A1, and BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2;\u0026mdash;resulted in a CVF rate of 25.7%. Although it is difficult to measure pro-virus resistance mutations and HIV-1 subtypes in clinical practice, E138A/G/K RPV resistance-related mutations were found in 8 of 1107 (0.72%) untreated Japanese PLWH [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The frequency of HIV-1 subtype A in the Japanese population is 15 of 3838 cases (0.4%) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and both E138A/G/K RPV resistance-related mutations and HIV-1 subtype A are relatively rare. The proportion of patients with a BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2; among Japanese PLWH who started a tenofovir-containing regimen between 2002 and 2009 was reported as 8 of 494 cases (1.6%) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, recent reports indicate a link between ART and weight gain in PLWH, with significant weight gain observed after ART initiation compared with non-infected individuals [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], particularly among patients treated with integrase inhibitors and TAF/FTC [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A Swiss cohort study observed a rise in obesity among PLWH, with those having a BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2; increasing from 4% in 2002 to 9% in 2012 and 12% in 2017 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our previous study of 543 treated PLWH, in which we used a body composition meter to assess the effect of ART, 218 patients (40.1%) were classified as obese (BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u0026sup2; and body fat percentage\u0026thinsp;\u0026ge;\u0026thinsp;20%), and 64 patients (11.8%) had a BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2; [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Thus, obesity in PLWH is an important issue, and the proportion of obese patients with a BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2; is expected to increase in Japan. In our study, five patients (13%) had a BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2;. Two patients switched from long-acting ART back to conventional ART due to HBV reactivation, but the remaining three continued treatment with long-acting ART without developing CVF. Further research is required to determine whether obesity is associated with CVF.\u003c/p\u003e \u003cp\u003eA 2019 study of 2,389 HIV-positive adults from 25 countries, including 75 from Japan, assessed the factors affecting satisfaction with ART [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The study found that 36% of the Japanese participants viewed daily ART as a burden, 43% were reminded of their HIV status through daily intake, and 45% felt stressed by daily oral medication. Only 53% of Japanese participants reported no issues in managing their medications daily. The most sought-after improvements in HIV treatment were \u0026ldquo;reducing side effects\u0026rdquo; (53%), \u0026ldquo;minimizing long-term health impact\u0026rdquo; (48%), and \u0026ldquo;availability of long-acting treatments not requiring daily intake\u0026rdquo; (39%). This implies that a notable number of HIV-positive individuals are somewhat dissatisfied with their daily ART intake. In our hospital survey of PLWH [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], 16.2% were dissatisfied with conventional ART, while 54.9% preferred switching to long-acting ART. Although not all who wished to switch could do so, this indicates considerable interest among Japanese PLWH in long-acting ART. In this study, satisfaction with long-acting ART, as evaluated using the HIVTSQs/c, significantly increased. Adherence was high, with 96% of the injections administered on schedule. This suggests that long-acting ART may greatly enhance patient satisfaction, medication adherence, and overall quality of life.\u003c/p\u003e \u003cp\u003eIn this study, an improvement in Cre levels was observed after switching to a long-acting ART. Drugs such as cobi, ritonavir (rtv), RPV, DTG, and BIC inhibit transporters, leading to decreased creatinine secretion from the renal tubules. Thus, an initial increase in serum creatinine and a decrease in creatinine clearance is observed. Cobi and DTG do not alter the true glomerular filtration rate [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The apparent improvement in renal function due to the decrease in Cre levels can be attributed to the switch from conventional to a long-acting ART. Conversely, TAF, commonly used in conventional ART, is a prodrug of tenofovir disoproxil fumarate (TDF) and is believed to reduce the tubular toxicity associated with TDF [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Therefore, TAF is a new treatment option for patients with reduced renal function. However, the US Department of Health and Human Services guidelines [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] recommend careful monitoring when switching from TDF to TAF, owing to the unclear long-term effects on patients with a history of renal disease, including proximal tubular injury, even though the switch is associated with improvements in proteinuria and renal biomarkers. Renal function recovery has been reported in patients with chronic kidney failure who switched to an NRTI-sparing regimen [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]; however, the true improvement in renal function in this study is unclear because of the lack of measurements of urinary markers such as cystatin C and beta-2 microglobulin. Further case accumulation and evaluation of renal function using urinary markers are required to understand the impact of long-acting ART on renal function.\u003c/p\u003e \u003cp\u003eThis study has a few limitations. First, it involved a relatively small and homogeneous group of 38 male participants, potentially limiting the generalizability of the findings. A larger and more diverse sample would likely yield more comprehensive insights, applicable to a broader population. Second, being conducted at a single center, the study may reflect particular local practices or patient demographics. Multi-center studies could provide a broader perspective and help reduce the biases associated with single-center research. Third, the absence of a comparative control group in this study design is a notable limitation. Including a control group receiving standard treatment would have enhanced our ability to directly link the observed outcomes to the long-acting therapy. Despite the limitations, the strength of this study is distinguished by its real-world clinical setting, providing practical insights. The extensive data collection over a significant period adds depth to our findings. Importantly, the focus on patient satisfaction introduces a valuable dimension, reflecting a holistic approach to assessing therapy effectiveness.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, in patients who switched from conventional to long-acting ART, no CVF was observed, and experienced increased treatment satisfaction. Despite limitations, such as the small and homogeneous nature of the participant group and the absence of a control group, our findings underscore the potential of long-acting therapy in maintaining viral suppression and enhancing patient satisfaction and quality of life. A BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2; has been reported as a predictor of virological treatment failure in injection regimens, and an increase in obese PLWH is expected in Japan. Further studies are needed to determine whether obesity alone can lead to treatment failure. Treatment satisfaction, as assessed using the HIVTSQs and HIVTSQc, improved, suggesting that injection regimens could contribute to patient satisfaction, medication adherence, and enhanced quality of life. Future research, involving larger and more diverse cohorts and conducted across multiple centers, is essential to corroborate these findings and broaden our understanding of the role of long-acting therapy in HIV treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e3TC, lamivudine; Ab, antibody; ABC, abacavir; Ag, antigen; ART, antiretroviral therapy; BMI, body mass index; CAB, cabotegravir; Cre, serum creatinine; CVF, confirmed virological failure; DTG, dolutegravir; FTC, emtricitabine; HbA1C, hemoglobin A1c; HBcAb, hepatitis B core antibody; HBsAb, Hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HDL-C, high-density lipoprotein cholesterol; HIVTSQ, HIV Treatment Satisfaction Questionnaire; LDL-C, low-density lipoprotein cholesterol; RPV, rilpivirine; rtv, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; TG, triglycerides; VL, viral load.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by\u0026nbsp;the\u0026nbsp;Ethics Review Committee of Osaka City General Medical Center (Approval Number: 2210072).\u0026nbsp;The study was conducted in compliance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the patient to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRaw data were generated at Osaka City General Hospital. Derived data supporting the findings of this study are available from the corresponding author K.K. on request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK.K. contributed to the study design, conducted the literature review, wrote the manuscript, and was responsible for the final decision to submit the manuscript. D.O. revised the manuscript and provided valuable intellectual content. M.O., Y.K., and M.S. contributed to the data acquisition from each institution. M.S. supervised the conduct of this study. All authors reviewed the draft manuscript and critically revised it critically for intellectual content. All authors approved the final version of the submitted manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEditorial support, in the form of medical writing, collating author comments, copyediting, fact-checking, and referencing, was provided by Editage, Cactus Communications.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eDeclaration of competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSwindells S, Andrade-Villanueva JF, Richmond GJ, Rizzardini G, Baumgarten A, Masi\u0026aacute; M, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med 2020;382:1112 \u0026ndash; 23. https://doi.org/10.1056/NEJMoa1904398.\u003c/li\u003e\n\u003cli\u003eOverton ET, Richmond G, Rizzardini G, Jaeger H, Orrell C, Nagimova F, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet 2021;396:1994 \u0026ndash; 2005. https://doi.org/10.1016/s0140-6736(20)32666-0.\u003c/li\u003e\n\u003cli\u003eOrkin C, Oka S, Philibert P, Brinson C, Bassa A, Gusev D, et al. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV 2021;8:e185 \u0026ndash; 96. https://doi.org/10.1016/s2352-3018(20)30340-4.\u003c/li\u003e\n\u003cli\u003eMurray M, Antela A, Mills A, Huang J, J\u0026auml;ger H, Bernal E, et al. 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Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. J Acquir Immune Defic Syndr (1999) 2020;85:498.\u003c/li\u003e\n\u003cli\u003eWoodcock A, Bradley C. Validation of the revised 10-item HIV Treatment Satisfaction Questionnaire status version and new change version. Value Health 2006;9:320 \u0026ndash; 33. https://doi.org/10.1111/j.1524-4733.2006.00121.x.\u003c/li\u003e\n\u003cli\u003eOrkin C, Arasteh K, G\u0026oacute;rgolas Hern\u0026aacute;ndez-Mora M, Pokrovsky V, Overton ET, Girard P-M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 Infection. N Eng J Med 2020;382:1124 \u0026ndash; 35. https://doi.org/10.1056/NEJMoa1909512.\u003c/li\u003e\n\u003cli\u003eMargolis DA, Gonzalez-Garcia J, Stellbrink HJ, Eron JJ, Yazdanpanah Y, Podzamczer D, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet 2017;390:1499 \u0026ndash; 510. https://doi.org/10.1016/s0140-6736(17)31917-7.\u003c/li\u003e\n\u003cli\u003eKanda Y. Investigation of the freely available easy-to-use software \u0026lsquo;EZR\u0026rsquo; for medical statistics. Bone Marrow Transplant 2013;48:452 \u0026ndash; 8. https://doi.org/10.1038/bmt.2012.244.\u003c/li\u003e\n\u003cli\u003eCutrell AG, Schapiro JM, Perno CF, Kuritzkes DR, Quercia R, Patel P, et al. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis. AIDS 2021;35:1333 \u0026ndash; 42. https://doi.org/10.1097/qad.0000000000002883.\u003c/li\u003e\n\u003cli\u003eGatanaga H, Murakoshi H, Hachiya A, Hayashida T, Chikata T, Ode H, et al. Naturally selected rilpivirine-resistant HIV-1 variants by host cellular immunity. Clin Infect Dis 2013;57:1051 \u0026ndash; 5. https://doi.org/10.1093/cid/cit430.\u003c/li\u003e\n\u003cli\u003eHattori J, Shiino T, Gatanaga H, Mori H, Minami R, Uchida K, et al. Characteristics of transmitted drug-resistant HIV-1 in recently infected treatment-naive patients in Japan. J Acquir Immune Defic Syndr 2016;71:367 \u0026ndash; 73. https://doi.org/10.1097/qai.0000000000000861.\u003c/li\u003e\n\u003cli\u003eNishijima T, Komatsu H, Gatanaga H, Aoki T, Watanabe K, Kinai E, et al. Impact of small body weight on tenofovir-associated renal dysfunction in HIV-infected patients: a retrospective cohort study of Japanese patients. PLoS One 2011;6:e22661. https://doi.org/10.1371/journal.pone.0022661.\u003c/li\u003e\n\u003cli\u003eSax PE, Erlandson KM, Lake JE, McComsey GA, Orkin C, Esser S, et al. Weight gain following initiation of antiretroviral therapy: Risk factors in randomized comparative clinical trials. Clin Infect Dis 2020;71:1379 \u0026ndash; 89. https://doi.org/10.1093/cid/ciz999.\u003c/li\u003e\n\u003cli\u003eVenter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med 2019;381:803 \u0026ndash; 15. https://doi.org/10.1056/NEJMoa1902824.\u003c/li\u003e\n\u003cli\u003eBarcel\u0026oacute; C, Guidi M, Thorball CW, Hammer C, Chaouch A, Scherrer AU, et al. Impact of genetic and nongenetic factors on body mass index and waist-hip ratio change in HIV-infected individuals initiating antiretroviral therapy. Open Forum Infect Dis 2020;7:ofz464. https://doi.org/10.1093/ofid/ofz464.\u003c/li\u003e\n\u003cli\u003eKonishi K, Nakagawa H, Asaoka T, Kasamatsu Y, Goto T, Shirano M. Effect of antiretroviral therapy on body composition in patients living with human immunodeficiency virus: An observational study. Preprint (Version 1) available at Research Square 2023. https://doi.org/10.21203/rs.3.rs-3284485/v1.\u003c/li\u003e\n\u003cli\u003eKoga I, Wakatabe R, Okamoto N, Sasai A, Kambara K, Maldonado A, et al. Factors associated with treatment satisfaction among people living with HIV in Japan and other selected countries: Examination of the intertwined roles of medication, patient, and provider characteristics. AIDS Behav 2022;26:1633 \u0026ndash; 51. https://doi.org/10.1007/s10461-021-03515-2.\u003c/li\u003e\n\u003cli\u003eKonishi K, Nakagawa H, Morita R, Yawata R, Asaoka T, Iida K, et al. Questionnaire survey on long-acting injectable antiretroviral therapy among people living with HIV. The Journal of AIDS Research 2023;25:165 \u0026ndash; 71.\u003c/li\u003e\n\u003cli\u003eGerman P, Liu HC, Szwarcberg J, Hepner M, Andrews J, Kearney BP, et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr 2012;61:32 \u0026ndash; 40. https://doi.org/10.1097/QAI.0b013e3182645648.\u003c/li\u003e\n\u003cli\u003eKoteff J, Borland J, Chen S, Song I, Peppercorn A, Koshiba T, et al. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. Br J Clin Pharmacol 2013;75:990 \u0026ndash; 6. https://doi.org/10.1111/j.1365-2125.2012.04440.x.\u003c/li\u003e\n\u003cli\u003eMills A, Arribas JR, Andrade-Villanueva J, DiPerri G, Van Lunzen J, Koenig E, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis 2016;16:43 \u0026ndash; 52. https://doi.org/10.1016/s1473-3099(15)00348-5.\u003c/li\u003e\n\u003cli\u003eRaffi F, Orkin C, Clarke A, Slama L, Gallant J, Daar E, et al. Brief report: Long-term (96-week) efficacy and safety after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in HIV-infected, virologically suppressed adults. J Acquir Immune Defic Syndr 2017;75:226 \u0026ndash; 31. https://doi.org/10.1097/qai.0000000000001344.\u003c/li\u003e\n\u003cli\u003eUS Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents with HIV. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new-guidelines. [Accessed 22 June 2022].\u003c/li\u003e\n\u003cli\u003eFontecha M, Monsalvo M, Rodriguez-Sagrado MA, Vivancos MJ, Moreno A, Casado JL. Long-term improvement in renal, bone, lipid parameters, and CD4/CD8 ratio in HIV-infected patients switching to a dual therapy with lamivudine plus boosted darunavir. Infect Dis (Lond) 2019;51:293 \u0026ndash; 8. https://doi.org/10.1080/23744235.2018.1554908.\u003c/li\u003e\n\u003cli\u003eJabłonowska E, Pulik P, Kalinowska A, Gąsiorowski J, Parczewski M, Bociąga-Jasik M, et al. Efficacy and safety of nucleoside-sparing regimen based on raltegravir and ritonavir-boosted darunavir in HIV-1-infected treatment-experienced patients. J Med Virol 2017;89:2122 \u0026ndash; 9. https://doi.org/10.1002/jmv.24826.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"antiretroviral therapy, long-acting antiretroviral therapy, adherence, cabotegravir, rilpivirine, Japanese","lastPublishedDoi":"10.21203/rs.3.rs-3971672/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3971672/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAntiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB\u0026thinsp;+\u0026thinsp;RPV).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective cohort study included PLWH aged 18 years and older who switched to CAB\u0026thinsp;+\u0026thinsp;RPV between June 2022 and May 2023. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 48 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was employed to estimate changes in clinical data from baseline.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThirty-eight male participants were enrolled. Viral suppression was maintained and no cases of virological failure were observed (estimated value:-10.9, 95%CI: -37.5\u0026ndash;15.8]. Renal function improved (estimated value: -0.04, 95%CI: -0.07 \u0026ndash; -0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased significantly after switching to CAB\u0026thinsp;+\u0026thinsp;RPV(estimated value: 6.6, 95%CI: 2.2\u0026ndash;11.0).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLong-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being, but patient selection and monitoring to prevent HBV-related complications are important.\u003c/p\u003e\u003ch2\u003eEthics and dissemination:\u003c/h2\u003e \u003cp\u003e This study was conducted as a single-center study and was reviewed and approved by the Ethics Review Committee of Osaka City General Hospital (approval number: 2210072).\u003c/p\u003e","manuscriptTitle":"Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-06 19:26:48","doi":"10.21203/rs.3.rs-3971672/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2024-05-30T04:58:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"224087427245761835285331152634543978222","date":"2024-05-23T22:09:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-15T06:23:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"148623529795061320843053923547378354881","date":"2024-05-01T14:57:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7448d644-ef47-46d8-a93c-2505adc1bc9a","date":"2024-04-02T20:02:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-27T13:50:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-26T13:05:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-03-05T04:32:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-04T12:02:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-02-20T04:47:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ad9b104-def6-4cd9-8376-c43cdf6bb92c","owner":[],"postedDate":"March 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-23T17:29:10+00:00","versionOfRecord":{"articleIdentity":"rs-3971672","link":"https://doi.org/10.1186/s12879-024-09904-x","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2024-09-16 15:56:50","publishedOnDateReadable":"September 16th, 2024"},"versionCreatedAt":"2024-03-06 19:26:48","video":"","vorDoi":"10.1186/s12879-024-09904-x","vorDoiUrl":"https://doi.org/10.1186/s12879-024-09904-x","workflowStages":[]},"version":"v1","identity":"rs-3971672","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3971672","identity":"rs-3971672","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}