Real-World Study of HIV Patients Starting Antiretroviral Treatment With Boosted Protease Inhibitors in the Integrase Inhibitors Era

Real-World Study of HIV Patients Starting Antiretroviral Treatment With Boosted Protease Inhibitors in the Integrase Inhibitors Era | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Real-World Study of HIV Patients Starting Antiretroviral Treatment With Boosted Protease Inhibitors in the Integrase Inhibitors Era Ana Arancón Pardo, Carmen Mateos Salillas, Inmaculada Jiménez-Nácher, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1836324/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Boosted-protease inhibitors (b-PIs) are not recommended for initial therapy in HIV patients, but there is still a cohort of patients who could benefit from this antiretroviral treatment (ART). The purpose of this study was to analyze the profile of HIV patients who receive for the first time an ART containing two nucleoside reverse transcriptase inhibitors (NRTIs) and one b-PI. Efficacy and safety of this treatment, as well as the reasons for starting and changing it, were evaluated. Methods An observational, retrospective study was performed on the use of b-PIs in adult HIV patients. Individuals who started treatment with two NRTIs (emtricitabine and tenofovir alafenamide) and one b-PI (darunavir combined with cobicistat or ritonavir) between October 2019 and September 2021 were eligible for our study. This study was retrospectively registered by local Ethics Committee of our hospital (protocol number: PI-5066) on January 13th 2022. Results Overall, 52 patients started ART with two NRTIs plus one b-PIs. Only 8% of them were naïve, 21% received already two NRTIs plus a b-PI and 71% received other regimens. Reasons to start PIs were adverse effects to previous treatment and previous treatment failure. Most patients continued PIs treatment during the 2 years follow-up period and only six of them withdrew it. Conclusions This study analyzes the subgroup of patients that could benefit from treatment with b-PIs in the current era of integrase inhibitors. Even though its use is minority, its efficacy is high especially in patients with toxicity, therapeutic failure or poor adherence to other ARTs. HIV/AIDS Antiretrovirals Protease inhibitors Clinical Practice Darunavir Figures Figure 1 Figure 2 Background Infection caused by human immunodeficiency virus (HIV) is responsible for the development of acquired human immunodeficiency syndrome (AIDS). With the introduction of highly active antiretroviral therapy (HAART) in 1996, people infected with HIV have managed to keep an undetectable viral load, increasing significantly their life expectancy 1 , 2 . Despite all, the selection of optimal antiretroviral treatment (ART) for each patient is still a challenge. Current guidelines recommend integrase strand transfer inhibitors (INSTIs) as the initial therapy for HIV treatment-naïve patients because of its high potency and few adverse effects. Therefore, nowadays first-line therapy of HIV infection are regimens based on three drugs, usually the combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one INSTI 3 , 4 . In this way, regimens that previously were considered priority schemes are now used when patients do not respond to INSTIs or when toxicity appears. Regarding safety, despite INSTIs have a positive toxicity profile, some adverse events have been reported with their use, such as neuropsychiatric events and metabolic issues 5 , 6 . Because of that, some patients’ optimal ART are not INSTIs and clinicians are required to choose another regimen. Alternative regimens for HIV patients include the combination of two NRTIs plus a protease inhibitor (PI). Even though initial PIs had many side effects, recent generations are well tolerated, have a convenient dosage, high potency and increased barrier to resistance. Co-administration of PIs with a pharmacokinetic enhancer has greatly contributed to their effective and safe therapeutic profile, although significant drug-drug interactions can appear due to its potent inhibitory effect on cytochrome CYP 450 7 . Darunavir (DRV) is one of the new generation PIs, frequently recommended by international guidelines because it has superior efficacy on wild-type HIV but also on already resistant strains. DRV boosted with ritonavir (r) or cobicistat (c) is an ART available for both naïve and treatment-experienced patients 3 , 4 . Nevertheless a superior safety profile of these combinations over INSTIs has yet to be demonstrated 8 . Therefore, in current era of integrase inhibitors, there is still a subgroup of patients that could benefit from treatment with boosted-protease inhibitors (b-PIs). This study aimed to assess the profile of HIV patients who receive for the first time an ART containing two NRTIs and one b-PI. Methods Study design This was an observational, retrospective study focused on patients starting a PI-based therapy conducted in a tertiary hospital in Spain. The data collection period was from October 2019 to September 2021. Study population We collected clinical datasets of patients with HIV who started in our hospital an ART with two NRTIs and one b-PI. Nowadays only two PI-based regimens are recommended in our hospital because of its better safety profile compared with other PIs: DRV/c/emtricitabine (FTC)/tenofovir alafenamide (TAF) in single tablet regimen (STR) and DRV/r + FTC/TAF. Patients who started treatment with those two ART were included in our study. Study objectives The main objective of this study was to analyze the profile of HIV patients to whom we dispensed for the first time an ART containing two NRTIs and a b-PI from the Hospital Pharmacy. Secondary objectives were to assess the efficacy and safety of this treatment, as well as the reasons for starting and changing this ART. Data sources and statistical analysis Clinical records of all evaluated patients were reviewed to collect information concerning demographic characteristics (age and sex), patients’ clinical characteristics (HIV stage, HIV viral load and CD4 + cell count at the beginning of treatment), and treatment characteristics (previous ART, reasons for initiation, duration of treatment, discontinuation of treatment, reasons for discontinuation and treatment switched to). Reasons to start a b-PI treatment were classified into the following categories: toxicity to previous ART, treatment failure, poor adhesion, intensifying treatment and monitoring recovery. Reasons to discontinue b-PI treatment were classified into toxicity and treatment failure. Electronic medical records of our hospital (HCIS®) was used to collect all data. In pharmaceutical care consultation, patients were followed using the Farmatools Dominion® programme device Dispensación a Pacientes Externos (Outpatient dispensing). Results Data were collected on a total of 353 HIV patients that started a tracking in our hospital within the study period. Fifty-two patients (14,7%) started an ART with FTC/TAF in combination with DRV/r or DRV/c. Among those patients, most of them were male and the median age was 48 years. We included patients from all HIV stages. Table 1 includes patients’ clinical and demographic characteristics. Table 1 Demographic and clinical characteristics of patients included in the study. Age (years), median [range] 48 [39–56] Sex, n (%) Male 42 (80,8) Female 10 (19,2) HIV stage, % A1 11,5 A2 13,5 A3 9,6 B1 0 B2 5,8 B3 11,5 C1 1,9 C2 1,9 C3 23,1 No data 21,2 Baseline CD4 cell count (cells/mm 3 ), median [range] 538 [254–793] Baseline viral load (copies/mL), median [range] 126 [0-8050] The ART received by patients before starting the regimen based on 2 NRTIs + 1 b-PI in our hospital is shown in Fig. 1 . Among the fifty-two patients, 4 were naïve (8%) and 11 patients (21%) were already treated with a regime of 2 NRTIs + b-PI but in another hospital or with the drugs administered in multi-tablet regimen (MTR). The remaining 37 patients (71%) were previously treated with a wide variety of other regimes different from 2 NRTIs + b-PI. The most frequent combination of prior antiretroviral drugs were two NRTIs plus an INSTI. Analyzing the reasons why the 37 patients switched from a prior ART to a PI-based regimen, we observed that most of them modified their treatment due to toxicity to previous treatments (43%) and secondly because of treatment failure (30%). Detailed information about reasons to start the PI-based regimen is included in Fig. 2 . Detailed information about the types of adverse effects to previous treatment is included in Table 2 . Table 2 Side effects leading to change to a regimen based on b-PIs. Adverse effect Number of patients Frequency Neurological (mainly sleeping disorders) 14 88% Gastrointestinal 1 6% Metabolic 1 6% During the 96 weeks of follow-up, the median duration of treatment with b-PIs was 15.5 months (IQR 5.0-21.8 months). Six patients (11.5%) discontinued treatment during the follow-up, five of them (83.3%) due to the appearance of adverse effects and one (16.7%) due to treatment failure. Central nervous system toxicity was the most frequent (anxiety, insomnia and tiredness). Only one of the patients who discontinued was naïve and the cause of discontinuation was hypercholesterolemia. The therapy used after withdrawal of this treatment was: in 3/6 patients two NRTIs plus an INSTI, in 2/6 patients one NRTI plus an INSTI and in 1/6 two NRTIs plus another PI. Discussion Drugs commercialization is based on clinical trials, which are developed with that molecule in a population with specific characteristics. However, it is important to develop real-world evidence (RWE) studies because their results can improve patient care by complementing information obtained from traditional clinical trial programs 9 . Nowadays, there is a large number of drugs available for treatment of HIV patients. Current guidelines recommend as first line the use of two NRTIs plus an INSTI, relegating the use of protease inhibitors as alternative therapies 3 , 4 , 10 . Our results are consistent with these recommendations, as most patients had prior treatment consisting of the mentioned triple therapy. In addition, only four patients were naïve, reflecting that this treatment is not used as first choice. This suggests the need to analyze which subgroup of patients may benefit from treatment with PIs in real-world. Focusing on the reasons to start PIs, the main cause was adverse effects to previous treatment (43% of patients included in our study), mainly CNS and gastrointestinal toxicity caused by INSTIs. These results are in line with those of several other studies which reported that INSTIs are related with sleeping orders and weight gain, although they are recommended as first-choice because of their safety profile 5 , 6 , 11 , 12 . The second reason for switching to a regimen based on PIs was previous treatment failure, shown in the appearance of detectable HIV plasma RNA or resistance development. In this scenario, b-PIs are the drugs that have been shown to have the highest barrier to resistance and among them, DRV is the most recommended due to its pharmacokinetics 13 , 14 . Moreover, our results showed that patients with poor adherence or who had lost medical follow-up could benefit from PIs treatment because of its high genetic barrier. In fact, up to 23.1% of our patients had less than 200 CD4 cells/mm 3 and AIDS signs (C3 HIV stage). As Chow et al. highlighted in their review, patients using STR have higher persistence and adherence to the treatment compared to those using MTR 15 . This explains why PIs were displaced by others ART when they started to be commercialized in STR. Nevertheless, with the availability of STR PIs, a new scenario is presented. Furthermore, these recent generations of PIs co-administrated with a pharmacokinetic enhancer are better tolerated than the previous ones and have a higher potency 7 . This was evidenced in our study because most patients continued the treatment during the 2 years of follow-up period, and only six of them withdrew it. Among these patients, only one stopped the treatment due to treatment failure. The current study was performed in a tertiary hospital which attends 3500 HIV patients. This represents 16% of HIV patients in the Community of Madrid, Spain 16 . This fact gives strength to our results and thus could be extrapolated to a larger cohort of patients. This study is subject of certain limitations. First, it had a retrospective and single-center design. Therefore, prospective multicenter studies are necessary to elucidate the trends in outcomes of patients treated with PIs. Second, we included patients treated with PIs both as STR and as MTR. Since PIs in STR were commercialized during the follow-up period of this study, it is possible that there was a change in the prescribing trends for these drugs. Conclusions Although the use of ART based on 2 NRTIs and a PI is minority, its efficacy is high. This regimen may be especially useful in patients with toxicity, therapeutic failure or poor adherence to other antiretrovirals. Declarations Ethics approval and consent to participate This study was conducted in compliance with Human Subjects Research Committee requirements and was approved by local Ethics Committee of our hospital (Comité de ética de la investigación con medicamentos del Hospital Universitario La Paz) on January 13 th 2022. Protocol number is PI-5066. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding None declared. Authors' contributions AAP and IJN were involved in design. AAP and CMS performed data collection. AAP, CMS and IJN wrote the manuscript. All authors read and approved the article. Acknowledgements The authors would like to thank all members of the Pharmacy Department, especially those who are part of the research group “ResInvest”, as well as the Infectious Diseases Unit for their support during the development of this study. References Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. The Lancet. 2008 Jul;372(9635):293–9. doi: 10.1016/S0140-6736(08)61113-7 . Samji H, Cescon A, Hogg RS, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One. 2013;8(12):e81355. doi: 10.1371/journal.pone.0081355 . Clinical Info HIV. Available from: https://clinicalinfo.hiv.gov/es/guidelines . Accessed 2021 Dec 16. Martínez E, Arribas JR, Polo R, et al. GeSIDA guidelines. 2022:146. Ando N, Nishijima T, Mizushima D, et al. Long-term weight gain after initiating combination antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus. Int J Infect Dis. 2021 Sep;110:21–8. doi: 10.1016/j.ijid.2021.07.030 . Buzón-Martín L. Weight gain in HIV-infected individuals using distinct antiretroviral drugs. AIDS Rev. 2020;22(3):158–67. doi: 10.24875/AIDSRev.M20000036 . Marin RC, Behl T, Negrut N, Bungau S. Management of Antiretroviral Therapy with Boosted Protease Inhibitors-Darunavir/Ritonavir or Darunavir/Cobicistat. Biomedicines. 2021 Mar 18;9(3):313. doi: 10.3390/biomedicines9030313 . Ciccullo A, Baldin G, Putaggio C, Di Giambenedetto S, Borghetti A. Comparative safety review of recommended, first-line single-tablet regimens in patients with HIV. Expert Opin Drug Saf. 2021 Nov;20(11):1317–32. doi: 10.1080/14740338.2021.1931115 . Naidoo P, Bouharati C, Rambiritch V, et al. Real-world evidence and product development: Opportunities, challenges and risk mitigation. Wien Klin Wochenschr. 2021 Aug;133(15–16):840–6. doi: 10.1007/s00508-021-01851-w . Integrase Inhibitors: After 10 Years of Experience, Is the Best Yet to Come? - Brooks – 2019 - Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Wiley Online Library. Available from: https://accpjournals-onlinelibrary-wiley-com.m-ulp.a 17.csinet.es/doi/10.1002/phar.2246 . Accessed 2022 Feb 14. Ruderman SA, Crane HM, Nance RM, et al. Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era. J Acquir Immune Defic Syndr. 2021 Mar 1;86(3):339–43. doi: 10.1097/QAI.0000000000002556 . Hoffmann C, Llibre JM. Neuropsychiatric Adverse Events with Dolutegravir and Other Integrase Strand Transfer Inhibitors. AIDSRev. 2019 Jul 26;21(1):1768. doi: 10.24875/AIDSRev.19000023 . Madruga JV, Berger D, McMurchie M, et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet. 2007 Jul 7;370(9581):49–58. doi: 10.1016/S0140-6736(07)61049-6 . Sension M, Cahn P, Domingo P, et al. Subgroup analysis of virological response rates with once- and twice-daily darunavir/ritonavir in treatment-experienced patients without darunavir resistance-associated mutations in the ODIN trial. HIV Med. 2013 Aug;14(7):437–44. doi: 10.1111/hiv.12024 . Chow W, Donga P, Côté-Sergent A, et al. Treatment Patterns and Predictors of Adherence in HIV Patients Receiving Single- or Multiple-Tablet Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide. PPA. 2020 Nov 23;14:2315–26. doi: 10.2147/PPA.S272211 . VIH (Virus de la Inmunodeficiencia Humana) and ITS (Infecciones de Transmisión Sexual). Community of Madrid. 2017. Available from: https://www.comunidad.madrid/servicios/salud/vih-virus-inmunodeficiencia-humana-its-infecciones-transmision-sexual . Accessed 2022 Feb 28. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-1836324","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":119635296,"identity":"11182d4e-6d02-4a12-a956-117b45aedec8","order_by":0,"name":"Ana Arancón Pardo","email":"data:image/png;base64,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","orcid":"","institution":"La Paz University Hospital-IdiPAZ","correspondingAuthor":true,"prefix":"","firstName":"Ana","middleName":"Arancón","lastName":"Pardo","suffix":""},{"id":119635300,"identity":"78b9a6cc-1dee-481c-b83f-8eac9536a392","order_by":1,"name":"Carmen Mateos Salillas","email":"","orcid":"","institution":"La Paz University Hospital-IdiPAZ","correspondingAuthor":false,"prefix":"","firstName":"Carmen","middleName":"Mateos","lastName":"Salillas","suffix":""},{"id":119635303,"identity":"bcca76cd-66f7-4ac6-bb1e-a57804d33d13","order_by":2,"name":"Inmaculada Jiménez-Nácher","email":"","orcid":"","institution":"La Paz University Hospital-IdiPAZ","correspondingAuthor":false,"prefix":"","firstName":"Inmaculada","middleName":"","lastName":"Jiménez-Nácher","suffix":""},{"id":119635304,"identity":"6e78eee7-3cdb-41a4-bd81-331290e5e722","order_by":3,"name":"Juan González García","email":"","orcid":"","institution":"La Paz University Hospital-IdiPAZ","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"González","lastName":"García","suffix":""},{"id":119635305,"identity":"a7aa708b-3d26-4e1c-a884-f45995bef6c5","order_by":4,"name":"Alicia Herrero Ambrosio","email":"","orcid":"","institution":"La Paz University Hospital-IdiPAZ","correspondingAuthor":false,"prefix":"","firstName":"Alicia","middleName":"Herrero","lastName":"Ambrosio","suffix":""}],"badges":[],"createdAt":"2022-07-07 17:29:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1836324/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1836324/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":23778566,"identity":"cff74dc0-28e7-4d8a-85cc-f354d74f2358","added_by":"auto","created_at":"2022-07-12 17:30:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":95782,"visible":true,"origin":"","legend":"\u003cp\u003ePrevious ARTs of patients who started a regimen based on b-PIs. NRTI, nucleoside reverse transcriptase inhibitor; INSTI, integrase strand transfer inhibitors; b-PI, boosted-protease inhibitor; ART, antiretroviral treatment; NNRTI, non-nucleoside reverse transcriptase inhibitor.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1836324/v1/0c97323338d2b4022f32c635.png"},{"id":23778567,"identity":"be945c8f-89ee-461c-8b44-85bd92132054","added_by":"auto","created_at":"2022-07-12 17:30:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21535,"visible":true,"origin":"","legend":"\u003cp\u003eReasons to start a regimen based on b-PIs.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1836324/v1/8ca89fb011476df39b3635ff.png"},{"id":24599591,"identity":"41f9b346-d4b6-4070-9532-4805471f4ae7","added_by":"auto","created_at":"2022-08-01 14:59:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":390719,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1836324/v1/0541414c-b19b-4427-9c24-b9e2b2683d9a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eReal-World Study of HIV Patients Starting Antiretroviral Treatment With Boosted Protease Inhibitors in the Integrase Inhibitors Era\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eInfection caused by human immunodeficiency virus (HIV) is responsible for the development of acquired human immunodeficiency syndrome (AIDS). With the introduction of highly active antiretroviral therapy (HAART) in 1996, people infected with HIV have managed to keep an undetectable viral load, increasing significantly their life expectancy\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Despite all, the selection of optimal antiretroviral treatment (ART) for each patient is still a challenge.\u003c/p\u003e \u003cp\u003e Current guidelines recommend integrase strand transfer inhibitors (INSTIs) as the initial therapy for HIV treatment-na\u0026iuml;ve patients because of its high potency and few adverse effects. Therefore, nowadays first-line therapy of HIV infection are regimens based on three drugs, usually the combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one INSTI\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this way, regimens that previously were considered priority schemes are now used when patients do not respond to INSTIs or when toxicity appears. Regarding safety, despite INSTIs have a positive toxicity profile, some adverse events have been reported with their use, such as neuropsychiatric events and metabolic issues\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Because of that, some patients\u0026rsquo; optimal ART are not INSTIs and clinicians are required to choose another regimen.\u003c/p\u003e \u003cp\u003eAlternative regimens for HIV patients include the combination of two NRTIs plus a protease inhibitor (PI). Even though initial PIs had many side effects, recent generations are well tolerated, have a convenient dosage, high potency and increased barrier to resistance. Co-administration of PIs with a pharmacokinetic enhancer has greatly contributed to their effective and safe therapeutic profile, although significant drug-drug interactions can appear due to its potent inhibitory effect on cytochrome CYP 450\u003csup\u003e7\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e Darunavir (DRV) is one of the new generation PIs, frequently recommended by international guidelines because it has superior efficacy on wild-type HIV but also on already resistant strains. DRV boosted with ritonavir (r) or cobicistat (c) is an ART available for both na\u0026iuml;ve and treatment-experienced patients\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Nevertheless a superior safety profile of these combinations over INSTIs has yet to be demonstrated\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTherefore, in current era of integrase inhibitors, there is still a subgroup of patients that could benefit from treatment with boosted-protease inhibitors (b-PIs). This study aimed to assess the profile of HIV patients who receive for the first time an ART containing two NRTIs and one b-PI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis was an observational, retrospective study focused on patients starting a PI-based therapy conducted in a tertiary hospital in Spain. The data collection period was from October 2019 to September 2021.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eWe collected clinical datasets of patients with HIV who started in our hospital an ART with two NRTIs and one b-PI. Nowadays only two PI-based regimens are recommended in our hospital because of its better safety profile compared with other PIs: DRV/c/emtricitabine (FTC)/tenofovir alafenamide (TAF) in single tablet regimen (STR) and DRV/r\u0026thinsp;+\u0026thinsp;FTC/TAF. Patients who started treatment with those two ART were included in our study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy objectives\u003c/h2\u003e \u003cp\u003eThe main objective of this study was to analyze the profile of HIV patients to whom we dispensed for the first time an ART containing two NRTIs and a b-PI from the Hospital Pharmacy. Secondary objectives were to assess the efficacy and safety of this treatment, as well as the reasons for starting and changing this ART.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData sources and statistical analysis\u003c/h2\u003e \u003cp\u003eClinical records of all evaluated patients were reviewed to collect information concerning demographic characteristics (age and sex), patients\u0026rsquo; clinical characteristics (HIV stage, HIV viral load and CD4\u0026thinsp;+\u0026thinsp;cell count at the beginning of treatment), and treatment characteristics (previous ART, reasons for initiation, duration of treatment, discontinuation of treatment, reasons for discontinuation and treatment switched to). Reasons to start a b-PI treatment were classified into the following categories: toxicity to previous ART, treatment failure, poor adhesion, intensifying treatment and monitoring recovery. Reasons to discontinue b-PI treatment were classified into toxicity and treatment failure.\u003c/p\u003e \u003cp\u003eElectronic medical records of our hospital (HCIS\u0026reg;) was used to collect all data. In pharmaceutical care consultation, patients were followed using the Farmatools Dominion\u0026reg; programme device Dispensaci\u0026oacute;n a Pacientes Externos (Outpatient dispensing).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eData were collected on a total of 353 HIV patients that started a tracking in our hospital within the study period. Fifty-two patients (14,7%) started an ART with FTC/TAF in combination with DRV/r or DRV/c.\u003c/p\u003e \u003cp\u003eAmong those patients, most of them were male and the median age was 48 years. We included patients from all HIV stages. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e includes patients\u0026rsquo; clinical and demographic characteristics.\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\u003eDemographic and clinical characteristics of patients included in the study.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), median [range]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e48 [39\u0026ndash;56]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (80,8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (19,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003eHIV stage, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13,5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9,6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23,1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21,2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline CD4 cell count (cells/mm\u003csup\u003e3\u003c/sup\u003e), median [range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e538 [254\u0026ndash;793]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline viral load (copies/mL), median [range]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e126 [0-8050]\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\u003eThe ART received by patients before starting the regimen based on 2 NRTIs\u0026thinsp;+\u0026thinsp;1 b-PI in our hospital is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among the fifty-two patients, 4 were na\u0026iuml;ve (8%) and 11 patients (21%) were already treated with a regime of 2 NRTIs\u0026thinsp;+\u0026thinsp;b-PI but in another hospital or with the drugs administered in multi-tablet regimen (MTR). The remaining 37 patients (71%) were previously treated with a wide variety of other regimes different from 2 NRTIs\u0026thinsp;+\u0026thinsp;b-PI. The most frequent combination of prior antiretroviral drugs were two NRTIs plus an INSTI.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAnalyzing the reasons why the 37 patients switched from a prior ART to a PI-based regimen, we observed that most of them modified their treatment due to toxicity to previous treatments (43%) and secondly because of treatment failure (30%). Detailed information about reasons to start the PI-based regimen is included in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Detailed information about the types of adverse effects to previous treatment is included in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSide effects leading to change to a regimen based on b-PIs.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse effect\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurological\u003c/p\u003e \u003cp\u003e(mainly sleeping disorders)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetabolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6%\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\u003eDuring the 96 weeks of follow-up, the median duration of treatment with b-PIs was 15.5 months (IQR 5.0-21.8 months). Six patients (11.5%) discontinued treatment during the follow-up, five of them (83.3%) due to the appearance of adverse effects and one (16.7%) due to treatment failure. Central nervous system toxicity was the most frequent (anxiety, insomnia and tiredness). Only one of the patients who discontinued was na\u0026iuml;ve and the cause of discontinuation was hypercholesterolemia.\u003c/p\u003e \u003cp\u003eThe therapy used after withdrawal of this treatment was: in 3/6 patients two NRTIs plus an INSTI, in 2/6 patients one NRTI plus an INSTI and in 1/6 two NRTIs plus another PI.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDrugs commercialization is based on clinical trials, which are developed with that molecule in a population with specific characteristics. However, it is important to develop real-world evidence (RWE) studies because their results can improve patient care by complementing information obtained from traditional clinical trial programs\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNowadays, there is a large number of drugs available for treatment of HIV patients. Current guidelines recommend as first line the use of two NRTIs plus an INSTI, relegating the use of protease inhibitors as alternative therapies\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Our results are consistent with these recommendations, as most patients had prior treatment consisting of the mentioned triple therapy. In addition, only four patients were na\u0026iuml;ve, reflecting that this treatment is not used as first choice. This suggests the need to analyze which subgroup of patients may benefit from treatment with PIs in real-world.\u003c/p\u003e \u003cp\u003eFocusing on the reasons to start PIs, the main cause was adverse effects to previous treatment (43% of patients included in our study), mainly CNS and gastrointestinal toxicity caused by INSTIs. These results are in line with those of several other studies which reported that INSTIs are related with sleeping orders and weight gain, although they are recommended as first-choice because of their safety profile\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe second reason for switching to a regimen based on PIs was previous treatment failure, shown in the appearance of detectable HIV plasma RNA or resistance development. In this scenario, b-PIs are the drugs that have been shown to have the highest barrier to resistance and among them, DRV is the most recommended due to its pharmacokinetics\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, our results showed that patients with poor adherence or who had lost medical follow-up could benefit from PIs treatment because of its high genetic barrier. In fact, up to 23.1% of our patients had less than 200 CD4 cells/mm\u003csup\u003e3\u003c/sup\u003e and AIDS signs (C3 HIV stage).\u003c/p\u003e \u003cp\u003eAs Chow et al. highlighted in their review, patients using STR have higher persistence and adherence to the treatment compared to those using MTR\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. This explains why PIs were displaced by others ART when they started to be commercialized in STR. Nevertheless, with the availability of STR PIs, a new scenario is presented.\u003c/p\u003e \u003cp\u003eFurthermore, these recent generations of PIs co-administrated with a pharmacokinetic enhancer are better tolerated than the previous ones and have a higher potency\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. This was evidenced in our study because most patients continued the treatment during the 2 years of follow-up period, and only six of them withdrew it. Among these patients, only one stopped the treatment due to treatment failure.\u003c/p\u003e \u003cp\u003eThe current study was performed in a tertiary hospital which attends 3500 HIV patients. This represents 16% of HIV patients in the Community of Madrid, Spain\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. This fact gives strength to our results and thus could be extrapolated to a larger cohort of patients.\u003c/p\u003e \u003cp\u003eThis study is subject of certain limitations. First, it had a retrospective and single-center design. Therefore, prospective multicenter studies are necessary to elucidate the trends in outcomes of patients treated with PIs. Second, we included patients treated with PIs both as STR and as MTR. Since PIs in STR were commercialized during the follow-up period of this study, it is possible that there was a change in the prescribing trends for these drugs.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAlthough the use of ART based on 2 NRTIs and a PI is minority, its efficacy is high. This regimen may be especially useful in patients with toxicity, therapeutic failure or poor adherence to other antiretrovirals.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in compliance with Human Subjects Research Committee requirements and was approved by local Ethics Committee of our hospital (Comit\u0026eacute; de \u0026eacute;tica de la investigaci\u0026oacute;n con medicamentos del Hospital Universitario La Paz) on January 13\u003csup\u003eth\u003c/sup\u003e 2022. Protocol number is PI-5066.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\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\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAAP and IJN were involved in design. AAP and CMS performed data collection. AAP, CMS and IJN wrote the manuscript. All authors read and approved the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all members of the Pharmacy Department, especially those who are part of the research group \u0026ldquo;ResInvest\u0026rdquo;, as well as the Infectious Diseases Unit for their support during the development of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAntiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. The Lancet. 2008 Jul;372(9635):293\u0026ndash;9. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(08)61113-7\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(08)61113-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamji H, Cescon A, Hogg RS, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One. 2013;8(12):e81355. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0081355\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0081355\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClinical Info HIV. 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Accessed 2022 Feb 28.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"HIV/AIDS, Antiretrovirals, Protease inhibitors, Clinical Practice, Darunavir","lastPublishedDoi":"10.21203/rs.3.rs-1836324/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1836324/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBoosted-protease inhibitors (b-PIs) are not recommended for initial therapy in HIV patients, but there is still a cohort of patients who could benefit from this antiretroviral treatment (ART). The purpose of this study was to analyze the profile of HIV patients who receive for the first time an ART containing two nucleoside reverse transcriptase inhibitors (NRTIs) and one b-PI. Efficacy and safety of this treatment, as well as the reasons for starting and changing it, were evaluated.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAn observational, retrospective study was performed on the use of b-PIs in adult HIV patients. Individuals who started treatment with two NRTIs (emtricitabine and tenofovir alafenamide) and one b-PI (darunavir combined with cobicistat or ritonavir) between October 2019 and September 2021 were eligible for our study. This study was retrospectively registered by local Ethics Committee of our hospital (protocol number: PI-5066) on January 13th 2022.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOverall, 52 patients started ART with two NRTIs plus one b-PIs. Only 8% of them were na\u0026iuml;ve, 21% received already two NRTIs plus a b-PI and 71% received other regimens. Reasons to start PIs were adverse effects to previous treatment and previous treatment failure. Most patients continued PIs treatment during the 2 years follow-up period and only six of them withdrew it.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study analyzes the subgroup of patients that could benefit from treatment with b-PIs in the current era of integrase inhibitors. Even though its use is minority, its efficacy is high especially in patients with toxicity, therapeutic failure or poor adherence to other ARTs.\u003c/p\u003e","manuscriptTitle":"Real-World Study of HIV Patients Starting Antiretroviral Treatment With Boosted Protease Inhibitors in the Integrase Inhibitors Era","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-12 17:30:21","doi":"10.21203/rs.3.rs-1836324/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0af1779a-6750-4657-a715-4ddd066195cf","owner":[],"postedDate":"July 12th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-08-01T14:59:23+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-12 17:30:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1836324","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1836324","identity":"rs-1836324","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}