Kidney Dysfunction In Young People Living With HIV On Dolutegravir-Based Regimens In Kampala, Uganda

Kidney Dysfunction In Young People Living With HIV On Dolutegravir-Based Regimens In Kampala, Uganda | 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 Kidney Dysfunction In Young People Living With HIV On Dolutegravir-Based Regimens In Kampala, Uganda Esther M Nasuuna, Risa Hoffman, Robert Kalyesubula, Chido Dziva Chikwari, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9091584/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract We assessed the association between dolutegravir (DTG)-based antiretroviral therapy and kidney abnormalities among young people living with HIV aged 10–24 years in Kampala, Uganda. In this cross-sectional study, albumin–creatinine ratio (ACR), proteinuria, and estimated glomerular filtration rate (eGFR) were measured. Among 483 participants, 78% received tenofovir (TDF)/DTG. Mean serum creatinine was higher and creatinine-based eGFR lower among those on TDF/DTG, while cystatin C and cystatin C–based eGFR were similar. The prevalence of elevated ACR, proteinuria, and eGFR <90 ml/min/1.73m² was similar. Kidney abnormalities were common, supporting the need for longitudinal studies to clarify chronic kidney disease risk . Kidney function dolutegravir young people living with HIV Sub Saharan Africa Introduction Antiretroviral therapy (ART) has transformed HIV infection from a fatal illness into a chronic condition [ 1 ]. The success of ART means that young people living with HIV (YPLHIV) are increasingly surviving into adulthood and face long-term health challenges [ 1 ]. Non-communicable conditions, including chronic kidney disease, have emerged as important contributors to morbidity and mortality [ 2 ]. Multiple factors —direct effects of HIV, coexisting infections, traditional risk factors (hypertension and diabetes), and exposure to nephrotoxic ART— drive kidney dysfunction in YPLHIV [ 3 ]. Young people are especially vulnerable because they are likely to be exposed to ART for many decades, during which cumulative drug effects and ongoing HIV-related immune activation may increase the risk of kidney dysfunction [ 4 ]. The recent global transition to dolutegravir (DTG)-based regimens has introduced new complexities in monitoring kidney function. DTG is now the preferred first-line ART in many low- and middle-income countries, including Uganda, because of its high efficacy and favourable tolerability profile [ 5 ]. However, DTG inhibits tubular secretion of creatinine without affecting glomerular filtration, leading to modest but persistent increases in serum creatinine [ 6 ]. This pharmacological effect may confound the assessment of kidney function and obscure early signs of true kidney impairment. There is a critical need to characterise the burden of kidney dysfunction in YPLHIV on DTG-based ART in Uganda. We set out to describe the prevalence and association of kidney dysfunction with DTG-based regimens among YPLHIV in Uganda. Methods We conducted a cross-sectional study in seven urban public health facilities in Kampala, Uganda, which provide comprehensive HIV care and treatment services, mostly for the urban poor. The study included YPLHIV aged 10–24 years with presumed perinatal HIV infection. Pregnant YPLHIV were excluded. Systematic random sampling (listing all YPLHIV in the clinics and picking out every other name) was used to identify potential participants. These were invited to join the study. Details of the parent study have been published previously [ 7 ]. Eligible participants were invited to the HIV clinic through a phone call to those above 18 years or the caregiver for those below 18 years. They were screened, consented, and enrolled. We collected urine samples for the albumin creatinine ratio (ACR), proteinuria on dipstick, and blood samples for serum creatinine and cystatin C. We estimated glomerular filtration rate (eGFR) using the CKDEPI 2021 equation or the Bedside Schwartz (< 18 years). Participants were interviewed to collect socio-demographic data such as age, sex, and socioeconomic status. Measurements were taken for weight, height, mid-upper arm circumference (MUAC), body mass index (BMI) was calculated as weight over height squared. Stunting was calculated according to the WHO standards [ 8 ]. Muscle mass was determined using a bioimpedance machine and calculated using sex and age-specific cut-offs. Data management and statistical analysis Data were collected in REDCap and analysed with STATA statistical software Version 18 (STATA Corp USA). Demographic and clinical data were summarised in percentages or means (standard deviation [SD]) and median (interquartile range [IQR]). We used chi-square tests to compare kidney function parameters of participants on tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and DTG compared with those on DTG combined with other Nucleoside Reverse Transcriptase Inhibitors, such as zidovudine or abacavir, and 3TC (other DTG regimens). Ethical considerations Ethical approval was received from the Uganda Virus Research Institute (UVRI) Research Ethics Committee (reference number GC/127/946), the Uganda National Council of Science and Technology (HS2578ES) and the London School of Hygiene and Tropical Medicine institutional review board (28797). All participants aged 18 years or older provided written informed consent. Those aged < 18 years, provided written participant assent, and caregiver consent. All participants with suspected CKD were referred to a nephrologist for management. Results Out of 500 YPLHIV, 483 were enrolled into the study, with 367 (76%) on TDF/3TC/DTG and 116 (24%) on other regimens. There were slightly more females than males in both groups. There were more underweight participants on the non-TDF-containing DTG regimens. Viral suppression, mean duration on ART, and muscle mass were similar in both groups. Table 1 Table 1 Demographic and clinical characteristics of the participants by ART regimen Mean Age in years (SD) TDF/DTG N = 367 Other/DTG N = 116 p-value 17.0 (3.5) 14.4 (3.4) < 0.001 10 to 17 231 (62.9%) 93 (80.2%) < 0.001 18 to 24 136 (37.1%) 23 (19.8%) Sex Female 211 (57.5%) 62 (53.4%) Socioeconomic status Lowest 129 (35.1%) 44 (37.9%) 0.86 Middle 114 (31.1%) 35 (30.2%) Highest 124 (33.8%) 37 (31.9%) Body mass index Normal 224 (61.2%) 44 (37.9%) < 0.001 Underweight 106 (29.0%) 67 (57.8%) Overweight 36 (9.8%) 5 (4.3%) Stunting Not stunted 221 (84.0%) 80 (79.2%) 0.28 Stunted 42 (16.0%) 21 (20.8%) Mid upper arm circumference (MUAC) Normal 338 (92.3%) 100 (86.2%) 0.05 Malnourished 28 ( 7.7%) 16 (13.8%) Weight (kg) 51.2 (11.5) 41.9 (12.7) < 0.001 Malnourished participants had a MUAC in either yellow or red. Participants' kidney parameters by regimen The mean serum creatinine levels were higher among participants on TDF/DTG compared to those on other DTG-based regimens without TDF, although the mean eGFR and the proportions with eGFR < 90 ml/min/1.73m 2 were similar. The mean cystatin C was similar in both groups. The mean eGFR was within normal limits and lower among those on TDF/DTG compared to those on other DTG-based regimens. Although the proportion with eGFRcystc below 90ml/min/1.73m 2 was higher among those on DTG-based regimens without TDF compared to those on TDF/DTG, this was not significant. The proportion of YPLHIV with ACR>30mg/g was higher among those on other DTG-based regimens, and proteinuria proportions were high but similar (Table 2 ). Table 2 Participant kidney parameters by ART regimen Variable TDF/DTG N = 367 Other DTG-based* N = 116 p-value Serum creatinine Mean (SD) 0.68 (0.15) 0.59 (0.14) 90ml/min 317 (87.3) 103 (89.6) 0.52 < 90ml/min 46 (12.7) 12 (10.4) Cystatin C Mean(SD) 0.81 (0.13) 0.81 (0.12) 0.78 eGFR cystatin C (SD) 114.2 (15.2) 116.5 (15.3) 0.15 eGFR cystatin C Above 90ml/min 212 (58.4) 60 (52.2) 0.47 Below 90ml/min 151 (41.6) 55 (47.8) Albumin creatinine ratio Below 30mg/g 328 (90.4) 100 (87.0) 0.29 Above 30mg/g 35 (9.6) 15 (13.0) Proteinuria Negative 263 (71.7) 81 (69.8) 0.70 Positive 104 (28.3) 35 (30.2) *Regimens with either abacavir or zidovudine together with lamivudine and dolutegravir. Discussion Our data suggest a high prevalence of kidney dysfunction (based on eGFR cystatin C below 90ml/min/1.73m 2 and proteinuria) among YPLHIV compared to youth who are not living with HIV, which is not associated with DTG/TDF versus other DTG-based regimens. Our findings are consistent with those of the ODYSSEY trial from Uganda, Thailand, Europe, Zimbabwe, and South Africa, which reported no kidney-related adverse effects in 707 children and adolescents living with HIV on DTG-based regimens coupled with NRTIs, including TDF at 96 weeks [ 9 ]. A systematic review on the efficacy and safety of DTG among children and adolescents reported data on 11 studies, which did not report any kidney-related adverse events, although the number of children on both DTG and TDF and the duration were not reported [ 10 ]. Taken together, these data are reassuring about ongoing use of DTG combined with TDF as first-line ART for YPLHIV initiating treatment in Uganda [ 5 ]. There are concerns about DTG obscuring kidney dysfunction, especially when it is co-administered with TDF, which is known to cause kidney dysfunction [ 11 , 12 ]. This concern has not yet been fully addressed, as there are very few studies done in Africa that involve young people living with HIV on both DTG and TDF [ 13 ]. A study done in Nigeria among 170 adult PLHIV found that those on TDF/DTG had impaired kidney function [ 14 ]. A pilot clinical trial showed that PLHIV who switched to TDF/DTG combination had a greater decline in eGFR compared to those switched to DTG/lamivudine [ 15 ]. A global systematic review and meta-analysis showed a 7% prevalence of chronic kidney disease among those treated with TDF, there was no mention of DTG effects [ 16 ]. Since the duration on ART is associated with risk of TDF kidney toxicity [ 17 ], and YPLHIV are exposed to TDF for a longer time than adults living with HIV, vigilant monitoring of kidney function is warranted for YPLHIV treated with TDF-containing regimens, to ensure early diagnosis. Use of tenofovir alafenamide (TAF) should also be considered, as this is associated with less kidney toxicity compared to TDF, according to data pooled from 26 clinical trials that also included children [ 18 ]. However, weight and metabolic changes should be monitored [ 19 ]. The main limitation of our study was the inability to compare the kidney function of YPLHIV on DTG based regimens to others who were not exposed to DTG, since most YPLHIV were switched to DTG following the WHO recommendations. We did not account for the regimen changes over time with the changing recommendations over the lifetime of the YPLHIV. It was also a cross-sectional study, and more information about long-term toxicity should be collected from longitudinal studies. The strengths are that the study was adequately powered to detect an association, and our findings are generalisable to YPLHIV living in settings similar to ours. Conclusion We found that YPLHIV on DTG-based regimens had a high prevalence of proteinuria and elevated ACR regardless of the nucleoside analogues utilized alongside DTG. However, eGFR calculated from both serum creatinine and cystatin C was largely within normal limits. Longer-term follow-up is needed to understand whether YPLHIV will develop chronic kidney disease as they age, and to elucidate risk factors for kidney disease progression, including safer long-term ART regimens. Abbreviations ACR Albumin Creatinine Ratio ART Anti-Retroviral Therapy BMI Body Mass Index CKD Chronic Kidney Disease CKD-EPI Chronic Kidney Disease Epidemiology Collaboration DTG Dolutegravir eGFR Estimated Glomerular Filtration Rate HIV Human Immunodeficiency Virus IQR Interquartile Range KDIGO Kidney Disease Improving Global Outcomes MUAC Mid upper arm circumference SD Standard Deviation SSA Sub-Saharan Africa USA United States of America WHO World Health Organization YPLHIV Young People Living with HIV Declarations Ethics approval and consent to participate The Uganda Virus Research Institute (UVRI) Research Ethics Committee (GC/127/946), the Uganda National Council of Science and Technology (HS2578ES), and the London School of Hygiene and Tropical Medicine (reference 28797) approved this study. All participants regardless of age provided informed consent/assent after provision of age-appropriate study information. Participants >18 years s provided a written informed consent. Children <18 years provided written assent, and their caregivers provided a written informed consent. The studies were conducted in accordance with the Declaration of Helsinki. Consent for publication : Not applicable Availability of data and materials To protect the confidentiality of the participants who provided the clinical data, the data that support the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding Support for the studies was provided by Fogarty International Centre, National Institutes of Health (grant #2D43TW009771-06) HIV and co-infections in Uganda. Esther Nasuuna, Doctoral Research Fellow, NIHR131273 is funded by the NIHR for this research project. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care. The funders had no role in the study design, collection, analysis or interpretation of data. Neither did they choose where this work gets published. Author contributions EN, RH, CD, HW contributed to the conceptualization and design of the study, data collection, analysis, interpretation, and editing the manuscript. EN, RH and HW drafted the manuscript. RK contributed to the interpretation of results and edited the manuscript for important scientific content. All authors reviewed and approved the manuscript before submission for publication. All authors are accountable for the work in this paper. Acknowledgments We wish to acknowledge the participants, their caregivers and the facility staff where this study took place. We also acknowledge the study team, Miss Evelyn Natuha, Miss Stella Mirembe and Mr. Malcolm Lwanga. We acknowledge the KCCA leadership and the PEPFAR program that supports HIV care for the YPLHIV. References Frigati, L.J., et al., Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy. The Lancet Child & Adolescent Health, 2020. 4 (9): p. 688-698. Frigati, L.J., et al., Multisystem impairment in South African adolescents with Perinatally acquired HIV on antiretroviral therapy (ART). Journal of the International AIDS Society, 2019. 22 (8): p. e25386. Swanepoel, C.R., et al., Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney international, 2018. 93 (3): p. 545-559. Bhimma, R., M.U. Purswani, and U. Kala, Kidney disease in children and adolescents with perinatal HIV‐1 infection. Journal of the International AIDS Society, 2013. 16 (1): p. 18596. world Health Organization, Updated recommendations in first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV . 2018, World Health Organisation: Netherlands. Cattaneo, D. and C. Gervasoni, Novel Antiretroviral Drugs in Patients with Renal Impairment: Clinical and Pharmacokinetic Considerations. European Journal of Drug Metabolism and Pharmacokinetics, 2017. 42 (4): p. 559-572. Nasuuna, E.M., et al., Comparison of the prevalence and associated factors of chronic kidney disease diagnosed by serum creatinine or cystatin C among young people living with HIV in Uganda. BMC nephrology, 2024. 25 (1): p. 422. WHO Multicentre Growth Reference Study Group, WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl, 2006. 450 : p. 76-85. Turkova, A., et al., Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. New England Journal of Medicine, 2021. 385 (27): p. 2531-2543. Townsend, C.L., et al., Effectiveness and safety of dolutegravir and raltegravir for treating children and adolescents living with HIV: a systematic review. Journal of the International AIDS Society, 2022. 25 (11): p. e25970. Kouamou, V., et al., Tenofovir, Lamivudine, and Dolutegravir Among Rural Adolescents in Zimbabwe: A Cautionary Tale. AIDS Research and Human Retroviruses, 2022. 38 (10): p. 774-778. Diack, A., et al., Progressive Decline of the Glomerular Filtration Rate in HIV-infected Children Treated With Tenofovir Disoproxil Fumarate-based Regimens in West and Central Africa. The Pediatric infectious disease journal, 2020. 39 (8): p. 737-739. Mtisi, T.J., et al., Tenofovir-associated kidney disease in Africans: a systematic review. AIDS research and therapy, 2019. 16 (1): p. 12. Odegbemi, O.B., et al., Renal Function and Nephrotoxicity Assessment in People Living with HIV on Tenofovir, Lamivudine, and Dolutegravir Therapy: A Cross-Sectional Study in Nigeria. Journal of Datta Meghe Institute of Medical Sciences University, 2025. 20 (2): p. 364-372. Patamatamkul, S., S. Kanogtorn, and O. Putcharoen. P-580. A randomized controlled trial evaluating virologic and renal outcomes after switching from TDF/FTC/EFV to TDF/3TC/DTG (TLD) versus DTG+ 3TC in virologically suppressed Thai PWH–a pilot study . in Open Forum Infectious Diseases . 2025. Yazie, T.S., et al., Chronic kidney disease among people living with HIV on TDF based regimen: A systematic review and meta-analysis. Plos one, 2025. 20 (2): p. e0318068. Asirvatham, E.S., et al., A review of Tenofovir Disoproxil Fumarate associated nephrotoxicity among People Living with HIV: Burden, risk factors and solutions. Clinical Epidemiology and Global Health, 2024. 25 : p. 101462. Gupta, S.K., et al., Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. Aids, 2019. 33 (9): p. 1455-1465. O'Rourke, J., et al., Effectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review. Journal of the International AIDS Society, 2023. 26 (2): p. e26037. Additional Declarations No competing interests reported. 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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-9091584","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":609063949,"identity":"e17aa09b-3af7-4661-9d7e-6fc215a32b00","order_by":0,"name":"Esther M Nasuuna","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYDADfmYGgwOkaZFsJlkLUL0Bke6Rbn78mbftjrzxceaNBxhqbBgMzi8g4J45x8ykedueGW47zFZwgOFYGoPBjQcE3HMjwYyZt+0w47bDPAYHGBsOA0UO4NdifyP9M9Bhh+03NxOrxUAixwDosMOJG5hhWs434NcicSOnTHLOucPJM0B+STiWxiN5A78OBv4Z6Zs/vCk7bNvff3jzhw81NnJ85wk4DBUkMDDwMEgkkKIFYjFJtoyCUTAKRsEIAACPakbYGd8UvQAAAABJRU5ErkJggg==","orcid":"","institution":"Non-communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit","correspondingAuthor":true,"prefix":"","firstName":"Esther","middleName":"M","lastName":"Nasuuna","suffix":""},{"id":609063950,"identity":"32c5b761-4290-4c0d-8424-abb1a774b876","order_by":1,"name":"Risa Hoffman","email":"","orcid":"","institution":"David Geffen School of Medicine, University of California Los Angeles","correspondingAuthor":false,"prefix":"","firstName":"Risa","middleName":"","lastName":"Hoffman","suffix":""},{"id":609063952,"identity":"96f99071-93c8-448a-97eb-bb9a3d6bc0a7","order_by":2,"name":"Robert Kalyesubula","email":"","orcid":"","institution":"Non-communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Kalyesubula","suffix":""},{"id":609063954,"identity":"15df7831-20d3-4242-b3af-a64e1c0c6fce","order_by":3,"name":"Chido Dziva Chikwari","email":"","orcid":"","institution":"Biomedical Research and Training Institute","correspondingAuthor":false,"prefix":"","firstName":"Chido","middleName":"Dziva","lastName":"Chikwari","suffix":""},{"id":609063956,"identity":"b91792e9-e6d7-4398-b4d3-d36af4f2e8ba","order_by":4,"name":"Helen A Weiss","email":"","orcid":"","institution":"MRC International Statistics and Epidemiology Group, London School of Hygiene \u0026 Tropical Medicine","correspondingAuthor":false,"prefix":"","firstName":"Helen","middleName":"A","lastName":"Weiss","suffix":""}],"badges":[],"createdAt":"2026-03-11 07:54:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9091584/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9091584/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105040029,"identity":"13417376-377b-4ac5-9b98-58c9288ea1e0","added_by":"auto","created_at":"2026-03-20 07:47:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":568095,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9091584/v1/6a668785-8c96-48f8-bef0-67250f482a69.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Kidney Dysfunction In Young People Living With HIV On Dolutegravir-Based Regimens In Kampala, Uganda","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAntiretroviral therapy (ART) has transformed HIV infection from a fatal illness into a chronic condition [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The success of ART means that young people living with HIV (YPLHIV) are increasingly surviving into adulthood and face long-term health challenges [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Non-communicable conditions, including chronic kidney disease, have emerged as important contributors to morbidity and mortality [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Multiple factors \u0026mdash;direct effects of HIV, coexisting infections, traditional risk factors (hypertension and diabetes), and exposure to nephrotoxic ART\u0026mdash; drive kidney dysfunction in YPLHIV [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Young people are especially vulnerable because they are likely to be exposed to ART for many decades, during which cumulative drug effects and ongoing HIV-related immune activation may increase the risk of kidney dysfunction [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe recent global transition to dolutegravir (DTG)-based regimens has introduced new complexities in monitoring kidney function. DTG is now the preferred first-line ART in many low- and middle-income countries, including Uganda, because of its high efficacy and favourable tolerability profile [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, DTG inhibits tubular secretion of creatinine without affecting glomerular filtration, leading to modest but persistent increases in serum creatinine [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This pharmacological effect may confound the assessment of kidney function and obscure early signs of true kidney impairment. There is a critical need to characterise the burden of kidney dysfunction in YPLHIV on DTG-based ART in Uganda. We set out to describe the prevalence and association of kidney dysfunction with DTG-based regimens among YPLHIV in Uganda.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e We conducted a cross-sectional study in seven urban public health facilities in Kampala, Uganda, which provide comprehensive HIV care and treatment services, mostly for the urban poor.\u003c/p\u003e \u003cp\u003eThe study included YPLHIV aged 10\u0026ndash;24 years with presumed perinatal HIV infection. Pregnant YPLHIV were excluded. Systematic random sampling (listing all YPLHIV in the clinics and picking out every other name) was used to identify potential participants. These were invited to join the study. Details of the parent study have been published previously [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEligible participants were invited to the HIV clinic through a phone call to those above 18 years or the caregiver for those below 18 years. They were screened, consented, and enrolled. We collected urine samples for the albumin creatinine ratio (ACR), proteinuria on dipstick, and blood samples for serum creatinine and cystatin C. We estimated glomerular filtration rate (eGFR) using the CKDEPI 2021 equation or the Bedside Schwartz (\u0026lt;\u0026thinsp;18 years).\u003c/p\u003e \u003cp\u003eParticipants were interviewed to collect socio-demographic data such as age, sex, and socioeconomic status. Measurements were taken for weight, height, mid-upper arm circumference (MUAC), body mass index (BMI) was calculated as weight over height squared. Stunting was calculated according to the WHO standards [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Muscle mass was determined using a bioimpedance machine and calculated using sex and age-specific cut-offs.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eData management and statistical analysis\u003c/strong\u003e \u003cp\u003eData were collected in REDCap and analysed with STATA statistical software Version 18 (STATA Corp USA). Demographic and clinical data were summarised in percentages or means (standard deviation [SD]) and median (interquartile range [IQR]). We used chi-square tests to compare kidney function parameters of participants on tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and DTG compared with those on DTG combined with other Nucleoside Reverse Transcriptase Inhibitors, such as zidovudine or abacavir, and 3TC (other DTG regimens).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical considerations\u003c/strong\u003e \u003cp\u003e Ethical approval was received from the Uganda Virus Research Institute (UVRI) Research Ethics Committee (reference number GC/127/946), the Uganda National Council of Science and Technology (HS2578ES) and the London School of Hygiene and Tropical Medicine institutional review board (28797). All participants aged 18 years or older provided written informed consent. Those aged\u0026thinsp;\u0026lt;\u0026thinsp;18 years, provided written participant assent, and caregiver consent. All participants with suspected CKD were referred to a nephrologist for management.\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOut of 500 YPLHIV, 483 were enrolled into the study, with 367 (76%) on TDF/3TC/DTG and 116 (24%) on other regimens. There were slightly more females than males in both groups. There were more underweight participants on the non-TDF-containing DTG regimens. Viral suppression, mean duration on ART, and muscle mass were similar in both groups. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\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 the participants by ART regimen\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eMean Age in years (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTDF/DTG N\u0026thinsp;=\u0026thinsp;367\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOther/DTG\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;116\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0 (3.5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.4 (3.4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e10 to 17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e231 (62.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (80.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e18 to 24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (19.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e211 (57.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62 (53.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eSocioeconomic status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLowest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129 (35.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (37.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114 (31.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (30.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHighest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (33.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (31.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e224 (61.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (37.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eUnderweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106 (29.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67 (57.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOverweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eStunting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNot stunted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e221 (84.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (79.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eStunted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (20.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eMid upper arm circumference\u0026nbsp;(MUAC)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e338 (92.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 (86.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalnourished\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e28 ( 7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e51.2 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.9 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003e \u003cem\u003eMalnourished participants had a MUAC in either yellow or red.\u003c/em\u003e \u003c/p\u003e\n\u003ch3\u003eParticipants' kidney parameters by regimen\u003c/h3\u003e\n\u003cp\u003eThe mean serum creatinine levels were higher among participants on TDF/DTG compared to those on other DTG-based regimens without TDF, although the mean eGFR and the proportions with eGFR\u0026thinsp;\u0026lt;\u0026thinsp;90 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e were similar. The mean cystatin C was similar in both groups. The mean eGFR was within normal limits and lower among those on TDF/DTG compared to those on other DTG-based regimens. Although the proportion with eGFRcystc below 90ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e was higher among those on DTG-based regimens without TDF compared to those on TDF/DTG, this was not significant. The proportion of YPLHIV with ACR\u0026gt;30mg/g was higher among those on other DTG-based regimens, and proteinuria proportions were high but similar (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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\u003eParticipant kidney parameters by ART regimen\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTDF/DTG\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;367\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOther DTG-based* N\u0026thinsp;=\u0026thinsp;116\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine Mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.68 (0.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.59 (0.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR serum creatinine (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118.8 (19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113.9 (20.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR serum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;90ml/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e317 (87.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (89.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;90ml/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCystatin C Mean(SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.81 (0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.81 (0.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR cystatin C (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114.2 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116.5 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR cystatin C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbove 90ml/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e212 (58.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (52.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBelow 90ml/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e151 (41.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (47.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin creatinine ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBelow 30mg/g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e328 (90.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (87.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbove 30mg/g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e263 (71.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (69.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (30.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Regimens with either abacavir or zidovudine together with lamivudine and dolutegravir.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur data suggest a high prevalence of kidney dysfunction (based on eGFR cystatin C below 90ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e and proteinuria) among YPLHIV compared to youth who are not living with HIV, which is not associated with DTG/TDF versus other DTG-based regimens.\u003c/p\u003e \u003cp\u003eOur findings are consistent with those of the ODYSSEY trial from Uganda, Thailand, Europe, Zimbabwe, and South Africa, which reported no kidney-related adverse effects in 707 children and adolescents living with HIV on DTG-based regimens coupled with NRTIs, including TDF at 96 weeks [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. A systematic review on the efficacy and safety of DTG among children and adolescents reported data on 11 studies, which did not report any kidney-related adverse events, although the number of children on both DTG and TDF and the duration were not reported [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Taken together, these data are reassuring about ongoing use of DTG combined with TDF as first-line ART for YPLHIV initiating treatment in Uganda [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are concerns about DTG obscuring kidney dysfunction, especially when it is co-administered with TDF, which is known to cause kidney dysfunction [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This concern has not yet been fully addressed, as there are very few studies done in Africa that involve young people living with HIV on both DTG and TDF [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A study done in Nigeria among 170 adult PLHIV found that those on TDF/DTG had impaired kidney function [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A pilot clinical trial showed that PLHIV who switched to TDF/DTG combination had a greater decline in eGFR compared to those switched to DTG/lamivudine [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A global systematic review and meta-analysis showed a 7% prevalence of chronic kidney disease among those treated with TDF, there was no mention of DTG effects [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Since the duration on ART is associated with risk of TDF kidney toxicity [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and YPLHIV are exposed to TDF for a longer time than adults living with HIV, vigilant monitoring of kidney function is warranted for YPLHIV treated with TDF-containing regimens, to ensure early diagnosis. Use of tenofovir alafenamide (TAF) should also be considered, as this is associated with less kidney toxicity compared to TDF, according to data pooled from 26 clinical trials that also included children [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, weight and metabolic changes should be monitored [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe main limitation of our study was the inability to compare the kidney function of YPLHIV on DTG based regimens to others who were not exposed to DTG, since most YPLHIV were switched to DTG following the WHO recommendations. We did not account for the regimen changes over time with the changing recommendations over the lifetime of the YPLHIV. It was also a cross-sectional study, and more information about long-term toxicity should be collected from longitudinal studies. The strengths are that the study was adequately powered to detect an association, and our findings are generalisable to YPLHIV living in settings similar to ours.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe found that YPLHIV on DTG-based regimens had a high prevalence of proteinuria and elevated ACR regardless of the nucleoside analogues utilized alongside DTG. However, eGFR calculated from both serum creatinine and cystatin C was largely within normal limits. Longer-term follow-up is needed to understand whether YPLHIV will develop chronic kidney disease as they age, and to elucidate risk factors for kidney disease progression, including safer long-term ART regimens.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlbumin Creatinine Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eART\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAnti-Retroviral Therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody Mass Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic Kidney Disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCKD-EPI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic Kidney Disease Epidemiology Collaboration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDTG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDolutegravir\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEstimated Glomerular Filtration Rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHuman Immunodeficiency Virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterquartile Range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKDIGO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKidney Disease Improving Global Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMUAC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMid upper arm circumference\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard Deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSub-Saharan Africa\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited States of America\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eYPLHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eYoung People Living with HIV\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Uganda Virus Research Institute (UVRI) Research Ethics Committee (GC/127/946), the Uganda National Council of Science and Technology (HS2578ES), and the London School of Hygiene and Tropical Medicine (reference 28797) approved this study. \u0026nbsp;All participants regardless of age provided informed consent/assent after provision of age-appropriate study information. Participants \u0026gt;18 years s provided a written informed consent. Children \u0026lt;18 years provided written assent, and their caregivers provided a written informed consent. The studies were conducted in accordance with the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo protect the confidentiality of the participants who provided the clinical data, the data that support the findings of this study are available from the corresponding author upon 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\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupport for the studies was provided by Fogarty International Centre, National Institutes of Health (grant #2D43TW009771-06) HIV and co-infections in Uganda.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEsther Nasuuna, \u0026nbsp; Doctoral Research Fellow, NIHR131273 is funded by the NIHR for this research project. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care.\u003c/p\u003e\n\u003cp\u003eThe funders had no role in the study design, collection, analysis or interpretation of data. Neither did they choose where this work gets published.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEN, RH, CD, HW contributed to the conceptualization and design of the study, data collection, analysis, interpretation, and editing the manuscript. EN, RH and HW drafted the manuscript. RK \u0026nbsp;contributed to the interpretation of results and edited the manuscript for important scientific content. All authors reviewed and approved the manuscript before submission for publication. All authors are accountable for the work in this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe wish to acknowledge the participants, their caregivers and the facility staff where this study took place. We also acknowledge the study team, Miss Evelyn Natuha, Miss Stella Mirembe and Mr. Malcolm Lwanga. We acknowledge the KCCA leadership and the PEPFAR program that supports HIV care for the YPLHIV.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eFrigati, L.J., et al., \u003cem\u003eChronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy.\u003c/em\u003e The Lancet Child \u0026amp; Adolescent Health, 2020. \u003cstrong\u003e4\u003c/strong\u003e(9): p. 688-698.\u003c/li\u003e\n \u003cli\u003eFrigati, L.J., et al., \u003cem\u003eMultisystem impairment in South African adolescents with Perinatally acquired HIV on antiretroviral therapy (ART).\u003c/em\u003e Journal of the International AIDS Society, 2019. \u003cstrong\u003e22\u003c/strong\u003e(8): p. e25386.\u003c/li\u003e\n \u003cli\u003eSwanepoel, C.R., et al., \u003cem\u003eKidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.\u003c/em\u003e Kidney international, 2018. \u003cstrong\u003e93\u003c/strong\u003e(3): p. 545-559.\u003c/li\u003e\n \u003cli\u003eBhimma, R., M.U. Purswani, and U. Kala, \u003cem\u003eKidney disease in children and adolescents with perinatal HIV‐1 infection.\u003c/em\u003e Journal of the International AIDS Society, 2013. \u003cstrong\u003e16\u003c/strong\u003e(1): p. 18596.\u003c/li\u003e\n \u003cli\u003eworld Health Organization, \u003cem\u003eUpdated recommendations in first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV\u003c/em\u003e. 2018, World Health Organisation: Netherlands.\u003c/li\u003e\n \u003cli\u003eCattaneo, D. and C. Gervasoni, \u003cem\u003eNovel Antiretroviral Drugs in Patients with Renal Impairment: Clinical and Pharmacokinetic Considerations.\u003c/em\u003e European Journal of Drug Metabolism and Pharmacokinetics, 2017. \u003cstrong\u003e42\u003c/strong\u003e(4): p. 559-572.\u003c/li\u003e\n \u003cli\u003eNasuuna, E.M., et al., \u003cem\u003eComparison of the prevalence and associated factors of chronic kidney disease diagnosed by serum creatinine or cystatin C among young people living with HIV in Uganda.\u003c/em\u003e BMC nephrology, 2024. \u003cstrong\u003e25\u003c/strong\u003e(1): p. 422.\u003c/li\u003e\n \u003cli\u003eWHO Multicentre Growth Reference Study Group, \u003cem\u003eWHO Child Growth Standards based on length/height, weight and age.\u003c/em\u003e Acta Paediatr Suppl, 2006. \u003cstrong\u003e450\u003c/strong\u003e: p. 76-85.\u003c/li\u003e\n \u003cli\u003eTurkova, A., et al., \u003cem\u003eDolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children.\u003c/em\u003e New England Journal of Medicine, 2021. \u003cstrong\u003e385\u003c/strong\u003e(27): p. 2531-2543.\u003c/li\u003e\n \u003cli\u003eTownsend, C.L., et al., \u003cem\u003eEffectiveness and safety of dolutegravir and raltegravir for treating children and adolescents living with HIV: a systematic review.\u003c/em\u003e Journal of the International AIDS Society, 2022. \u003cstrong\u003e25\u003c/strong\u003e(11): p. e25970.\u003c/li\u003e\n \u003cli\u003eKouamou, V., et al., \u003cem\u003eTenofovir, Lamivudine, and Dolutegravir Among Rural Adolescents in Zimbabwe: A Cautionary Tale.\u003c/em\u003e AIDS Research and Human Retroviruses, 2022. \u003cstrong\u003e38\u003c/strong\u003e(10): p. 774-778.\u003c/li\u003e\n \u003cli\u003eDiack, A., et al., \u003cem\u003eProgressive Decline of the Glomerular Filtration Rate in HIV-infected Children Treated With Tenofovir Disoproxil Fumarate-based Regimens in West and Central Africa.\u003c/em\u003e The Pediatric infectious disease journal, 2020. \u003cstrong\u003e39\u003c/strong\u003e(8): p. 737-739.\u003c/li\u003e\n \u003cli\u003eMtisi, T.J., et al., \u003cem\u003eTenofovir-associated kidney disease in Africans: a systematic review.\u003c/em\u003e AIDS research and therapy, 2019. \u003cstrong\u003e16\u003c/strong\u003e(1): p. 12.\u003c/li\u003e\n \u003cli\u003eOdegbemi, O.B., et al., \u003cem\u003eRenal Function and Nephrotoxicity Assessment in People Living with HIV on Tenofovir, Lamivudine, and Dolutegravir Therapy: A Cross-Sectional Study in Nigeria.\u003c/em\u003e Journal of Datta Meghe Institute of Medical Sciences University, 2025. \u003cstrong\u003e20\u003c/strong\u003e(2): p. 364-372.\u003c/li\u003e\n \u003cli\u003ePatamatamkul, S., S. Kanogtorn, and O. Putcharoen. \u003cem\u003eP-580. A randomized controlled trial evaluating virologic and renal outcomes after switching from TDF/FTC/EFV to TDF/3TC/DTG (TLD) versus DTG+ 3TC in virologically suppressed Thai PWH\u0026ndash;a pilot study\u003c/em\u003e. in \u003cem\u003eOpen Forum Infectious Diseases\u003c/em\u003e. 2025.\u003c/li\u003e\n \u003cli\u003eYazie, T.S., et al., \u003cem\u003eChronic kidney disease among people living with HIV on TDF based regimen: A systematic review and meta-analysis.\u003c/em\u003e Plos one, 2025. \u003cstrong\u003e20\u003c/strong\u003e(2): p. e0318068.\u003c/li\u003e\n \u003cli\u003eAsirvatham, E.S., et al., \u003cem\u003eA review of Tenofovir Disoproxil Fumarate associated nephrotoxicity among People Living with HIV: Burden, risk factors and solutions.\u003c/em\u003e Clinical Epidemiology and Global Health, 2024. \u003cstrong\u003e25\u003c/strong\u003e: p. 101462.\u003c/li\u003e\n \u003cli\u003eGupta, S.K., et al., \u003cem\u003eRenal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials.\u003c/em\u003e Aids, 2019. \u003cstrong\u003e33\u003c/strong\u003e(9): p. 1455-1465.\u003c/li\u003e\n \u003cli\u003eO\u0026apos;Rourke, J., et al., \u003cem\u003eEffectiveness and safety of tenofovir alafenamide in children and adolescents living with HIV: a systematic review.\u003c/em\u003e Journal of the International AIDS Society, 2023. \u003cstrong\u003e26\u003c/strong\u003e(2): p. e26037.\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":"aids-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arty","sideBox":"Learn more about [AIDS Research and Therapy](http://aidsrestherapy.biomedcentral.com/)","snPcode":"12981","submissionUrl":"https://submission.nature.com/new-submission/12981/3","title":"AIDS Research and Therapy","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Kidney function, dolutegravir, young people living with HIV, Sub Saharan Africa","lastPublishedDoi":"10.21203/rs.3.rs-9091584/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9091584/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe assessed the association between dolutegravir (DTG)-based antiretroviral therapy and kidney abnormalities among young people living with HIV aged 10–24 years in Kampala, Uganda. In this cross-sectional study, albumin–creatinine ratio (ACR), proteinuria, and estimated glomerular filtration rate (eGFR) were measured. Among 483 participants, 78% received tenofovir (TDF)/DTG. Mean serum creatinine was higher and creatinine-based eGFR lower among those on TDF/DTG, while cystatin C and cystatin C–based eGFR were similar. The prevalence of elevated ACR, proteinuria, and eGFR \u0026lt;90 ml/min/1.73m² was similar. Kidney abnormalities were common, supporting the need for longitudinal studies to clarify chronic kidney disease risk\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Kidney Dysfunction In Young People Living With HIV On Dolutegravir-Based Regimens In Kampala, Uganda","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-20 07:35:40","doi":"10.21203/rs.3.rs-9091584/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-05T01:00:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-03T08:38:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-28T19:27:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"281491288037245475811165130388699737722","date":"2026-03-20T09:25:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"57234796025596576334083072516711719348","date":"2026-03-19T18:02:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141272357822444355009542497606289281376","date":"2026-03-18T04:45:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-17T23:27:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-17T10:33:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"AIDS Research and Therapy","date":"2026-03-17T09:25:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"aids-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arty","sideBox":"Learn more about [AIDS Research and Therapy](http://aidsrestherapy.biomedcentral.com/)","snPcode":"12981","submissionUrl":"https://submission.nature.com/new-submission/12981/3","title":"AIDS Research and Therapy","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5c5b77bc-f2c6-4dbd-85e6-129f78a77535","owner":[],"postedDate":"March 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T02:09:50+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-20 07:35:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9091584","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9091584","identity":"rs-9091584","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}